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The RECOVERY Trial Reports on Hydroxychloroquine

The recent implosion of the Surgisphere data papers has been big news. It included one that purported to show no benefit (and actual harm) from hydroxychloroquine treatment, and even more harm when combined with azithromycin – but since the authors have been unable to back up the raw data on this, the paper cannot be taken as valid.

This has some people thinking that there is therefor no case against using HCQ, and indeed, that the case against it has collapsed. Keep in mind, though, that even before the Lancet paper the evidence for it as a useful coronavirus treatment was thin and equivocal. And it’s been noted by many in the last few days that there are well-controlled trials underway with hydroxychloroquine, whose data will read out and tell us a lot more.

Well, one of them has. The RECOVERY trial is a large effort in the UK to evaluate several potential therapies, and today its organizers announced results from an evaluation of the hydroxychloroquine treatment arm:

Image

And there, I think, we have it. Martin Landray of Oxford, a leader of the trial, told ReutersThis is not a treatment for COVID-19. It doesn’t work” I think I agree with him. And no, I don’t think that there is a sudden switchover to efficacy when zinc is added, but you know what? We’ll be getting trial data on that idea, too. Unless there is some dramatic news, a possibility that I would not put money on, I do not plan to revisit the topic of hydroxychloroquine on this site. There are too many other more worthwhile things to talk about. I’ll update this post if needed, but that’s probably going to be it.

231 comments on “The RECOVERY Trial Reports on Hydroxychloroquine”

  1. colintd says:

    Thanks for reporting what appears to be a well run, well powered test of this “treatment”, and the “no benefit” result.

    As you say there are bound to be those who will say “why didn’t they include x or y” or “why didn’t they only give doses when Mars was below the horizon”, but I have to say there are other much more interesting things I’m much rather you wrote blogs on.

    Keep up the good work.

    1. colintd says:

      Did you provide a commentary on the other reported RECOVERY trial which I have missed? https://www.recoverytrial.net/files/recovery-and-remdesivir-v1-0-2020-05-27-1.pdf

      If not, I’d be interested to hear your views

    2. george j says:

      Again,
      the effectiveness of the drug is at the onset of symptoms with Zinc. Not while in hospital spiraling into ARD or Pre ARD state.

      1. Tia says:

        Where is your study or sources showing this is true? Care to share?

        1. Yukidongo says:

          I am a ventilator nurse in the US. It works. It works prophylactically, as well. I’ve “seen” it work. I could post Fauci’s release in the 2005 Virology Journal, and there are recent studies. Given early it is 100% effective. Given after you send someone home to isolate, or to someone who didn’t come in because they were terrified of dying on a vent with “killer” PEEP(they don’t even pretend…a PEEP of 25 will kill you…(NY)
          Back to efficacy: EARLY TO MODERATE symptoms, shortness of breath to “clawing for air”, fever, pain, malaise are usually decreased significantly if not non-existent starting in 6-12 hours. Do your own research. Don’t use Google. There are 51 (+) studies globally. 16 (-)…6 of those retracted, and 10 “late stage”. The reason for stopping HCQ was to gain control. When have you ever heard of Pharmacy Boards lining up against doctors? The drug is safe “on anti-malarial label” for pregnant women, nursing mothers, infants, and children. 4x the highest dose amount allowed, was given to create the possible side effects people are reading about. Prophylactically, 1-2 tablets per week, 200mg, stops infection. 250mg twice a day for 5 days with zinc and doxycycline, or zithromax is the treatment. The first days dosing is higher, if the symptoms are more severe. HCQ works because this virus attacks the longs first, and the drug terms to maintain its higher levers there to kill it (simple version, so many other pharmacological reasons). Btw… Here’s the FAUCI RELEASED STUDY… PENNIES TO TREAT. Remdesivir is 1600.00 a dose. The monoclonal DNA altering vaccine they’re wanting to use cannot be reversed once given a bad reaction or vaccine damage…you’re done.
          No need for any of that if they just start using HCQ like the rest of the world is using it.

        2. Lauraok says:

          Much success in early treatment
          https://c19study.com/

          1. JasonP says:

            Nice table of results!

            Which of those papers is a ‘gold standard’ study? i.e. Randomized Controlled Trial (RCT)?

            I saw a few retrospective studies, some in vitro (test tube) studies but none that stated they were RCTs. Unfortunately anecdotal evidence or less than gold standard studies is not going to convince or change the minds of the scientific types here.

            If I have this right (?) there are various types of medical “data” or studies that one can run across:

            in vitro > animal studies > case reports > retrospective studies > open label studies > RCTs

            As one moves from left to right on this list, the evidence from the study gains in credibility and strength. Problem is the primary readership here are those in the drug discovery industry and their experience suggests that many failures can and will happen, until one has locked down proof in an RCT.

            So the debate will go on, with those who use the lesser forms of evidence on one side, and the scientific community wanting to see RCT data on the other side. If we get a RCT that is appropriately powered that demonstrates efficacy, then minds could change here.

            I’m just saying.

          2. Pat says:

            Beautiful graphic. Sharing with MDs!

    3. Paul says:

      Yes, it should also be noted that the RECOVERY trial did have some participants (~15%) who took Zinc supplements (both on the HCD and placebo sides). No significant effect was seen.

      1. S crashy says:

        How can we see that 15% took zinc, i cannot see where that is located

    4. ol' bonespurs says:

      Down in the bunker
      Making HCQ great again
      No courtesy flush

      1. chris a glynn says:

        awesome

    5. Philippe says:

      This article failed to mention that they used dangerous doses of HCQ. 2400mg in the first 24 hours and 9600mg in 10 days. Plenty of government agencies all over the world set the limit/day to 600mg. 4 times the limit
      Malaria chock treatment is 800mg in the first day and 2000mg total in 48 hours. Because agencies know the half life of HCQ is 22 days.
      The conclusion made is misguiding and should be changed.

      1. Elie j. Chazarenc says:

        Stop bullshit

      2. Lorraine says:

        I wonder who guided the original studies to overdose patients with 2400mg of Hydroxychloriquin vs the less harmful than aspirin dose of 200mg twice per week, within 48hrs. Then the additional 9600 within 10 days? Lancet Papers were retracted on June 4, 2020.The study which lead the ban, used information gathered from 671 hospitals around the world and the medical records of 96,000 patients. If so many died from the overdose recommendation from “experts” shouldn’t someone be held responsible for “misinformation” also? Just a thought.

      3. Carla R Miller says:

        The people I know who have benefited from taking HCQ/zinc/antibiotics are taking 200 mg HCQ and zinc just over the counter w/antibiotics as prescribed. A friend who is a doctor’s wife was able to get it after she tested positive. She was better w/in hours. have you seen this? https://www.youtube.com/watch?v=KbRxtrZzjVs&fbclid=IwAR3APYY0eNspfh9mrXJM9xVNg1Xixbw_fplok0vGum1-FsoRSKXuogcAjlo also have you updated with the results from Ford Foundation study? https://www.detroitnews.com/story/news/local/michigan/2020/07/02/michigan-henry-ford-health-study-finds-hydroxychloroquine-lowers-covid-19-death-rate/5365090002/?fbclid=IwAR3c3gOtnIMrEEeoVSJXZrJhvrvnjMO34x3ysnAGNuHYPteCB-Xpq2qkOjI I did see where someone else posted about Ford Foundation.

        1. Derek Lowe says:

          That’s not a Ford Foundation study. It’s from a hospital system named “Ford”. And if you look at the actual numbers, you will see that the group given the HCQ was younger than the control group, and more likely to get dexamethasone as well.

      4. Yukidongo says:

        Exactly. 4x the highest dose allowed, and over a period longer than 5 days.

    6. ROBERT DAMON says:

      It turns out that the company doing the study, Surgisphere is a scam, a front piece owned by a science fiction writer with no medical background. Why wasn’t this picked up on by our strangely unobservant media?

      1. Yukidongo says:

        I wouldn’t be positive, but that is on of two I think I read HAD TO RETRACT their studies. Several aren’t even studies, they’re just data collection botched with bias and assumption…ad the VA Director explained about the study (also retracted now) of the VA stats. No co-morbidities were considered, or the severity of the illness, or even the fact that these people were mostly not even positive for COVID, and the HCQ was being used off label…those charts were from before COVID, and the data gathered within days of Trump suggesting HCQ would work. Agent Orange, malaria, emphysema, diabetes, Alzheimer’s, Congestive Heart Failure, Pulmonary fibrosis 2° to Abestosis… and finally, age 78 and older. People need to learn how to do research, and not watch the news.

    7. Fran OKeefe says:

      HCQ works if it is used early and it works to prevent it to those exposed if taken the first few days after exposure. There is NOT 1 legit study that proves it doesn’t work early. Every negative study is either flawed or worse fraudulent. The VA study looked back at people who were basically dead when they received it. The Lancet study was a scam. The others either use it too late and or use too high dosage. The evidence is overwhelming. If you don’t see it, it is because you don’t want to see it. Here is a site that has about every study done to date and the only conclusion is alot of people are dying needlessly!

      https://c19study.com/

      1. Scott says:

        Whenever I see a study that purports to put the nail in the coffin of HCQ treatment, they have all been large dose and/or hospitalized/very sick patients. THAT’S THE WRONG WAY TO USE IT! Jeez.

    8. William Naughton says:

      Sorry, the Recovery Study really sounds suspicious – here’s why:

      On their Results page (link below) referencing HCL:
      “This is not a treatment for COVID-19. It doesn’t work” I think I agree with him. And no, I don’t think that there is a sudden switchover to efficacy when zinc is added, but you know what? We’ll be getting trial data on that idea, too.”

      Actually, no, they already shut down the study before publishing the results “with that data”. How will they provide that “later” when its already shut down?

      So they didn’t use zinc in the study or they haven’t reported the results of that branch of the study – because they shut it down already.

      HCL acts on zinc to bloc entry of the virus to the cell…. this is common knowlege. Without zinc its like pulling the trigger on an empty gun and declaring it defective because it doesn’t have bullets. This suggests gross incompetence at best.

      One would assume better of Oxford but the Lancet and New England Journal of medicine were Both caught using obviously fraudulent behavior (from a very unsavory source) and they still published before peer review forced a retraction.

      Went to their site. Can’t find the methodology used, only their conclusions based on a process that isn’t published here. How is this supposed to be peer reviewed if they don’t even put the process on their website.

      https://www.recoverytrial.net/results/hydroxychloroquine-results
      Good luck finding anything to peer review here.

      That fact that they didn’t use zinc clearly indicates that they somehow aren’t aware of how it works. HCL deposits zinc at the receptor sites on the cell wall where the virus enters the cells, blocking its entry and thus its replication….How is it even possible at this late stage that they don’t see why zinc is required? How can they possibly be qualified to conduct this trial when they clearly don’t know how to administer the drug or how it works?

      Show the work…. or retract your “Results”.
      I suspect this study, as the other two would be in the dumpster if they did.

      This “study” really, really needs to be peer reviewed.
      They discontinued it, they claim it didn’t work and they Don’t publish what they did????

      How is that a study at all?

      1. Derek Lowe says:

        Here, read the complete manuscript with as many details as you like: https://www.medrxiv.org/content/10.1101/2020.07.15.20151852v1

      2. Thomas says:

        Lots of things that work in vitro do not work on sick people. Frustrating but it is the way it is.
        I assume because they are not attacking a rate-limiting step in the disease. Or the effect is balanced because the body compensates with one of its feedback systems.
        It is very common. It is no miracle to find something that hits a screen.
        And if it worked well, it would have been seen much above anecdotal levels.

    9. Clint Gurnsey says:

      2000mg of Hydroxychloroquine in the first 12 hours is a toxic load of Hydroxychloroquine as stated in the 1979 H. Weniger WHO funded study.

    10. MARY Ann Dowrick says:

      What was the dosage of hcq given to hospitalised patients in the Recovery study? Why isn’t it published any where?

  2. SirWired says:

    I’ve said it before, and I’ll say it again: For a drug combo that was alleged to be a “Game Changer” the benefits (if any) sure have been awfully hard to spot.

