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The Latest Coronavirus Clinical Trials

Time to catch up with the latest clinical news in the field. The big story this morning is apparently some real data out of a controlled trial of chloroquine from China. There have been anecdotal reports, but to the best of my knowledge we have seen no actual numbers. These are not exactly from the peer-reviewed literature, either, but were unearthed by market analyst Umer Raffat at Evercore/ISI. It’s another small study, understandably, with 15 patients in the control group and 15 randomized to a treatment group getting 400mg/day of hydroxychloroquine for five days. At the end of this period, the treatment group showed 13/15 negative for viral RNA via throat swab. . .and the control group showed 14/15 negative. Other parameters were also so similar between the treatment and control groups as to be uninterpretable. So those numbers are unfortunately not too useful. It’s tempting to run with a “hydroxychloroquine fails” take, but we can’t even say that with such a strong control group response. It’s basically a blown trial that can’t tell us anything – we have no idea what an earlier endpoint would have told us, for example, although I have to note that this is about the time course of treatment in the widely-discussed Marseille study. We need more and better numbers (which is the same conclusion as the authors of this study have), and I hope that we get them soon.

Now for the rest of the trial news. This study from China isn’t large either: 7 control patients, 21 getting a lopinavir/ritonavir combination, and 16 getting the Russian antiviral compound umifenovir (Arbidol). That second regimen showed some efficacy against SARS and was certainly a logical thing to try, but it has already failed one trial, and by gosh it failed this time, too: no benefit, and a trend towards more adverse events. It’s hard to see why this regimen should have more work done on it, to be honest. Now, umifenovir I hadn’t heard of, and I can’t say that I’m in love with its structure, either. Those alpha-aminomethyl phenols are often trouble; they can eliminate to form a reactive quinone methide which can go on to do all sorts of things. I have no problem with covalent drugs per se, but quinone methides are, I think, more towards the hot end of the spectrum and more liable to go for the first nucleophile they see. As far as I can see, the drug’s targets are unknown – it seems to affect the earlier stages of viral entry and has been tried against a wide range of viruses (DNA and RNA). It has sold very well in Russia and China over the years, but is hardly approved anywhere else, and apparently even the Russian Academy of Medical Sciences came out in 2007 saying that there was no evidence that it was useful. It wasn’t this time – no difference from the control group.

That was a small trial, to be sure, but the drug shows up in this trial as well, with 120 patients getting Arbidol and 116 getting favipiravir, which I’ve also mentioned before. That first trial looked as if there might be some benefit, but it was open-label with only 35 patients. In this case, we don’t have a control group, and all that we can say is that favipiravir looks better than Arbidol. If that smaller trial above turns out to be accurate, then the latter is pretty much the same as getting nothing, in which case perhaps favipiravir helps. Mechanistically I have trouble seeing how it can, though, and have since the beginning of this whole epidemic, since it barely does anything in the in vitro assays. It definitely has some adverse reactions as well (liver function tests, psychiatric symptoms, and others), but a patient in bad shape would, you’d think, rather get this drug than nothing.

There’s a lot of noise in this area, of course. According to this tweet, the Chinese State Council, for example, has apparently announced that Traditional Chinese Medicine has a 90% success rate in treating the virus. What I’m supposed to make of that, I do not know – I hope that this is a mistranslation of earlier reports that 90% of the outbreak patients have been given some form of TCM, and even that number is hard to evaluate. The Chinese government has of course been promoting this stuff for some time now, and I suppose that we can’t expect them to ignore an opportunity like this, but geez. Here’s the South China Morning Post on the issue. Papers on this stuff are already appearing, and already being ripped to pieces for having things like duplicated data in them. Interestingly, it appears that earlier WHO guidelines recommended against herbal remedies for the Covid-19 epidemic, but that language appears to have disappeared, in what some speculate is pressure from the Chinese authorities. My own opinion is simple to state: bring clinical data or shut up.