    1. James Burke says:

      https://pdf.sciencedirectassets.com/312001/AIP/1-s2.0-S2052297520300615/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEIb%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEaCXVzLWVhc3QtMSJIMEYCIQDtL9OW8KbZ5w5XukOy8q%2B0pcR%2FEcTHrOLR2Iy2QKQBugIhALuzdHt7fiHqiVCCnhgET8vDaUPQM6Gow49dKKe%2BXiUGKr0DCO%2F%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQAxoMMDU5MDAzNTQ2ODY1Igxo26khwIjby6v2jiIqkQM2kquUAjDRtaK%2Bqaal0uKBgTow55ZS1nCihTvIZp2pUeSKdMCxOXZ%2FFH414spgsheF3z7SfRGChx%2Bhi50OlXb6hwaQ5PQJkWc0g%2FOhL4gkaUidLfAkyz7f8ac9y9twW1YMqsgkAoOWn9NeNXDvMyIAo6MlzARjlSk%2BVT7wHZe7zPMkkY7ujYiq9w30vGd4Ydw5VUtleljdlL6HxuB7kFNFeBE%2FGs0Pq6Fykch4Qst8%2FjDRNZHeyTWvnRNuVFvfRLhgfOJRHDvh2lMQDPH4Txi%2B51fuNZMw1ckkfG4AyPryklA04LFqCwDbwbOyjT5x9tL47A4IZDu5NoQC%2B%2BcTdA%2FDFma9RnPUOi1bKnRz6nymyf%2BVIXq%2B2slsvEexaH9EUhKYiFwDL1fgNG7ENoi6gQygXrHMLql5RGRK2QjgckLaZaov5Xa1zjs%2BH%2BX6TFXzJ9%2F4VMe79GQhkx1hcsL%2FqMKIWo%2FBfa%2BBPuzVl1rJ4V20BoMpz6I04J5JMjlNJDYpiGE8vLE4ht42Nx5wo9ZzQR89FDCChvn2BTrqAbkihqyIdQVgMHQkdFuH%2BC9DpZ%2F14fjNPlgclskLLP4G8FQP5c1jPljHBHAQO%2Bi8cbM%2BFn68dlyF7ysyLhxIHXjVVV3G1ghrCxVINdrp5brdNVJewAQU105OzDZuHE%2FCMwEK3rVJ49eC38LEoRQv5SqTAqv69Wo9AE88Jg9l7I8alo%2BPg3gft63EZ%2FEQC%2BVKiJSSYo5mT09R20M8aUJj6T1BSAagq4%2BB8HuS0oM3UQ%2BcUOWn9VqGecalJ330sOtbvR0%2F%2FZVo50FBVOLP3QiG2F53CcEMoyNghNwaS%2FtALXWXj3tLzLInuXbEUg%3D%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20200608T143651Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTYTDWQTHWQ%2F20200608%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=d95299e095478e2be848ca6d9d9ae01d535d956078efa73e50e3362adc88e1a9&hash=92e6933cbb15f2d219eb74a3803bfe026e1622644924e748f8641f462373236f&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S2052297520300615&tid=spdf-62715a2b-13bd-45e7-8892-d4c3e808e073&sid=93878d8f83fd624cf49826c46c766885f855gxrqa&type=client

      1. Brian Lintz says:

        Dude, tinyurl.com

    2. MARY Ann dowrick says:

      Hcq was never intended for hospitalised patients. It is too late to administer the drug then. Instead, it is meant for early, outpatient, symptomatic at risk patients to PREVENT them going into hospital.
      How hard was that to figure out?

  3. moist_towel says:

    It’s going to take a sizeable amount of cognitive dissonance to ignore that the inital data could hardly have been handled worse by some prominent figures. But by now I’m sad to say I won’t be surprised.

  4. WustlMed says:

    Look forward to the data. Mortality rate of 1/4 is higher than I thought.

  5. Quill McGee says:

    Jesus! 23% mortality rate with usual care? Conditional on hospitalization, sure, so we’re filtering for the severely sick already, but that’s still much higher than I would have guessed.

    1. tollis says:

      recovery: doses of hydroxychloroquine given to patients
      2400mg HCQ during the first 24h (instead of 600 mg recommended dosis)
      et 9600mg d’hydroxychloroquine for the whole session.
      according to health authority in france, a 1800 mg dosis in a day would require urgent hospitalisation .
      in other words, recovery test was designed to kill the patients.

      1. HCQ Dosing on FDA label: 600mg/day on arthritis loading; 800mg PO loading for acute treatment on malaria – the highest day one loading dose on FDA label!
        “Without a dose, there is no drug! The Cardio AE is dose related.
        HCQ has a slow mode in action, in treating chronic inflammation such as arthritis, it requires weeks induction at low dose (200mg/day). It seems that HCQ OSD may not be quicker enough to seize the fire in such acute lung failure in late stage severe critical patients with Covid 19. Again one needs to avoid using in high risks vulnerable cardio patients, especially not with Over dose ( 1200mg on loading has already exceeded FDA recommended dosage for any prior indications).

      2. Robert Clark says:

        OMG! You keep finding out something weird about these HCQ studies! The one study faked the data, then another one didn’t even test for it, then this one gives a dosage bordering on a lethal dosage of 3 gm per day!

        What is it about HCQ for COVID -19 that researchers keep making these bizarre mistakes???

        Robert Clark

        1. WST says:

          Day 1 dose 2 g
          Hydroxychloroquine by mouth for a total of 10 days as follows:
          Timing Dose
          Initial 800 mg
          6 hours after initial dose 800 mg
          12 hours after initial dose 400 mg

          24 hours after initial dose 400 mg
          Every 12 hours thereafter for 9 days 400 mg

      3. Vigneron says:

        No, 1860 mg base/1st day (12×155mg base dose).
        « So the loading dose in RECOVERY is twice the normal dose for treating malaria. However, this dose has been selected based on the available data of the IC50 for SARS-CoV-2.
        The objective is to reach plasma concentrations that are inhibitory to the virus as soon as safely possible. The plasma concentrations that will result are at the higher end of those encountered during steady state treatment of rheumatoid arthritis. Given the significant mortality in patients hospitalised with COVID-19, this dose is felt to be justified. This is the schedule that has been adopted by the World Health Organisation. No dose adjustment is required for weight based on the doses defined in this protocol. »

        1. Jonathan Betser says:

          One of Recovery trial leaders, Martin Landray has recently been interviewed by FranceSoir and asked about the HCQ dosage and he said that he used the same dosage as recommended for treating amibian dysentry. According to Professor Christian Perrone HCQ is not used for treating this disease and Dr Landray might have mistaken hydroxychloroquine with hydroxyquinolines, which could explain the wrong dosage. If that is indeed the case this study will soon be retracted, so let’s not rush into disqualifying HCQ.

          1. Jonathan Betser says:

            Amoebic dysentery* pardon my terrible spelling

          2. Some idiot says:

            Good grief, grasping for straws, to put it mildly…!

          3. theasdgamer says:

            Excellent comment! Mistakes of this kind are unacceptable and the RECOVERY paper should be withdrawn. Mistaking dosage for a completely different drug (hydroxyquinoline) used to treat amoebic dysentery with optimum dosage for hydroxychloroquine is extremely bizarre. (Pay no attention to the peanut gallery.)

          4. theasdgamer says:

            Here’s the link to the FranceSoir article about Recovery: http://www.francesoir.fr/politique-monde/recovery-trial-brexit-and-overdose

          5. David says:

            Here’s the audio interview of Martin Landray about HCQ dosage: (something fishy here)

            https://www.youtube.com/watch?v=31VEJlRyB2c

          6. Edward R says:

            Very Monty Pythonesque. Completely detached from reality. Reminds me of their Norwegian Blue parrot skit. Had to be written by Palin or Idle.

      4. Steven Thain says:

        Exactly. why is this being concealed

  6. David says:

    In a CDC case series (MMWR May 8) the fatality rate for hospitalized covid19 patients was 17%. Not too far out.

  7. psoun says:

    Glad to see real data coming forward. There are still the early treatment and pre-exposure data to contrast or close the book on this.

    Thinking aloud, is perhaps the story not HCQ (or Ivermectin) but simply the adjoining antibiotics (Zithromax, Doxycycline) themselves? There are trials on those, no?

  8. chiz says:

    Meanwhile, Elsevier’s investigation into the Raoult paper has been going for nearly two months now. They were never going to fix everything wrong with the paper and turn it into a gold plated study, at best they were going to turn it from a shitty study into a shoddy study by getting an explanation as to why patients were excluded from the analysis and so forth. But does it really take two months to sort that out? How long should we wait before we start becoming suspicious about the time it is taking?

    1. loupgarous says:

      Elsevier is one of those outfits that seems to have a surplus of insouciance about scientific rigor in papers published by its journals. I haven’t taken their imprints particularly seriously since the rash of retractions in their open access journals. If they don’t have a corporate motto yet, pecunia non olet would work.

      1. Klagenfurt says:

        De omnibus dubitandum.

  9. john says:

    Derek,

    Ok, up to you to no longer cover HCQ, of course. But I would point out that

    Neither Dr. Zelenko nor Dr. Raoult have ever advocated giving either HCQ alone, or HCQ+azithromycin, to hospitalized patients. Both emphasize the need to treat early, and also, to combine the treatment with azithromycin (R and Z) and zinc (Z, although in his latest paper, R apparently found a relationship between zinc levels and outcome).

    So again, one weakness of RCTs comes up repeatedly: is the right population being targeted? I would also point out that R has also never recommended HCQ for post-exposure prophylaxis.

    The target population would be patients over the age of 60, and younger patients with risk factors. And the treatment should be given early, and include azithromycin and probably also, zinc.

    One paper due out soon is Dr. Boulware’s second RCT treating COVID-19 patients with symptoms. The design paper is here:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205369/pdf/12630_2020_Article_1684.pdf

    His inclusion criteria for the early symptom paper are here:

    Pre-emptive therapy
    1) Non-hospitalized community-dwelling symptomatic
    (fever, cough, or shortness of breath) COVID-19
    within four days of symptom onset

    2) Coronavirus disease confirmed by reverse
    transcriptase polymerase chain reaction (RT-PCR) or
    for healthcare workers, by compatible symptoms
    following exposure to a person with a known
    positive RT-PCR result (exposure occurring within
    the past 14 days).

    The intervention is here:
    ———————————————
    1) Day 1 (upon receipt of study medicine):
    hydroxychloroquine 800 mg orally once (four
    tablets), followed six to eight hours later by 600 mg
    orally once (three tablets);

    2) Days 2 to 5: hydroxychloroquine 600 mg orally once
    daily (three tablets per day).

    So, unfortunately, this second study by Dr. Boulware will also fail to adequately test the treatment of COVID-19 that has been proposed by Drs. Zelenko and Dr. Raoult.

    Perhaps other RCTs will do this. But I don’t think that any of the RCTs so far have come even close to testing the treatments that have been reported in the two fairly large case series by Zelenko and Raoult.

    1. HA Lurker says:

      Raoult’s study did not include zinc. Zinc is Zelenko’s obsession, based on his proposed mechanism to account for Raoult’s results.

      1. Charles Shaw says:

        This study from 2014 details the interaction of Zinc and HCQ.  This isn’t new knowledge but it is being used as a political cudgel.  A recent NYU study showed a 44% reduction in death rate for patients treated with HCQ and ZINC.  When this becomes clear to the American people that 44% of those lost to this disease could have been spared, there will be a revolution. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/

        1. zero says:

          We already know the current administration gutted our country’s pandemic response mechanisms simply to spite the previous occupant of the office, but that hasn’t started a revolt. Neither would your proposition if it proves true.

          Absurd as it sounds, disease is a ‘someone else’ problem for most of us in spite of the >110k death toll. Besides, nobody sane actually believes our current leadership would do anything with a genuinely effective treatment besides try to profit from it; grifters gonna grift.

          1. Ed Dye says:

            Oh lord. We know that PRt team was NOT disbanded(gutted). You are referring to the NSC’s PRT team(2 people). the CDC’s PRT was never touched. WaPo had a great writwe-up where they gave this lie the appropriate “4 Pinocchios”.

    2. john says:

      So, instead of sniping, perhaps it might be worthwhile to suggest a proper randomized trial to test the Raoult treatment.

      1) Patient population. Nursing home patients who develop symptoms of COVID-19.
      I believe that the ideal patient population for our RCT would be nursing home patients who develop symptoms consistent with COVID-19 infection. We know that these patients are uniquely susceptible to COVID, with an expected mortality rate in the range of 20+% if they get infected. Such a high event rate is a good think in an RCT, as then it becomes easier to show an effect (as opposed to a study where the event rate is say, 10%).

      Another advantage of studying nursing home patients is, that they are easily accessible to repeat assessments, and this includes PCR testing, serum IgG/IgM antibody blood tests, and symptom assessment. As well as repeat ECG monitoring for any inordinate increase in QTc intervals. One can then do sensitivity analyses of those patients in whom symptoms were accompanied by positive IgG/IgM levels in the course of their illness.

      2) Intervention
      The treatment should include either HCQ+Azithromycin, or HCQ+Azithromycin+ Zinc. And then a control arm with usual care.

      3) Primary and Secondary Outcomes
      The nice thing about studying nursing home patients is, that the primary and secondary outcomes can be clinically meaningful. The primary outcome should be death due to any cause. Secondary outcomes could include transfer to a hospital (or palliative care unite), etc.

      So, this is the type of RCT that needs to be done. Until such a study is done, I don’t see any need to get excited about any of the other RCTs that have been reported so far.

      Maybe there is such an RCT in the planning stages or under recruitment? I couldn’t find any such, though I haven’t looked very hard.

      1. RA says:

        I agree with the idea of early-stage studying interventions in nursing homes, and think the study you propose should be done…but we should test a variety of agents in this setting, not just HCQ. I am particularly interested in early anticoagulation and immune modulation…but yes, proposed anti-virals too.

        The problems here go way beyond whether HCQ is getting a fair shake or not…we have huge, coordinated multi-national efforts for hospital treatments (when the disease is so far advanced) and vaccines (which will take time) but a disjointed, under-resourced effort for early-stage interventions. What if we had a well coordinated multi-center RECOVERY-style effort in nursing homes? This is a huge missed opportunity to learn how better to intervene at the early stages of illness.

        1. john says:

          RA:
          Good idea, to test agents in addition to HCQ, such as remdesivir.

          One problem with doing studies in nursing homes is the severe restrictions on informed consent for non-mentally competent subjects.

          But this is where the deaths are, so ideally, some RCTs, at least, should focus on this at risk population.

          Another problem is, the possible attenuation of COVID-19 that at least some observers are seeing evidence of. This may be a SARS-type of situation, where vaccine and other development had to be halted because SARS basically just went away and never came back (at least that’s how I understand it).

          This attenuation factor might also be one reason why Raoult thought that his HCQ/AZI treatment helped, comparing his good results in patients who got HCQ/AZI with earlier results in patients not on this treatment that were terrible. So, it remains possible that his stellar results were more due to viral attenuation than to a benefit of HCQ/AZI. That’s why one needs RCTs with a contemporaneous control group. But the RCTs have to be focused on the right group of patients.

          1. eub says:

            SARS didn’t go away, SARS was actively eradicated by effective public health measures.

        2. Neli Stoyanova says:

          I already saw somewhere an article about the nursing home ma where they have treated all the positive cases more than 70 with hydroxychloroquine and only one patient died

      2. WST says:

        Sorry for a comment from a non-professional. Measuring for a low probability outcomes (except of course for the nursing homes) requires enormous sample sizes. But maybe, if the antiviral hcq+azt therapy is for real, one could also check for possible less severe pulmonary issues with the CT scan. Or some other positive clinical effect for the “mild cases” ? Maybe such study could be possible as an addition to already completed observational studies?

        Italians claim to have large scale positive experience with hcq+azt when given to out patients, even to suspect symptomatic cases before results of the PCR tests came back.

        1. RA says:

          You don’t have to be a medical professional to have a useful comment! But, say some drug(s) makes those with mild COVID have slightly more mild COVID. That’s nice, but not really a game-changer that will allow us to go back to normal! We need treatments that actually reduce hospitalization, death, or severe extended debilitating outpatient disease (an outcome that is getting way too little attention, as an aside).

      3. Walther Grot says:

        A very small study was done at the “Resort at Texas City” : According to the Galveston County Daily News june 15 : 56 residents in this nursing home were infected with covid 19, 38 of them were treated according to Zelenko resulting in either 2 or 3 fatalities. The 18 untreated had 8 fatalities.

    3. Not a Doctor says:

      The article yesterday talked about using these drugs for prophylaxis, also turning out negative. Results that can’t be reproduced aren’t results, they’re anecdotes.

      I gladly welcome further research in this area, as the tools to identify patients early in disease progression will be very useful. In order to prove this hypothesis, finding the right patients will likely help improve the control group’s health over how the control group would have been without early treatment. I expect that this improvement will be more significant than any benefit from the drug.

      1. Paul says:

        The study did not use PCR for testing, which means that results are quite unreliable. An indian study testing the same prophylaxis hypothesis using PCR had results much more favorable for HCQ: http://www.ijmr.org.in/preprintarticle.asp?id=285520

    4. Athaic says:

      Neither Dr. Zelenko nor Dr. Raoult have ever advocated giving either HCQ alone, or HCQ+azithromycin, to hospitalized patients.

      Oh FFS, john , Raoult did advocate for his “game saver” protocol to be given under medical supervision. He certainly said so when we nasty known-nothing scientists started talking about side-effects and people self-medicating.
      Which means giving it in an hospital setting.
      One of the conclusions of his second paper was how taking his combo resulted in people being discharged earlier (earlier than what?, as there were no control group, but I digress).

      He also never emphasized the need to make it a combo. His conclusions from his first studies are very clear on this, while the addition of an antibiotic improved the results, HCQ alone was already showing effects.

      So at the very least start by defining “hospitalized patients”.
      If you mean “in ICU”, well, yes, duh.

  10. Philip says:

    No comment on this post, not even a typo spotting.

    I just wanted to give you a public thank you for the time and effort you have put in over the years and especially over the last few months. Finding nonpolitical information in this day in age is almost impossible, but very important.

    Again, thanks.

    1. Crocodile Chuck says:

      + 1, Derek

      1. David Young MD says:

        Yes, thanks Derek!!

    2. NICK says:

      – 1
      The whole idea of treating early keep the viral load low. HCQ and zinc with or without Azithromycine will not work once the viral load is already established. And once the viral load is established it lead to all the serious complications.
      When should the firefighters douse the flame , at the onset of fire or wait until the entire house in engulfed in flames.
      In real studies are designed to answer pertinent questions. Studies can be designed to show the out comes the researchers desire. Research is dead, long live bias.

  11. cynical1 says:

    Yeah, but clearly they got exposures way above the IC50 of HCQ in Vero cells. What could have possibly gone wrong?

  12. Alan Harper says:

    I really do hope that you will do a follow-up on Surgisphere, as I think that this story will tell us a lot about how big science and big data work, and if the worst aspects of the story are born out, how the conspire to give us the wrong answer.

    1. loupgarous says:

      As far as SurgiSphere, I’m still in suspension of judgment more – no reason (yet) to posit intentional malfeasance when stuipidity’s just as plausible as an explanation.

      That, however, doesn’t get SurgiSphere off the hook. Stupidity is legally actionable in handling of patient data under HIPAA and other laws for very good reasons – deciding you’re just going to blow off familiarizing yourself with those regulations isn’t an option when you solicit business from hospitals and clinics and sell your services to serious researchers.

      If SurgiSphere had actually succeeded in selling their “rapid COVID-19 assessment software”, FDA’s Forms 483 would be arrving at their offices in Chicago with enough force to embed themselves in the receptionist’s desktop. As it is, NIH’s research misconduct investigators ought to be very busy – if only as specialist consultants for the FBI to assess how much of this flap is intentional fraud, how much is covidiocy.

  13. Daren Austin says:

    Simple exposure response analysis of the Raoult study predicted that monotherapy was not antiviral. This larger study confirms that. The combination did have an effect on time to undetectable virus, but that isn’t outcome. Not surprised by this at all. But then it is not political here. https://link.springer.com/article/10.1007/s10928-020-09689-x

    1. David Young MD says:

      Well, tell that to the masses. If you at hundreds upon hundreds of individuals who comment on Youtube videos and online news articles about Remdesivir, vaccines, etc, etc, you will see over and over again about how Hydroxychloroquine is a wonder drug that is being deliberately ignored by the medical community. Every once in a while you will hear someone sneak in a comment about Zinc.

      Azithromycin? Give me a break. It is a macrolide antibiotic for bacteria. Do people really think that it has sufficient antiviral activity?

      1. john says:

        David,
        You might go to PubMed and put

        azithromycin viral infection

        into the search box, and educate yourself before making such categorical pronouncements.

      2. Daren Austin says:

        Not at all, but the combination of its anti-inflammatory effects with HCQ accumulation does predict a more rapid viral clearance (in swabbings not other sites) in patients presenting with U/LRTIs. Whether that is beneficial to outcome was not assessed. Don’t get me started on remdesivir – modest (at best) anti-viral with considerable nucleoside intracellular accumulation needed for activity

      3. NICK says:

        “Azithromycin, but not erythromycin or telithromycin, significantly increased rhinovirus 1B- and rhinovirus 16-induced interferons and interferon-stimulated gene mRNA expression and protein production. Furthermore, azithromycin significantly reduced rhinovirus replication and release. Rhinovirus induced IL-6 and IL-8 protein and mRNA expression were not significantly reduced by azithromycin pre-treatment.

        In conclusion, the results demonstrate that azithromycin has anti-rhinoviral activity in bronchial epithelial cells and, during rhinovirus infection, increases the production of interferon-stimulated genes.”
        https://erj.ersjournals.com/content/36/3/646.short

  14. loupgarous says:

    “therefor” (second paragraph, first sentence) works better with a final “e”.

  15. Marko says:

    Spain has discovered an intervention that reduces COVID-related deaths to near zero : Simply stop reporting deaths.

    It’s only a matter of time until this intervention becomes common practice throughout the world , and our COVID nightmare will be over , finally.

    Ain’t science grand ?

  16. loupgarous says:

    Thanks for sharing RECOVERY’s outcome re: HCQ with us. WHO’s SOLIDARITY study ought to be out pretty soon. Trump could put a lot of the “Sanofi stock” talk to rest by at least funding SOLIDARITY and other badly needed COVID-19 studies. At this point, it might be like arranging lounge chairs on the crew deck of the Exxon Valdez – the President’s dying the death of a Thousand Self-Inflicted (News)Paper Cuts.

    1. tollis says:

      IN THE recovery trial : doses of hydroxychloroquine given to patients
      2400mg HCQ during the first 24h
      (this is FOUR TIMES 600 mg recommended dosis)
      et 9600mg d’hydroxychloroquine for the whole session.

      according to drug guideline, a 1800 mg dosis in a day would require urgent hospitalisation .

      in other words, recovery test was designed to kill the patients.

      1. loupgarous says:

        The rationale for giving that high a loading dose has already been addressed by other posters – and it’s the reasoning WHO has been following, worldwide.

        So, it’s not just the RECOVERY study that loads doses this way to get optimal antiviral dosage. When the HCQ/CQ arm of SOLIDARITY study comes back with numbers, that’s likely to be the dosage administered to begin with.

        1. LRobin89 says:

          If WHO uses the same reasoning and dose, they are just doing the same mistake…
          Why not a non-toxic dose? Dose working in other hands? Like the doses from Raoult, Zelenko, India?
          Raoult et al showed that 600mg allows an efficient dose in lungs… No need to have a toxic high dose to get the virtual IC50…

  17. Lane Simonian says:

    Over-hyped treatments, discredited studies, promises of the development of vaccines at warp speed, and feeding frenzies over clinical trial results–it does not do much to inspire confidence in anything or anyone. Maybe the starting point should be a better understanding how this virus operates.

    When various clinical trial results are equivocal at best, it gets more and more difficult to try to squeeze out something positive. This of course does not just apply to hydroxycholoroquine either by itself or as a part of a combination therapy. In the absence of some earth-breaking study one way or another, it is probably time to move on.

    1. Tom A says:

      Thanks Lane. I was going to offer a similar comment, so +1. So many medical professionals are in a rush to try and prove they found “The $ilver Bullet”. A lot folks are caught up in a maelstrom at this point. It’ll be nice to revisit the science side of this pandemic in about 2025 give or take. I’ll just hope for something positive Real Soon Now.

  18. Simon Auclair the Great and Terrible says:

    Thank God and Greyhound HCQ is gone from here.

  19. David says:

    Good-quality clinical science is rarely easy, never quick, and often not easy for lay people to tell apart from quackery.

  20. Luciano Gasco says:

    It would be interesting to see the percentage of people infected with Covid-19 taking hydroxychloroquine for lupus and rheumatoid arthritis compared to the general population.

    1. Marko says:

      Stand by. Surgisphere has the data. Paper coming soon in either BJM or The Onion ( to be determined ).

  21. Ulrich Lingner says:

    From what I know about HCQ from other trials, I think the protocol in the Recovery Study is wrong. First, the dose is far too high. Such high dose used in a trial done in Manaus/Brazil, killed a lot of patients. Second, the HCQ belongs in the second randomisation, as an alternative for Tocilizumab to block immune response.

    1. Marko says:

      Look for similar fuckery in any trials involving Vit. D. Bolus loading doses of Vit D would likely upregulate clearance pathways , not to mention introducing unwanted side effects , negating any benefit. Slick trick , presumably well known by the big pharma hacks.

  22. Tony M says:

    Anyway, for those interested, The RECOVERY trial is a UK Trial, which will begin by testing some of these suggested treatments:
    Lopinavir-Ritonavir (commonly used to treat HIV)
    Low-dose Dexamethasone (a type of steroid, which is used in a range of conditions typically to reduce inflammation).
    Hydroxychloroquine – RECRUITMENT CLOSED
    Azithromycin (a commonly used antibiotic)
    Tocilizumab (an anti-inflammatory treatment given by injection)
    Convalescent plasma (collected from donors who have recovered from COVID-19 and contains antibodies against the SARS-CoV-2 virus).
    With 3132 patients already randomised to usual care alone we should be able to see some results soon on the alternative treatments been studied.

    This UK trial is distinct from the WHO’s “Solidarity” international clinical trial.The individual or combined drugs being studied in the Solidarity Trial are : are:
    Remdesivir
    Lopinavir/ritonavir combined
    Lopinavir/ritonavir combined with interferon-beta
    Hydroxychloroquine or chloroquine

    As of 3 June 2020, more than 3500 patients have been recruited in 35 countries, with over 400 hospitals actively recruiting patients.On 3 June 2020, the WHO announced it would resume its global trial of hydroxychloroquine after its data safety monitoring committee found there was no increased risk of death for treating severe COVID‑19 infection (presumably based on its data to date).

  23. Cherry Dator Soell says:

    Something I just read and want to share to keep everything in balance and fair
    http://covexit.com/oxford-recovery-evaluation-of-covid-19-therapy-flawed-against-hydroxychloroquine-and-dangerous-to-patients/

  24. Erik Dienemann says:

    Derek – thanks for your patience, perseverance and insights. Time to turn the page on this awful chapter in medical history. The Lancet study was a horrible scientific mess, in retrospect, but as I’ve said multiple times, it wasn’t really needed to conclude that HCQ was ineffective for hospitalized patients (given most observational studies showed no benefit, plus 60-80% of NY/US patients were being given HCQ in hospitals while the CFR doubled during the month of April) and this randomized, standard-of-care-controlled study should put an end to the arguing.

    We never ever should have been treating 60-80% of hospitalized COVID patients with a completely unproven treatment that wasn’t showing efficacy in most observational studies and it’s one more reason politicians shouldn’t be recommending medical treatments. Having said that, however, it would’ve been nice to have results from a more definitive trial like this 6 weeks ago – it’s also disappointing that we had to wait for a UK study for this info, when we have some of the best clinical research people in the world here in the US.

  25. tollis says:

    RECOVERY :
    they litterally KILLED the patient by using dosis of HCQ that are FOUR times more than the safe limit !
    so many people died in the name of fake science.

    1. Athaic says:

      Nonsense. HCQ is a very safe drug. Didn’t you listen to Pr Raoult and Dr Zelenko?

      1. Ulrich Lingner says:

        I don’t listen do Pr. Raoult anymore – he takes out of his studies and reports people that die or land in the ICU in the first three days. Is this science? Than, take a closer look on his first report – that about 42 patients. You will find out that what he tells is quite different from what the data show. About HCQ he has probably never said it’s safe. He said he used it to treat patients with intracellular bacteria, 200mg 3-times/day during up to 18 months, but he omits the number of treated patients – a handful or hundreds? This matters to conclude about safety. In former studies, regarding Lupus and Arthritis patients, 30mg/day/kg lean body mass was determided as lethal dose. Therefore, what tollis said is correct.

        1. Daren Austin says:

          The loading dose is based on the necessary accumulation needed to have a chance of achieving any useful pharmacological effect. For an acute disease there is little time for such accumulation. For chronic diseases like RA, it’s not a problem. Also the dose is not far from that for treatment of malaria. Don’t confuse this with the prophylactic dose.

          1. Ulrich Lingner says:

            Malaria: loading dose, 800mg followed by 400mg at 6 hours. Then only two more 400mg doses, at 24 and 48 hours of initial dose. Recovery trial: loading dose, 800mg followed by 800mg at 6hours and 400mg at 12 hours of initial dose; then twice 400mg for 9 more days, each 12 hours apart. Therefore, total loading dose for malaria, 1200mg, in the Recovery trial 2000mg. For me, the difference is significant.

  26. Robert Clark says:

    Wasn’t there another quite recent report where you said the door was closed on HCQ?

    I mentioned this before, but I have to say again I am dismayed that the experts in infectious disease do not say that these results with hospitalized patients under severe disease do not necessarily apply to early treatment cases.

    For instance there is no vaccine against HIV. But there are effective anti-virals which when *given early* can effectively prevent the progression of the disease. Obviously, these experts in infectious disease would want to get out to the public the effectiveness of these anti-virals for early treatment for HIV. And many of these experts promoted the research and development of these anti-virals against HIV. Would these experts have said give up on them if they didn’t work under severe HIV disease? Obviously, not.

    Yet that is the approach they are taking in regards to HCQ.

    Robert Clark

    1. Some idiot says:

      “ Wasn’t there another quite recent report where you said the door was closed on HCQ?”

      And with that pithy comment you imply that there is as much malfeasance/stupidity behind this report as there was behind the Lancet junk pile , without a shred of evidence to back it up… Great…

      You you compare the early times of developing treatments for HIV with those of COVID19, comparing HCQ with the early HIV antivirals. This would be a useful comparison if there was any solid data (ie RCTs) that showed useful efficacy of HCQ. But since there aren’t, it isn’t.

      1. Robert Clark says:

        Giving patients 2.4 gms per day, close to the lethal dosage of 3.0 gms per day, when the recommended dosage is 400 mg to 800 mg per day is astonishingly poor judgement.

        Robert Clark

        1. Some idiot says:

          See Daren Austin’s comment above.

  27. RA says:

    Hmmmm…why is Trump shipping our precious hydroxychloroquine to Brazil?

    https://www.whitehouse.gov/briefings-statements/joint-statement-united-states-america-federative-republic-brazil-regarding-health-cooperation/

    So, how does fact fit into the conspiracy? Because, as far as I can see, the “anti-HCQ conspiracy,” is being led by Donald Trump…he’s done nothing to get a legitimate early-stage trial of the Zelenko system studied, and now he is shipping our savior medication overseas!!! Hahaha!

    If I were a conspiracy theorist, I would wonder whether the whole Surgisphere debacle was sort of a James O’Keefe Project Veritas style set up to punk Lancet, NEJM, and WHO. That Surigsphere is a pro-Trump scam designed to keep the waters muddy…they knew they would get caught eventually or maybe even orchestrated getting “caught” so to fuel the conspiracies. But I am not a conspiracy theorist, so what do I know?!?!?

  28. Thomas Hager says:

    Derek — I hope you don’t close the door completely on doing new posts about HCQ, we need your well-informed viewpoint as the story continues to evolve. We are in the early stages of a very visible, highly charged examination of clinical trials in real time. We need as much calm, responsible scientific context as possible. Remember that all studies are partial, and no one study is definitive. People are emphasizing one or another that fits their viewpoint, critiquing and arguing, often from political or emotional bases. This all will result, eventually, I hope, in two things: A much better sense about what works to control Covid-19, and a new sense of humility in the research community. Debate is good, argument is vital, and all sides will eventually be heard. Until the dust settles, let’s all keep our powder dry and our minds open.

    1. Derek Lowe says:

      If there are significant new developments, I’ll come back to it. But if we just get more evidence that it doesn’t actually work, I won’t be covering that. Overall, I think that there are just better arenas than this one to go into clinical trial issues.

      1. JamesE says:

        Derek,

        I’ll add my thanks. I find this blog helpful. I think many are looking for an infallible oracle or prophet, which is silly. I also think keeping abreast of HCQ until its either vetted or dead is useful. There are not many places to go and find reasonable reporting on this stuff that is accessible. On a side note, it would be interesting to hear your thoughts on why covid seems to have hit some places, but not others. Is it purely pop density? Do some areas have high proportion of citizens on certain meds? Is it geographic? It seems covid’s impact is hardest in poor areas, which probably means places with more communal living.

        Either way, keep posting!

        1. Forye says:

          I second that. @derek it would be great to get your view on why say Slovenia did so well and Italy next door so badly. I have heard immunological dark matter mentioned and my eyes rolled.

        2. Rob says:

          Try Lagos, that`s well populated.

  29. Critical p says:

    What has happened to science? A glance at the death rates of countries who have used HCQ against the death rates of countries who have discouraged the use of HCQ seems to put the matter to bed! It would appear he who pays the piper calls the tune, these days it’s a right old racket. I look forward to the data once it’s out of the oven.

    1. Some idiot says:

      It would be nice if it was as simple as that, but there are so many confounding factors that this approach won’t really get that far… from general level of hygiene, to general level of healthcare, to observance of distancing; even to something as simple (but significant) as how they report deaths… I mean, up until (relatively) recently, the UK was only reporting deaths as COVID19-related if they occurred in a hospital (therefore excluding eg nursing homes).

      Yep. Let’s wait for the only solid data: the data from RCTs. Once enough of them have come in, we will finally be able to get a picture of what actually works… each RCT helping to fill in a hole in our knowledge of a part of the treatment “landscape.”

      1. Rob says:

        “occurred in a hospital (therefore excluding eg nursing homes”. No, they included both but not overall numbers, that has now stopped, just overall numbers now. Before April 13th UK provided recovery numbers obviously linked to the Hospital and nursing home death numbers, on April 14th no more recovery numbers were provided. Go to John Hopkins and post their link into the wayback machine to verify. The last time I calculated UK covid recovery`s in those institutions it was 3.8%, maybe that`s the reason the numbers are no longer available from John Hopkins, who by the way are funded by Bill Gates. You can try https://covid.bio though. https://www.youtube.com/watch?v=za1yRy_iY18 https://www.youtube.com/watch?v=9DNPnrHn_LA

  30. Glen L Weaver says:

    At this point, it is impossible to believe any reporting on the issue. I don’t think the journals involved should be considered top tier. Between this and Andrew Wakefield , The Lancet is just not believable.

    1. Some idiot says:

      Good point… To me, the most important thing is to get decent quality data on the table, and then have it looked at in public to see what conclusions stick. In the case of the Lancet car wreck, there was no data to see, so that was pretty “easy” (in the most unfortunate way, and at so many levels).

      To me, the way the data gets on the table is less important. In general, I approve of the concept of peer review, although much of the way it works at the moment sucks pretty badly. So, given the current situation, I feel it is just more important that the data is published ***somewhere***, so people can look at it and check it out. I don’t care where: a preprint server or just a normal website.

      Let’s get the data on the table, and see what it tells us…

      1. Edward R says:

        The data on HCQ shows that it has become increasingly unsafe since 2019.

        “From 1970 to Dec. 31, 2019, there were 24,728 adverse events reported to the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) for hydroxychloroquine, hydroxychloroquine sulfate and Plaquenil.

        Of those cases, 20,713 were serious, including 914 deaths. The FDA received nearly half of the reports (9,561) in 2019.”

        https://www.drugwatch.com/hydroxychloroquine/side-effects/

        1. Ulrich Lingner says:

          Interesting and at the same time disappointing. I do not trust these data, far too heigh. Some way to access the original FDA info?

          1. David says:

            FDA’s FAERS database is publicly accessible; just use Google to find “FAERS Public Dashboard”. While the data is widely available to the general public, the ability to interpret it properly is restricted to people with some experience in drug safety evaluation.

          2. This database is intrinsically hard to interpret.

            The numbers are much too high, because when a report comes in of an adverse event in a patient receiving 4 different drugs, then it is counted against each of them.

            On the other hand, the numbers are much too low, because there is not much incentive for caregivers to file reports. When I was at FDA, the accepted figure was that the database received reports on about 10% of fatal AEs, 1% of others.

            On yet another hand, the figures are biased, because newly-approved drugs, or drugs that are otherwise receiving attention, always get a flurry of new reports, only loosely related to the drugs’ frequency of use.

            I would pay attention to reports of weird AEs (thalidomide babies, angiosarcoma of the liver, sudden death in young healthy patients), but not much else.

  31. Robert Clark says:

    I would like to see what the “standard care” is for the controls. For some studies, the “standard care” included giving patients other antivirals, including some potent ones, such as interferon. “Standard care” wasn’t just, say, giving them extra oxygen and bed rest.

    I would also like to see what the actual numbers are for the RECOVERY trial. In another report on HCQ, the authors concluded it offered no benefit over “standard care”. (It’s one of those studies that called “standard care” being giving different antivirals.) However, when I looked at the actual numbers I was surprised to see the survival numbers for patients on ventilators were twice as good for those on HCQ(!)

    What happened was the overall numbers for the HCQ group and non-HCQ group were close, suggesting little benefit, so the authors reported only this fact in their conclusions. The fact the ventilators numbers were so much better for HCQ was completely overlooked.

    The report was:

    [Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19](https://www.nejm.org/doi/full/10.1056/NEJMoa2012410?query=featured_home)

    Here’s the graphic from the Supplementary pdf file showing ventilated patients on HCQ actually had twice as good survival numbers as those not on HCQ:

    https://pbs.twimg.com/media/EX3y0M9WoAM6EPL.jpg

    Robert Clark

  32. Ulrich Lingner says:

    Interesting and at the same time disappointing. I do not trust these data, far too heigh. Some way to access the original FDA info?

    1. Robert Clark says:

      Ulrich, are you referring to the study I posted? Some of the original, unadjusted numbers are giving in tables in that report. Others are given in a supplementary appendix:

      https://www.nejm.org/doi/suppl/10.1056/NEJMoa2012410/suppl_file/nejmoa2012410_appendix.pdf

      Robert Clark

      1. Ulrich Lingner says:

        Sorry, I posted my comment at the wrong place. Thanks for your reply.

  33. Popper says:

    Here an independent experience of cure using the combination Azi plus Hydro

    https://la1ere.francetvinfo.fr/guadeloupe/hydroxychloroquine-10-patients-traites-au-chu-guadeloupe-ont-eu-effets-secondaires-839818.html

    … the scientific comunity have to search some benefit on the viral shedding giving the associtation at the first fases of the covid syndrome ASAP. If you do other than this you will test another phenomena not the cure developed by Margliese doctors…this is simply to understand.

  34. Fayerabend says:

    Here an interesting experience using the combination Azi+Hydro

    https://la1ere.francetvinfo.fr/guadeloupe/hydroxychloroquine-10-patients-traites-au-chu-guadeloupe-ont-eu-effets-secondaires-839818.html

    If you did other than test the combination at the first fases of the covid syndrome you will test another phenomena not the cure developed in Marsiglia…this is simply to understand.

  35. steve says:

    IF THE STUFF ACTUALLY WORKED CLINICALLY WE’D KNOW BY NOW. PERIOD. ENOUGH EXCUSES AND AD HOC ADD ONS TO THE HYPOTHESIS, IT’S DEAD. LET’S MOVE ON.

    1. Alan Goldhammer says:

      An Data Safety Monitoring Board overseeing a HCQ trial would stop it if there were convincing positive or negative data. That this has not happened ought to tell everyone that it is not the wonder drug.

    2. Robert Clark says:

      Doctors who have tried it for *early use* found it works for early use. Doctors who have never tried it for early use claim it doesn’t work for early use.

      Robert Clark

      1. Some idiot says:

        Again, no RCT there, so it remains speculation. Interesting speculation, but speculation regardless.

        1. Robert Clark says:

          It’s a question of logic. Is it to be believed the doctors, of which there are many, who say they’ve tried it for early use and found it works for early use. Or the doctors who have never tried it for early use and then claim it doesn’t work for early use?

          Coronavirus: How Turkey took control of Covid-19 emergency.
          By Orla Guerin
          BBC International Correspondent, Istanbul
          29 May 2020
          Turkey embraces hydroxychloroquine.
          “Chief doctor Nurettin Yiyit – whose art work is on the hospital walls – says it’s key to use hydroxychloroquine early. “Other countries are using this drug too late,” he says, “especially the United States. We only use it at the beginning. We have no hesitation about this drug. We believe it’s effective because we get the results.”
          https://www.bbc.com/news/world-europe-52831017

          CORONAVIRUS
          The Battle Over the Numbers: Turkey’s Low Case Fatality Rate.
          BLOG – 4 MAY 2020
          “Despite the prevalence of the virus among the population and rapidly increasing infection rates, what is striking is Turkey’s lower death rate. Turkey’s death rate per 1 million population is 37, making it even more successful than most comparable European countries for COVID-19. On the basis of official figures, Turkey ranked better than Germany, which has received a great deal of attention and admiration for its low fatality rates.”
          COVID-19 Rates (as of 30 April 2020)
          Country Total cases Total Deaths Deaths/1 M pop. Tests/1 Million pop.

          USA 1,064,572 61,669 186 18,549
          Spain 236,899 24,275 519 30,253
          Italy 203,591 27,682 458 31,603
          France 166,420 24,087 369 7,103
          Germany 161,539 6,467 77 30,400
          UK 165,221 26,097 384 12,058
          Turkey 117,589 3,081 37 11,157
          Source: Worldometer Germany
          https://www.institutmontaigne.org/en/blog/battle-over-numbers-turkeys-low-case-fatality-rate

          Robert Clark

        2. theasdgamer says:

          Got any evidence that RCTs have ever helped with novel acute infectious viral diseases? SARS, MERS, H1N1, ebola

          1. Some idiot says:

            Ok… The vaccine created for ebola was (after phase 1 results indicated that antibodies were produced on administration) granted permission to not run RCT since it would be ethically wrong to do so with an infection that has such a high death rate (which is certainly not the case for COVID19).

            On the other hand, there have been many, many RCTs for antivirals for influenza-type infections (Tamiflu springs quickly to mind; there are others as well). They have clearly demonstrated the usefulness of these treatments (modest in some cases, useful in others). In addition, they have shown what sort of a treatment regime is required, backed up with _data_.

          2. theasdgamer says:

            So no RCTs have been useful for NOVEL acute viral infections. Thanks for the confirmation.

          3. Some idiot says:

            False. Antivirals were run in RCTs against H1N1 (plus I think MERS, and maybe SARS). You have the wrong page. This is a scientific page, called “In the Pipeline.” You would appear to have been looking for “Trolling for beginners.” Take your misinformation and lack of scientific understanding elsewhere.

          4. theasdgamer says:

            Oh, I see the problem. You need to go to the logic section where you learn to answer the question asked instead of diverting and distracting. I’m still waiting for instances where RCTs delivered results in time to be of benefit for treating NOVEL acute infectious viral diseases. Didn’t happen with SARS or MERS. We don’t need your faux science here.

        3. NICK says:

          Tamiflu has the same issue as HCQ , if you do not use early it will not work.

  36. Jack Morris says:

    Like cancer, it is better to fight COVID during the earliest stage of detection. Many studies are late stage when the virus (like stage 4 cancer) has done irreparable damage to the body. Here is a doctor from Yale who believes that HCQ + macrolide (aka antibiotic) as well as HCQ + macrolide + Zinc is effective if used early on after diagnosis.

    Yale School Medicine Dr. Risch: Using HCQ and Other Drugs to Fight Pandemic
    https://publichealth.yale.edu/news-article/25085/

    Note that above link is a summary of Dr. Risch’s take on efficacy of HCQ. That article contains a link to a PDF file that provides a full description of Risch’s reasoning.

    1. Some idiot says:

      Yes, the theoretical possibility exists (nothing new there). But the fact remains that no RCTs have shown efficacy, so therefore there is no solid data to show that it works. Still.

      1. theasdgamer says:

        No, there is solid evidence that HC / zinc works–it’s called overwhelming anecdotal evidence… the same sort of evidence for our claim that water is wet.

  37. Lapalisse says:

    Dear Some idiot do you know how there is not at all a RTC with the aim to test the Marseille cure? If it worked the people saved their life…but at the moment all the RTCs are testing last stages od the Covid Syndrome with a bordeline toxic dose of Hydro (without Azi) or strange hypoteses of post-prophilaxes of people that were in contact for almost 10 minutes with positive people using a symptomes checklists…:-) are those useful randomized trials during a global pandemic? Let me know

    1. Some idiot says:

      I understand that RCTs are registered after approval to start with. One thing is certain: no RCT showing efficacy has been made public. Therefore there is no solid data to say it “works.”
      Concerning the “borderline toxic dose” as you describe it: that has been explained by others in previous comments.
      I am sure that the results of more RCTs will be published in the future, using other combinations (I look forward to seeing them). But as yet, there are no RCTs which show efficacy.

  38. Robert Clark says:

    I want to say OMG again but that doesn’t begin to cover it. Is it really true that the lead doctor of the RECOVERY trial mistook hydroxychloroquine for hydroxyquinoline, a drug used to treat amoebic dysentery, and that is why they prescribed toxic dosages of HCQ?

    From an interview with France Soir:

    EXCLUSIVE INTERVIEW: Martin Landray, Recovery – end-of-game hydroxychloroquine in the UK.
    Posted on 06/06/2020 at 8:30 p.m. – Updated at 11:06 p.m.
    “FS: Could you please specify the HCQ dosage that you gave to the patients?
    ML: It is 2400 mg in the first 24 hours and 800 mg from day 2 to day 10. It is a treatment over 10 days in total. These are doses high enough to ensure that the level of HCQ in the blood is high enough to have a chance of killing the virus .

    FS: How did you decide on the HCQ dosage?
    ML: The doses were chosen on the basis of pharmacokinetic modeling and these are in line with the dosages used for other diseases such as amoebic dysentery .

    FS: Is there a maximum dosage for hydroxychloroquine in the UK?
    ML: I have to check, but it’s much more important than 2400mg, I think it’s six or ten times more.
    For Covid, there is no recommended dose because it is a new disease and because hydroxychloroquine is not a drug authorized for use in Covid positive patients.”
    http://www.francesoir.fr/politique-monde/interview-exclusive-martin-landray-recovery-lhydroxychloroquine-fin-de-partie-au-uk

    He is literally saying the maximum dosage of HCQ is 14 to 24 gms, which is an absurdity. What is it about HCQ and COVID-19 that lead very accomplished and experienced researchers to make unfathomable mistakes?

    Robert Clark

    1. Some idiot says:

      Are you honestly trying to claim that a lower dose would have given a better result? If so, why??? What _data_ do you have to suggest this?

      If not, this is irrelevant. Data talks.

      1. theasdgamer says:

        Clearly, if you give 100,000 units of heparin you should obtain better results than merely giving 5,000 units.

    1. Some idiot says:

      Ok, I will ask you the same question… Would you have expected better results with a lower dosage? And if so, why??? Data, please.

      1. Robert Clark says:

        Any prescription medication in sufficient overdose levels can be toxic or even lethal. Opioids for example are used in pain management but can be lethal in overdose. Even over-the-counter medicine such as aspirin can be lethal at sufficiently high overdose levels.

        For the RECOVERY study, it was given to patients under severe disease at high dosage levels. COVID-19 damages the heart, as well as other organs. Under overdose levels HCQ’s heart effects become worse, which would thus worsen COVID-19 patients already damaged heart condition.

        In addition to its antiviral effects, HCQ is known to be an immunomodulator or immunosuppressant. This means it can limit the bodies immune response. This is probably why it is effective for lupus and rheumatoid arthritis because they are autoimmune disorders.

        For COVID-19 one of the most dangerous effects is the over response of the body to the presence of the virus, known as the cytokine storm. If HCQ can suppress this over reaction of the immune system, it could be an effective medication even in later stage disease.

        BUT, because it can suppress the body’s immune response, it can also allow the progress of secondary infections when given in too high amounts.

        About the toxic dosage given to patients in the RECOVERY study and the implication by the study lead that maximum dosage of HCQ is in the range of 14 gm to 24 gm, here’s a case study showing it is well below that:

        American Journal of Respiratory and Critical Care Medicine 2010;181:A6080
        Acute Hydroxychloroquine Overdose: Case Report, Literature Review, And Management Recommendations.
        Rebecca J. Kruisselbrink , S Zaki Ahmed ,
        “A 23-yr old female presented to the nursing station on a northern reserve sixty minutes after ingesting 8 grams of hydroxychloroquine.”
        https://doi.org/10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A6080

        Robert Clark

        1. psoun says:

          I really don’t get these massive dosages of HCQ in many of these trials, particularly for severe patients. As HCQ seems to work fairly slowly, it would not seem that appropriate ex-ante for severe cases, even with such a boosted loading dose, and most definitely not for those with contraindications (heart disease, elderly, etc.) who are over-represented in severe Covid cases.

          It does seem likely the IL-6 effect is overwhelmed by other factors, though the noise of dosage makes that hard to pick out.

          I’m waiting to see what Boulware’s next two RCTs show as those will (hopefully) be more conclusive. However, this below is interesting on the use of folic acid as a placebo in the first one. Interesting that severity scores for HCQ and placebo (folate) in Boulware’s first RCT were pretty similar (and pretty low, in the high 2 range on a 10-point scale IIRC) for cases that came down with Covid.
          https://twitter.com/TWenseleers/status/1269157078544855041

        2. Some idiot says:

          The problem with your hypothesis is that there is no indication from the data from this trial that the high doses gave problems with toxicity. Instead, as has been carefully explained by others, the high initial doses were to get the pharmacokinetics working as quickly as possible…
          And the other studies you mentioned… Not RCTs, I presume? Otherwise we would have probably heard of them before.

          1. Robert Clark says:

            You can also get high initial blood levels by giving an overdose; that doesn’t mean it is a good thing.

            You are correct the other studies showing beneficial effects at lower dosage aren’t definitive. But consider this: IF they are correct, than giving these high dosages were counter-productive. They prevented the beneficial effects that would have occurred at lower dosages.

            Robert Clark

          2. Rob says:

            Didn`t they do that with Aspirin in 1918, didn`t work did it.

          3. Rob says:

            Didn`t they do that with Aspirin in 1918.

      2. WST says:

        Prof Didier Raoult comments the Recovery study on Tweeter:

        “Didier raoult @raoult_didier·2h
        The Recovery test clearly shows one thing: with an initial dose four times higher than that we use in Marseille, higher than the maximum authorized in the recommendation books (see Vidal), hydroxychloroquine is not toxic to patients.

  39. critical p says:

    Hey Some idiot. The difference in death rates, between counties using and not using HCQ, is by two orders of magnitude! you cant just brush over that level of discrepancy. Are you suggesting western society don’t know to wash their hands and Asians cant count once they’ve run out of fingers and toes, give me a break. Next you’ll be telling me that 40 years of a grand solar maximum wouldn’t cause moderate warming of the planet. And huge steel structures can just tear them selves apart. These days there are lies, damn lies and global corporate narrative, sadly.

    1. Some idiot says:

      There is one thing that is certain, and that is that you do not understand nuances in an argument…

  40. Lapalisse says:

    Some idiot

    there are two phases of the covid syndrome first cold like symptomes and the Raoult data show us that low doses of Hydr + low doses of Azi blocked the viral shedding (at the moment nobody have tested this with rcts but you had observational study).

    https://pubmed.ncbi.nlm.nih.gov/32387409/?from_term=didier+raoult&from_sort=date&from_pos=8

    in the second phase (the pneumonia) probably it is important test a multitherapy and probably are more important immunomodulators and anticoagulant

    here the data (but there are a lot of clinical/observational studies)

    https://www.medrxiv.org/content/10.1101/2020.05.29.20117358v1
    https://www.medrxiv.org/content/10.1101/2020.05.30.20117929v1

    also in this second phase there is an interesting study about Hydro-Azi-Zinc (low doses than the recovery trial)

    https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1

    so the clinical and observational studies show us that there are more that one stage in the covid syndrome and that probably a multitherapy is more efficient that a monotherapy.

    plan a good rtc is not simple and before is fundamental a good model to test, randomization is not the entire story, so important is the fact that the researcher had their ideas clear (Ch. S. Pierce, How to Make Our Ideas Clear, 1878).

    Moreover it is important that the rtcs test the clinical and “anatomopathological” hypotheses….history of medicine and history of science are very important to do good research. Anatomopathology is very important to plan therapy…by making autopsies they noticed for example that covid pneumonia is characterized by blood clotting …. how can you cure this clinical picture with high doses of hydroxychloroquine? Hydroxychloroquine and azithromycin and perhaps zinc is useful for blocking the syndrome at the beginning (and probably saving lives and blocking the viral spread in the population … this is what the observational data tell us so far).

  41. Lionel Maitrepierre says:

    What about
    1. The fact that the trial is based on 4 times the recommended prescription (500mg a day usually) at a level that is considered to be an overdose which requests hospitalisation on its own…
    2. What about the fact that Landray says that the products tested is used to treat diarrhea, whereas HCQ has never been indicated for this? Any confusion with hydroxyquinoline as Dr. Perrone suggests?

    Is there a #RecoryGate behind again?

    http://www.francesoir.fr/societe-sante/recovery-brexit-overdose

  42. Robert Clark says:

    Here is study that HCQ can be effective under a severe disease condition using low dosages comparable to those commonly taken by lupus patients:

    Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19.
    Bo Yu1, Chenze Li1, Peng Chen1, Ning Zhou1, Luyun Wang1, Jia Li2, Hualiang Jiang2,3 & Dao-Wen Wang1*
    Received April 23, 2020; accepted May 12, 2020; published online May 15, 2020
    “Additionally, lower plasma levels of IL-6 after HCQ treatment are highly correlated with the application period of HCQ. IL-6 levels returned quickly to the levels of NHCQ patients after HCQ treatment was stopped. This finding in- dicates that we need to adjust our treatment regimen by extending the use of HCQ until patients are completely cured.
    We also noticed a couple of negative reports about CQ and HCQ (Geleris et al., 2020; Mahevas et al., 2020; Magagnoli et al., 2020). However, based on the results in these studies, it is very likely that they used high doses of HCQ, which might induce cardiotoxicity and death. They might also have used high doses of HCQ as antiviral agents rather than for anti- inflammation. In contrast, the dose of HCQ used in the present study is much lower than that in previous studies but is the same as used for treating inflammatory diseases, and thus HCQ for COVID-19 patients works more likely as an agent for anti-inflammation and immunomodulation, rather than as a direct antiviral agent.”
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228868/pdf/11427_2020_Article_1732.pdf

    Robert Clark

  43. critical p says:

    That’s right Some idiot if you can’t win the argument just insult the other person and run away. You need to come up with a credible explanation for the disparity in death rates to win this debate my friend. What about you Derek, any ideas?

  44. Marko says:

    Balloux ” “I’m not claiming biomedical research is perfect. Though, those who claim that the rapid retraction of the Lancet and NEJM Surgisphere papers are proof of dysfunctionality and corruption are missing the point. If anything, it demonstrates that the system is refreshingly healthy.”

    https://twitter.com/BallouxFrancois/status/1270091287199395840

    Hehe. Seems like he’s laying the groundwork for a retraction of his own designed-to-fail HCQ prophylaxis study.

    Refreshingly healthy , my ass. Disgustingly rotten is more like it.

  45. critical p says:

    Ok Some idiot maybe i’ve been a little flippant but are you seriously suggesting that the ineptitude and outright dishonesty of nearly all the governments of the world is the reason for the radically different death rates? Is it possible that the countries (Africa,Asia) who allow the use of HCQ just happen to be the counties which substantually under report covid 19 deaths, and the countries(Europe,North America) who discourage the use of HCQ just happen to be the countries which have failed to provide the resources required to deal with this virus or/and are claiming people have died of covid 19 when they have really of something else? Is that what you are saying? do i need to go into more nuance?

  46. RA says:

    I find it interesting that a lot of people think you can just compare 2 countries’ death rates and attribute the difference to use or non-use of hydroxychloroquine. There are a lot of factors that can explain the differences between countries:

    https://www.medpagetoday.com/infectiousdisease/covid19/86527

    But, assuming such factors will be unconvincing to those who believe that a country’s support for hydroxychloroquine is determinative, I am curious how they explain Brazil? Led by Jai “Tropical Trump” Bolsonaro who is pushing hydroxychloroquine hard, Brazil is not doing well at all. In fact, things are not going well in the “Axis of Hydroxychloroquine” the 3 countries led by far-right hydroxychloroquine lovers…Brazil, India, and the US.

    1. critical p says:

      Well RA first HCQ has been easily accessible in a majority of countries not just 3! Just like Trump, Bolsanaro had to fight national institutions who worked very hard, and continue to, to prevent HCQ being available to their respective populations, remember the murderous trail in Brazil where they gave recruits lethal doses of chloroquine in an attempt to discredit the treatment, pretty desperate stuff i think you’ll agree. Indeed many doctors in US still refuse to prescribe HCQ to covid 19 patients because of FDA guidance. In India social distancing simply wasn’t possible in shantitowns so many such populations were provided with HCQ on mass this seems to have been successful as they have a death rate of only 5 deaths per million at present. In subsaharan Africa most people were already taking HCQ to combat malaria which I suggest is the reason for the very low incidence of covid 19 there. The fact is every study which claims to find HCQ is not an effective treatment for covid 19 has been proved to be deceptive as, i’m sure, this Oxford study will be also, why? I would suggest there just isn’t any money to be made from HCQ. So RA to coin a phrase from the climate change fraud, is the science settled?

      1. RA says:

        Ohhhh…I see! So, when a right wing hydroxychloroquine promoting leader has high death rates it’s because of entrenched oppostion to HCQ…and when countries have low death rates, it is automatically from HCQ and has nothing to do with variations in testing, lockdowns, border closures, luck, demographics, underlying chronic conditions, etc.

        Hahaha…why haven’t “strongmen” Trump and Bolonaro gotten a decent early stage study of HCQ by now? Are they so weak that they can’t even get a decent study done by now?

        Perhaps they are waiting for the outbreak to be over so they can then trot out data “vindicating” them at a time point when it’s too late for the med to do anything..in trump’s case, I wonder if he is planning for a fabricated pro-HCQ study to come out in October right before the election….maybe it will be a Brazillian study.

        You attribute the lack of interest in early-stage HCQ to the fact that there is no money to made in it. So why aren’t you and your ilk as vociferous promoting quercitin, famotidine, ivermectin, or a whole bunch of other potential cheap treatments that need more study? Are you only interested in the cheap treatments promoted by Trump? I wonder about the motivations of the militant pro-HCQ folks…is it political and/or are they affiliated with hedge funds shorting Gilead? Remdesivir isn’t impressive either, for what it is worth.

        1. critical p says:

          Ok RA yes US and Brazilian, (i see you’ve dropped India from your right wing evil list), death rates are higher than they would have been had their respective health institutions embraced the use of HCQ(like India did). Politicians, quite rightly, are not responsible for the design of drug trials. The big money to be made from this pandemic is of cause vaccine development and role out. Big pharma have huge influence in all national health institutions in Europe and US and other countries such as Brazil which is the reason for the ridiculous study designs regarding chloroquine and HCQ we have seen. Chinese doctors tried out most of the drugs you mention but determined HCQ to be the most effective and published dosing and duration advice on feb 19th. Remdesivir is also pretty good but is expensive, has limited supply and needs to be administered intravenously so is not suitable for outpatients. I must say for someone who asks a lot of questions you don’t seem very well informed.

          1. Edward R says:

            Keep an eye on Brazil’s deaths to recoveries ratio on Worldometer. They have been getting better lately since Bolsonaro fired his Minister of Health who had opposed HCQ use like Fauci.

            Just another coincidence or political interference? Maybe, but then again maybe not.

          2. loupgarous says:

            “Keep an eye on Brazil’s deaths to recoveries ratio on Worldometer. They have been getting better lately since Bolsonaro fired his Minister of Health who had opposed HCQ use like Fauci.”

            That didn’t age well. Brazil’s right behind us in “number of confirmed cases” despite a full-on effort to use CQ early intervention in COVID cases (HCQ is a no-go there becaise of a patent rights dispute.

          3. Edward R says:

            Bolsonaro legislated HCQ use on May 20th when the death to recovery rate was 14%. If you check today it’s down to 9%.

            https://www.aljazeera.com/news/2020/05/brazil-coronavirus-deaths-reach-daily-record-crisis-deepens-200520000716007.html

            Not saying Bolsonaro knows anything about the effectiveness of HCQ but he hit the nail on the head when he criticized the New England Urinal of Medicine studies lol!

          4. Edward R says:

            @loupgarous

            https://medicalxpress.com/news/2020-05-brazil-chloroquine-mild-covid-cases.html

            That’s an EARLY treatment protocol he was recommending. As far as I know they never used that before. Their HC trial was another overdose sham like the NIH seems to prefer.

            In the land of the free turns out everyone isn’t so free after all.

            Brazil…

            “The guidelines, which apply to the public health system, leave the final decision on using the drugs up to doctors and their patients.”

            USA… (not-so-much)

            https://www.cnbc.com/2020/06/15/fda-revokes-emergency-use-of-hydroxychloroquine.html

  47. Omar Stradella says:

    This paper (https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa191/5849074) explains the rationale for a loading dose of HCQ in the COVID-19 trials:

    “In the case of hydroxychloroquine, the desired target concentration might be the EC50 against SARS-CoV-2 (242 ng/mL) and we used the volume of distribution (5522 L) for a calculated loading dose of approximately 1336 mg at Day 1.”

    Also the problem is that HCQ has a very slow onset of action:
    “Based on pharmacokinetic predictions in healthy volunteers, a period of 6 months on oral hydroxychloroquine sulphate 200 mg tablets once daily is required to achieve 96% steady-state concentrations of hydroxychloroquine”

    In the end the authors chose a lower loading dose based on adverse events concerns raised in another paper (https://pubmed.ncbi.nlm.nih.gov/10025931/) that used 1200 mg/day for 6 weeks for RA. Although, they were mostly GI adverse events and patients were receiving naproxen too (which certainly contributed). They concluded that “HCQ dosages of up to 1,200 mg/day for 6 weeks are well-tolerated, except for effects on the GI tract.”

  48. Actually this research that you talk about proved to be not reliable
    as you think and they got it removed from science sites. They mocked Trump for using it around the clock and WHO decided to stop experiments just based on that research and guess what? It was a fake news

  49. Mark says:

    Your exasperation is palpable- I’d be exasperated too. Keep fighting the good fight, for science and for truth!

  50. Robert Clark says:

    https://www.sciencenews.dk/en/suspect-research-may-be-the-end-for-a-potential-covid-19-drug
    “The Danish researcher behind an ongoing trial of hydroxychloroquine regrets that the excessively high doses of these drugs administered in the published observational studies threaten other potentially promising attempts to save lives” #research #science
    https://twitter.com/novonordiskfond/status/1270442710919450625?s=21

    Robert Clark

    1. Edward R says:

      What confounds me is that these same researchers who are conducting early treatment are also sitting on useful data that they never divulge.

      If treatment starts with the onset of breathing difficulties the results are reportedly nearly immediate. Unlaboured breathing is restored in 8-12 HOURS. Fevers are broken within 24 HOURS. Viral load is undectable in 6 DAYS.

      If you claimed to develop a paint that completely dried in 8 hours how long would it take you to test that claim?

      One day?

      One week?

      With HCQ it’s always a 6 month long task.. WTF?!!!

      That said… and confounding variables aside… the countries that use an early HCQ protocol UNIFORMLY have extremely low fatality rates. Either they are complicit in a massive conspiracy for unknown reasons or the rot (ineptitude and corruption) in the medical research community runs deeper than we think.

      Let’s all hope against hope that early HCQ does NOT work. If it does the public trust in medical science and our already transparently corrupt politicians will be shattered. I also strongly suspect social unrest will not be getting any better.

      1. Marko says:

        “Let’s all hope against hope that early HCQ does NOT work. If it does the public trust in medical science and our already transparently corrupt politicians will be shattered. I also strongly suspect social unrest will not be getting any better.”

        Yes , we must keep the grift going. Wouldn’t want the broader public to finally awaken to the reality and angrily demand change , would we ?

      2. Marko says:

        “What confounds me is that these same researchers who are conducting early treatment are also sitting on useful data that they never divulge.”

        Plenty of such useful data HAS been released , and then quickly dismissed because it wasn’t part of a RCT.

        RCT data can’t be released quickly , because they’re extremely time-consuming to get up and running , not to mention the effect of fraudulent propaganda like the Surgisphere and Boulware studies , which severely impact ongoing recruitment efforts. We may never see the data from those trials as result , which is the goal , I believe.

      3. David Young MD says:

        Edward R.

        You have to clarify what you are saying and give references to prove your point. That’s a bold statement to make without being able to back it up. And what do you mean by “extremely low fatality rate?” I mean, does that mean that just 0.5 percent of people die? In the US, it appears that there is about a 5 percent death rate from Covid19. 100,000 deaths out of almost 2 million reported cases (realizing that there may be a lot of other unreported cases).

        In Brazil 38,701 deaths out of 747,561 cases, which is about 5 percent (I thought they used a lot of Chloroquine there)

        In Italy 34,114 deaths out of 235,000 cases, which is over 10 percent.

        In Russia, 6,358 deaths out of 493,000, which is just over 1 percent, but I don’t trust the Russian data (do you) and I don’t recall that they used Hydroxychloroquine.

        Now Saudi Arabia is under 1 percent… but, I don’t think that I trust their data either.

        Do you have more authoritative information that proves your point.

        1. Ulrich Lingner says:

          Cases numbers are meaningless to determine fatality rate. They depend on how much is tested. A Survey in Brazil, finished May 21, found that 1.4% of population was already infected. There, asymptomatic or people with wild symptoms isn’t tested and therefore don’t add to cases. Using the deaths at this date, the fatality rate was about 1.2%. Similar numbers were found in a recent survey in Spain – fatality rate about 1.2% with 5% already infected.

        2. Edward R says:

          Actually Dave I think I made my point quite clearly. I am amazed you can’t follow it.

          Let’s try this…

          Give the HCQ treatment EARLY like say Bahrain does. 16,200 confirmed cases, 11,109 recoveries and only 32 total deaths reported today.

          Next give it only to symptomatic cases experiencing breathing difficulties, those over 60 and those who have comorbidity factors like Zelenko does. Might as well add the zinc to the HQC and Az to make everyone happy.

          Then you just test viral load until it goes to zero or the patient dies. Then you simply count the days if they can do that. Then just present that raw data. This way nothing is subjective like alleviation of symptoms or release from hospital. Also try not to overdose them with those crazy high amounts we keep seeing. Use the 800mg first day and 400mg the following days like Zelenko.

          Do you think they are capable of doing that?

          If it works then great. If it does not work then great as well. At least we have an answer. At this point I really don’t care if it works or not. Honestly I hope it DOESN’T but at least we find out now because if it does it has the promise to save lives like Yale Professor of Epidemiology Harvey Reisch says it does.

          If you have any further issues with what I am saying I suggest you take it up with Harvey. He has a PhD behind his name if you didn’t bother to check his paper out.

        3. Robert Clark says:

          Dave, here is collection of links for countries having low COVID-19 death rates correlated to early HCQ use:

          Clues to hydroxychloroquine effectiveness in cross-country comparisons. UPDATED: 6/10/2020.
          http://exoscientist.blogspot.com/2020/06/clues-to-hydroxychloroquine.html

          However, correlation is not causation. A problem is that there are several confounding factors. For example, in the Asian countries they also have much lower levels of obesity which may be a contributing factor to their much lower death rates.

          In the update, I also included within-country comparisons for Italy and France as this is more definitive.

          Robert Clark

  51. Ippocrate says:

    Here other infos about the fact that give just high doses of hydro to terminal patients is completely irrational and ineffective….the last stage of covid syndrome involves, in a very hard way, cardiocirculatory and immunological systems.

    https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30434-5/fulltext?dgcid=hubspot_email_newsletter_tlcoronavirus20&utm_campaign=tlcoronavirus20&utm_medium=email&_hsmi=89194345&_hsenc=p2ANqtz–RmGDEA6R_vZk0-VI2ilm-GTTx4ZeB4HfcN3GipjaA3Noue-6

  52. Robert Clark says:

    Discussion of differences in COVID-19 death rates correlated to prevalence of HCQ by country:

    Clues to hydroxychloroquine effectiveness in cross-country comparisons. UPDATED: 6/10/2020.
    https://exoscientist.blogspot.com/2020/06/clues-to-hydroxychloroquine.html

    However, because of so many confounding factors such as different levels of obesity in differing countries, I updated it to look at two countries Italy and France that also show such disparities between provinces in the same country.

    Robert Clark

    1. Edward R says:

      Great job Robert. This is what I am talking about.

      The confounding variables are certainly there for some places with low mortality rates that use HCQ like the Middle East where the population is younger as are the foreign workers who reside there. Often those same countries have very high testing rates as well so they are more than likely to pick up many asymptomatic cases possibly driving the mortality rate down. In many other countries we can probably count on the under-reporting of deaths because of political considerations. Still there are simply WAY too many of these HCQ countries reporting low mortality rates and sometimes those rates in inconsistent use countries are extremely regional like in France.

      All we want is an answer. And we want it NOW.

  53. ppjm says:

    What is the state of the story with Covid-19 and nicotine?

    A couple of months ago, there were some papers suggesting smokers were less likely to suffer serious effects from SARS-CoV-2 infection, with various mechanisms proposed concerning nicotine. Now there seems to be a spate of papers saying that smoking increases the risks, rather than decreasing them. Is this it?

    1. Tom says:

      I have no idea regarding any potential interaction between Covid-19 and nicotine. What I will say is that common sense would clearly suggest that smokers are much more likely to be at a greater risk given what smoking does to the lungs with regards (tarring etc.)… given the disease affects the respiratory system I don’t imagine many health professionals will advocate smoking as a way of decreasing risk!

    2. critical p says:

      Smokers are used to reduced oxygen concentration therefore may have less sensitivity to the action of the virus. just my theory.

    3. JL In Jersey says:

      This is interesting, my grandfather was a NYC policeman during the 1918 Spanish Flu. Things got very dire and if you came down with the flu they came and took you away to a field hospital. This was done to protect the remaining family and help contain the pandemic. My mother was a three year old at the time, home with a baby sister. To protect the family the doctor assigned my grandfather recommended that my grandfather chew tobacco all day, and in the evening spit it out and gargle with Scotch. He was also instructed to wash up and change outside the home. No one in the family became ill.

  54. Tom says:

    Just to add, if you go by that logic you may as well believe the President’s ridiculous advice regarding ingesting bleach (DO NOT DO THAT).

    1. Edward R says:

      He never recommended ingesting bleach. He recommended injecting it instead. Big difference. Works faster doing whatever he thinks it’s supposed to do I guess.

      https://www.vox.com/platform/amp/2020/4/24/21234427/trump-coronavirus-bleach-injection-ultraviolet-light-treatment

      All I can say is that if HCQ works you had better get used to another 4 years of that unless Gilead quickly comes up with a dementia cure for Biden and his son Hunter’s dealings with Burisma and China never see the light of day.

  55. Ippocrate says:

    on the low doses of hidroxy

    https://pubmed.ncbi.nlm.nih.gov/32418114/

    the problem is to find a multi-therapy not a just one drug therapy in particular for the very sick people …

    america had a big big problem: without lockdown the virus do not stop is its natural life. You in america do not use preventive therapy like the Raoult’s one neither locked down your cities … How do you want to solve the pandemic? Waiting for difficult and long and many times wrong rtcs trial it is just irrational.

  56. critical p says:

    I would just like to thank Robert Clark for providing links to information i’m too lazy to go looking for again. Thanks Robert. The facts will reveal the truth.

  57. Popper says:

    A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.

    None of the patients died in the studied period and only 6 have to be admitted in conventional hospitalization area

    https://www.medrxiv.org/content/10.1101/2020.06.10.20101105v1

    1. David Young MD says:

      Now that is a weird abstract! They tell how many people were enrolled in the study and they told you in the abstract that 54 used HCQ and “the others did not.” (yes, you can do the math… but how they present it is weird). Furthermore, they don’t tell how many acquired Covid19. They just tell you in the abstract that those who were taking HCQ had “significantly less.” Why don’t they tell you the percentages? Anyone else writing an abstract would! Furthermore, the two groups were not randomly selected. So, how does that work! Furthermore 106 total people enrolled is rather small. Should have something like 500 people, but better yet, 1,000.

      And there is a good reason why. Think of it this way. There may be 20 “studies” done in various places in India where about “100” patients are looked to see if HCQ is helpful. 19 of the 20 studies show that it does not help. One of the 20 shows that HCQ helps (this study). The negative studies are not worth reporting. The one “positive” study has exciting results so that it is published. Everyone and their brother assume that the positive study is the only study of its kind done and assume that it is a meaningful results. No one, and I repeat, no one, is aware that there are another 19 studies that were negative. Nope, not buying it. Far too few enrolled people and not randomized. The study is not worth the disc space that it is stored on.

      1. Edward R says:

        Dave,

        p<0.001

        That means an extremely significant result. Anything under p<0.05 is considered as such.

        This is what would be expected as occured in Raoult's and Zelenko's findings as evidenced by Yale Professor of Epidemiology Harvey Risch PhD.

        1. Marko says:

          Dave won’t have any problem rationalizing away a p = .001 , he’ll just assume that there were 999 negative small studies in India , and only the single positive one was reported.

      2. john says:

        @David Young.

        <They tell how many people were enrolled in the study and they told you in the abstract that 54 used HCQ and “the others did not.” (yes, you can do the math… but how they present it is weird).

        In the Results statement of their abstract the first sentence reads:

        "Results: 106 healthcare workers were examined in this cohort study of whom 54 were HCQ users and rest were not."

        So, you apparently have difficulty in subtracting 54 from 106? Hint: the answer is 52.

        <Furthermore, they don’t tell how many acquired Covid19. They just tell you in the abstract that those who were taking HCQ had “significantly less.” Why don’t they tell you the percentages? Anyone else writing an abstract would!

        But the entire paper is available on the medrxiv.org web page here: https://www.medrxiv.org/content/10.1101/2020.06.09.20116806v1.full.pdf

        I understand that you apparently are a title and abstract reader and have no time to go into an actual manuscript. It took me about 30 seconds to find the answer, which is in Figure 1. Among 54 healthcare workers prophylaxed with HCQ, a covid-19 test was positive in 4 and negative in 50. Among 52 healthcare workers not prophylaxes, covid-19 test was positive in 20 and negative in 32, a highly statistically significant result.

        <Furthermore, the two groups were not randomly selected. So, how does that work! Furthermore 106 total people enrolled is rather small. Should have something like 500 people, but better yet, 1,000.

        I would love to have your help in estimating sample size requirements. You seem to just pull numbers sample size numbers out of your nose. Of course this was a retrospective study. Would a randomized trial have been better? Perhaps. But the fact is, the study, although small, found a highly statistically significant difference between the 2 groups. In such a situation, increasing sample size would be highly unlikely to change the results, all else being equal.

        <And there is a good reason why. Think of it this way. There may be 20 “studies” done in various places in India where about “100” patients are looked to see if HCQ is helpful. 19 of the 20 studies show that it does not help. One of the 20 shows that HCQ helps (this study). The negative studies are not worth reporting. The one “positive” study has exciting results so that it is published.

        True, publication bias may be somewhat of an issue. But in the current climate, negative studies regarding HCQ seem to be getting published. It's not useful to exaggerate the issue with histrionics and made up numbers (e.g. 19 negative studies to 1 positive study). Or maybe the ratio was 100:1? or 1000:1? or googol:1?

  58. An Old Chemist says:

    There’s more — e.g. a petition signed by 500,000 French doctors
    and ctizens to allow prescribing HCQ before the ICU stage.

    Editors of The Lancet and the New England Journal of Medicine: Pharmaceutical Companies are so Financially Powerful They Pressure us to Accept Papers

    https://healthimpactnews.com/2020/editors-of-the-lancet-and-the-new-england-journal-of-medicine-pharmaceutical-companies-are-so-financially-powerful-they-pressure-us-to-accept-papers/

    1. Edward R says:

      Philippe Douste-Blazy, MD, is a cardiologist and former French Health Minister who served as Under-Secretary General of the United Nations. He was a candidate in 2017 for Director of the World Health Organization.

      Dr. Douste-Blazy supports the combination treatment –hydroxychloroquine (HCQ) and azithromycin (AZ) for Covid-19 recommended by Dr. Didier Raoult. In April, 2020

      He revealed that at a recent Chatham House top secret, closed door meeting attended by experts only, the editors of both, The Lancet and the New England Journal of Medicine expressed their exasperation citing the pressures put on them by pharmaceutical companies.

      He states that each of the editors used the word “criminal” to describe the erosion of science.

      ***************
      Meanwhile as CoVid-19 rages on and sales of Remdesivir etc grow… the truth slowly begins to emerge from the fog of war…
      ****************

      “However, public health officials, academic physicians and the media – all of who are financially indebted to pharmaceutical companies and their high profit marketing objectives – vehemently oppose the use of HCQ, and use every opportunity to disparage the drug by derisively referring to President Trump as its booster”

  59. An Old Chemist says:

    There’s more — e.g. a petition signed by 500,000 French doctors
    and ctizens to allow prescribing HCQ before the ICU stage.

    https://healthimpactnews.com/2020/editors-of-the-lancet-and-the-new-england-journal-of-medicine-pharmaceutical-companies-are-so-financially-powerful-they-pressure-us-to-accept-papers/

    1. Edward R says:

      Thanks AOC… but the article you linked already said it all. It’s just the usual criminal corruption behind the anti-HCQ sentiment we are continually being bombarded with.

      The end is nigh folks…. and it’s going to get ugly.

  60. mike99588 says:

    Btw, we’re not so eager to do HCQ etc for prophyllaxis. I am interested in the early HCQ etc treatment data that are so crucially avoided by pharm phriendly studies.

    We’re happy with 10,000 iu vitamin D3, 2-4 grams vitamin C 4-5x, 30 mg zinc, 1000+ mg quercetin (onions…), 200-400 mg magnesium, 15 mg menaquinone-4 per day.

    IV C at 1000 mg C per kg body mass TID, with 50,000 iu vitamin D and more zinc+quercetin is our first standby for acute CV19.

    1. Edward R says:

      Quercetin is another known zinc ionophore like HCQ. There is a good study on how it works here…

      https://pubs.acs.org/doi/10.1021/jf5014633

      I apllaude you for your HCQ workaround with quercetin. I can’t image the pressure on those in your field to not use HCQ. If you have any info on how you arrived at the dosages it would be appreciated.

  61. Robert Clark says:

    The editors of the Lancet And the NEJM have admitted the drug companies undue influence on their publications privately:

    Editors of The Lancet and the New England Journal of Medicine: Pharmaceutical Companies are so Financially Powerful They Pressure us to Accept Papers.
    *In a videotaped interview on May 24, 2020, Dr. Douste-Blazy provided insight into how a series of negative hydroxychloroquine studies got published in prestigious medical journals.
    He revealed that at a recent Chatham House top secret, closed door meeting attended by experts only, the editors of both The Lancet and the New England Journal of Medicine expressed their exasperation, citing the pressures put on them by pharmaceutical companies.
    He states that each of the editors used the word “criminal” to describe the erosion of science.
    He quotes Dr. Richard Horton who bemoaned the current state of science:
    “If this continues, we are not going to be able to publish any more clinical research data because pharmaceutical companies are so financially powerful; they are able to pressure us to accept papers that are apparently methodologically perfect, but their conclusion is what pharmaceutical companies want.”*
    https://healthimpactnews.com/2020/editors-of-the-lancet-and-the-new-england-journal-of-medicine-pharmaceutical-companies-are-so-financially-powerful-they-pressure-us-to-accept-papers/?fbclid=IwAR3Vtty_VaPU-gS76KW-xxoqymI_YJy7AoYRaCNlr1sCEOPv9NGh9Gv00A4

    Dr. Douste-Blazy expressed this viewpoint in this interview in French:

    Lancet Bombshell – Editor Of Prestigious Medical Journal Decries “Criminal” Erosion Of Science.
    https://www.youtube.com/watch?v=2QHuIfCSsuo
    (To see English captions open up on a desktop or use the desktop option on a mobile, select the “CC” option at bottom of video window, then next to that there is the the usual gear icon for settings that will allow you to select the caption language.)

    Robert Clark

  62. Bill M says:

    Hmm, seems their dosing of HCQ was decided based on “modeling use of HCQ in treatment of amoebic dysentery”. This is somewhat strange since HCQ is not used to treat amoebic dysentery, hydroxy*quinolines* are used to treat AD, and they are not HCQ. The dosage of hydroxy*quinolines* used is 2,000 mg. The lethal dose of HCQ is 4,000 mg …

    1. EugeneL says:

      What the fuck is going on with these HCQ trials?

      1. Edward R says:

        That’s the $64,000 question.

        They are always designed to overdose, kill, fail and erroneously report common HCQ side effects as being CoVid-19 based on self reported symptoms and not tests. They are usually started too late AFTER the virus has already done irreparable damage.

        Meanwhile Philippe Doeste-Blazy a former French Health Minister informs us the editors of both the NEJM and Lancet were forced by pharmaceutical companies and global health officials to publish fake studies that proved HCQ didn’t work and was actually a killer.

        If HCQ did NOT in fact work then WHY would they even need to do that?

        1. Barry says:

          The FDA determined that oral formulations of HCQ and CQ are unlikely to be effective in treating COVID-19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks.

          https://www.jurist.org/news/2020/06/fda-revokes-emergency-use-authorization-for-2-medications-to-treat-covid-19/

    2. ghost of q.mensch says:

      @Bill M.
      Yep. Looks like one of the “Recovery” study designers, a Prof. Martin Landray
      https://www.ndph.ox.ac.uk/team/martin-landray

      apparently in error mistook 8-hydroxyquinoline antiamoebic drug ( ie 5,7-diiodo-8-OH-quinoline, or 5-iodo-7-Chloro-8-OH-quinoline) dosages for GI amoebic infections for HCQ, consequently specified giving a borderline toxic 2400 mg HCQ/day1–>800mg/day thereafter to already hospitalized very sick pts (~4x dosage that is given in the Raoult and Zelenko HCQ covid tx protocols).

      Chris Martenson discusses this colossal screw-up here (starting at ~min 34:00)
      https://www.youtube.com/watch?v=pnS4MbRribw

      It is almost as if these HCQ trials are DESIGNED to fail…

  63. Pathcoin1 says:

    The hypothesis that HCQ regimens work against COVID-19 all indicate that the medication must be used early and that it’s early use prevents progression of the disease. HCQ works by preventing the virus from binding to and entering the cell. Once the virus has done this, then HCQ will be ineffective. If we are going to evaluate something scientifically then the hypothesis should be stated and the experiment set up to test the hypothesis. To test the hypothesis all that is needed is compare a cohort treated early in the disease against one that is not treated and determine the rate of hospitalization. The could have easily been accomplished within a week or two.

    All published studies look at the disease once it has progresses to immunological dysfunction. The later stages of the disease need to be treated as such, with heavy immuno-suppression using corticosteroids or similar medications, plus treatment for coagulapathy and presumptive treatment for sepsis.

    1. drsnowboard says:

      “HCQ works by preventing the virus from binding to and entering the cell. ” so not by zinc transport to interfere with polymerase function then? Please don’t quote a molecular modelling study.

  64. henk says:

    if the trial didn’t have all these stipulations then it wasn’t really a good study.
    1) hydroxychloroquine + zinc + azithromycin have to be used together.
    2) hydroxychloroquine needs to be take on the same day symptoms appear or shortly after (?ie when testing), since anti viral drugs work best when used early on and are useless when used later on.
    3) it has to be a double blind placebo trials of course.
    4) and the p has to be at least 0.1 or better

  65. Plinny says:

    Quoted from:
    https://www.amjmed.com/article/0002-9343(83)91269-X/pdf
    Also see:
    https://ard.bmj.com/content/annrheumdis/57/10/582.full.pdf
    and:
    https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.10749

    No eye disease was detected in over 900 rheumatoid arthritis patients treated with less than 4.0 mg/kg per day of chloroquine or less than 6.5 mg/kg per day of hydroxychloroquine for a mean of about seven years. I therefore consider these dosage rates safe, since they are below the threshold of retinal toxicity. This is based on more than 6,000 patient-years of drug exposure. That dosage threshold for retinopathy appears to be 5.1 mg/kg per day for chloroquine and 7.8 mg/kg per day for hydroxychloroquine according to my studies with these compounds. The daily dosage rate, rather than total drug accumulation, seems to determine the development of eye disease. To prevent overdosage, dosing should be calculated not on the actual weight of the patient but on ideal (lean) body weight.

  66. Edward R says:

    Did anyone else notice that the fatality rates in Utah which started using HCQ early and widely are unusually low?

    15,344 cases, 6,643 open cases and only 149 deaths.

    Hmmm… I wonder what could be responsible for that. Any guesses?

    1. Marko says:

      Covid19-Projections estimates total infected in Utah to date at ~26,500 , which would put the IFR at about .5 -.6% , close to many of the nationwide estimates.

      Utah is whiter than white , so that might be a factor if the death rate is indeed lower than average, given that blacks contract and die from Covid at about double the rate of whites. Indian reservations in Utah might tend to offset that effect , however. , as reservations have been sites of some pretty bad outbreaks.

  67. mike barnes says:

    Treatment with Hydroxychloroquine Cut Death Rate Significantly in COVID-19 Patients, Henry Ford Health System Study Shows July 2 2020

    ops……………………..

    1. Marko says:

      Link to the paper :

      https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext

      Not that any opinions will change. Trump promoting hydroxychloroquine was the kiss of death.

  68. john says:

    A fairly large retrospective trial done at the Henry Ford Health System (2500 patients) looking at HCQ alone, azithromycin alone, the combination, or neither of these two drugs, was just published in the Int. Soc. Infectious Diseases Journal.

    Here is the paper:
    Arshad et al (Henry Ford Hospital Study)
    https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext

    Results
    Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4-10 days), median age was 64 years (IQR:53-76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3-53). Overall in-hospital mortality was 18.1% (95% CI:16.6%-19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%-23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%-15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%-30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%-31.0%])​. Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 [95% CI:1.9-3.3]), white race (HR:1.7 [95% CI:1.4-2.1]), CKD (HR:1.7 [95%CI:1.4-2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1-2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4-3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p < 0.001).

    And an editorial discussing the limitations of the study:
    editorial
    https://www.ijidonline.com/article/S1201-9712(20)30530-0/fulltext

    Press release from Henry Ford:
    https://www.henryford.com/news/2020/07/hydro-treatment-study

    No large adverse safety signal from HCQ re torsades although the QTc was monitored.

    1. Christopher says:

      There is a serious problem with patient age in the Henry Ford study. Look at Table 1 from the PDF (paper-page 22, digital-page 24):
      https://www.ijidonline.com/action/showPdf?pii=S1201-9712%2820%2930534-8

      No med group: Median age: 71 years old, Mortality: 26.4%
      AZM group: Median age: 64 years old, Mortality: 22.4%
      AZM+HCQ group: Median age: 62 years old, Mortality: 20.1%
      HCQ group: Median age: 53 years old, Mortality: 13.5%

      I don’t see how the researchers concluded that “oh, it was the HCQ that caused the lower mortality, not the 18 year age difference”. Age also explains why AZM+HCQ did much worse than HCQ alone (there’s a 9 year age gap between those groups).

      Am I missing something fundamental here, or are this paper’s conclusions the garbage that they look like?

      1. Tony M says:

        Chris, good pickup. That must be a typing error in the table. Should read medium age “64 (53 – 74)” ie. the medium age has to be between the 2 figures in brackets as they represent the Medium (IQR). Also mean age was 63.2.

        “The Cox regression result for the two propensity matched groups (table 4) indicates that treatment with hydroxychloroquine resulted in a mortality hazard ratio decrease of 51% (p=0.009)” The characteristics of this matched group are detailed in table 3 on page 28.

        Regards

        Tony

        1. Tony M says:

          Should read medium age “64 (53 – 74)” that is for the HCQ Alone Group

        2. Christopher says:

          Thanks, that makes more sense. It’s still a big age difference between the two arms, especially towards the older (and more likely to die) end of the distribution.
          None: median:71, 25percentile:56, 75percentile:83
          HCQ: median:64, 25percentile:53, 75percentile:74
          (True, the raw distribution isn’t directly used as results. Unfortunately, most coverage I’ve seen quotes the “13% vs 26%” from the Table 2 directly).

          Age is muddled by their model in a way that significantly favors the HCQ group. The model throws away the numerical age and only retains the age as a category of “65 and older” versus “younger than 65”. From the perspective of the model, the top quartile of both groups is considered to be the same age, because they are both “65 and older”. But for the None group, the 75th percentile is 83yo, while for the HCQ group, the 75th percentile is 74yo. Mortality is much (much!) higher at age 83 than at age 74, but this model treats those ages as the same.

          The other thing that seemed strange about the paper is that the hazard ratio for white race was 1.738 (even higher than that for chronic kidney disease!). This suggests that mortality for whites is almost twice mortality for non-whites (which mostly means blacks in the context of this data). This is the opposite of every other finding about race and mortality, but yet it gets no discussion.

          So, to me, the paper still looks to be wrong in its conclusions. I really wish we had the raw data, because that would quickly settle these discussions.

  69. john says:

    Fenofibrate may be useful in the treatment of COVID-19 based on in vitro data.

    https://www.timesofisrael.com/existing-drug-may-downgrade-covid-threat-to-common-cold-level-jerusalem-study/

    Only in vitro evidence to-date, but still interesting:

    He said the virus interferes with the ability of the body to break down fat, and fenofibrate jump-starts this process. “The interesting thing about our study is that fenofibrate actually binds and activates the very site on the DNA that the virus shuts down — a part of our DNA that allows our cells to burn fat,” he stated.

    “Virus infection causes the lung cells to start building up fat, and fenofibrate allows the cells to burn it.”

    The restart of the process is swift, he said, comparing it to “when the plug is removed from the bath tub.”

  70. Brad says:

    Man this is better than reading a sports section!

  71. Fintan Stack says:

    A new study from Belgium on HCQ, results appear promising
    https://www.sciencedirect.com/science/article/pii/S0924857920303423

  72. Ornery Critter says:

    Reposting a post from An Old Chemist: 30 July, 2020
    “The following website lists over 100 studies published to date on HCQ and Covid-19:
    https://c19study.com/
    These studies have been classified into four categories depending on the timing of the HCQ treatment:
    PrEP – used as pre-exposure prophylaxis
    PEP – used as post-exposure prophylaxis
    Early – patient treated at an early stage of Covid-19
    Late – patient treated at a late stage”
    This is an ongoing study. Currently it lists only 88 studies of which 50 are peer-reviewed. Here are the summary results for percent positive results:
    Prep, Pep and Early: 100%, Late: 60%.
    Pretty good!
    Although I personally believe the Sars Cov 2 threat for healthy people has been greatly exaggerated, I’m still taking zinc + quercetin supplements and plan to do so all winter. Might help against the cold and the flu, too.
    Vax no thanx.

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