We still have several remdesivir trials waiting to read out, and of course, everyone’s object of interest: hydroxychloroquine (and its combination with azithromycin). The full paper on that one has published, though, and Leonid Schneider noticed that the curves for the hydroxychloroquine/azithromycin treatment group are different (and slightly better looking) than those in the preprint. Others have gone through the data tables and found that the evidence is not as solid as it might seem from just looking at the now-famous chart, either. My take continues to be that this work definitely justifies a larger, more controlled study, but that it also is nowhere near large enough or well-controlled enough to prove anything by itself. I understand that many physicians are going ahead and giving patients the HCQ/AZ combination anyway, and I can see why they’re doing that if they believe that the chances of benefit outweigh the chances of harm. But we don’t quite know if they do, to be honest. Giving it only to people who are in bad shape (already on ventilators) is probably the best way to split that difference, and from what I’m hearing, that’s the usual call that physicians are making. I hope it does some good, and I hope that we find out as soon as possible if it does.

99 comments on “The Latest Coronavirus Clinical Trials”

  1. zeus Zhang says:

    Thanks for the information. lopinavir/ritonavir or umifenovir (Arbidol) do not seem to have any significant impact. As for chloroquine or hydroxychloroquine, there seems to be some benefit, most likely for early application. However, there are patients getting worse on HCQ from both French and Chinese trials (death or ICU). Unless we can identify a marker to know the group of patients who might be adversely impacted, caution is warranted.

  2. In Vivo Veritas says:

    Stop trying to be such a voice of sanity/reason, Derek. My president says there’s no risk, so I’m taking ~6 grams of chloroquine a day. What could go wrong????

    1. cirby says:

      Maybe you should take it up with the doctor who prescribed you such a bizarre dose of the stuff?

    2. An Old Chemist says:

      My Google searches tell me that for malaria for an adult 1.0 gram dose given in two lots per day is a drug, and 2 grams is a lethal dose!

      1. Charles H. says:

        But with enough gin to make it tolerable. After all, alcohol also kills the COVID-19 virus.

        Which beings to mind the fogging pictures. Too late to fit the flow, but if I were designing fog, I’d use dilute hydrogen peroxide. IIRC 0.1% is supposed to be better at sanitizing against it than 20% alcohol, so make the fog out of 0.3% hydrogen peroxide, and a smidge of soap or detergent to aid penetration. I first thought of ethanol, but that’s really too volatile to be useful.

        1. Olandese Volante says:

          A fogger with 60% ethanol could double as a flamethrower, which might be effective 😉

      2. cirby says:

        Two grams is not a lethal dose for a normal adult.

        Two grams CAN cause problems for people with severe heart conditions if not monitored. As can a whole lot of other drugs.

    3. C says:

      You joke, but scared elderly people actually believe the words Trump says:
      https://www.cnn.com/2020/03/23/health/arizona-coronavirus-chloroquine-death/index.html

      Where is Luysii’s Trump apologism?

      1. loupgarous says:

        No politician is the Fount of All Evil. Not Trump, not the Clintons, not Obama, not either of the Bushes. Once we get over hating as a substitute for thought, we’ll have conquered a worse plague than coronavirus.

        1. Jason says:

          ^ this for heaven’s sake. Stop with the childish overreactions to everything the prez says

          1. Ogamol says:

            When Obama said reasonable things, certain folks said “This is an outrage”, yet Rush Limbaugh saying unreasonable things got “He just misspoke” from those same folks. Now Trump says unreasoning things, and those same folks say “Stop being childish about what he said”. You ought to stop caring about the source and look at what’s actually said. Then think about what was said.

        2. Kim Violanti says:

          Well said!!!

  3. MandyM says:

    Umifenovir looks like a lesson for students to in functional groups.

  4. Carrie says:

    I’m guessing that figure about Chinese traditional medicine is the survival rate for patients in whatever group looked at who were given traditional medicine in addition to modern medicine, without a control group.

    1. Anonymous says:

      Carrie, “traditional medicine in addition to modern medicine, without a control group.”: I had a coworker from China who was homozygous hyperlipidemic. She had a heart attack during childbirth (here in the USA) in her early 20s and, after extensive testing, that’s how they found out. She was participating in a clinical trial for the hyperlipidemia but she was also taking traditional Chinese medicines on her own. I asked her if she told the clinicians that she was also using Chinese TM and she said no. I encouraged her to tell them but she didn’t. I wonder how many clinical trials are confounded that way?

  5. Lane Simonnian says:

    Here is probably the most detailed (and relatively balanced) review of Traditional Chinese Medicine for SARS-CoV-2.

    https://www.ijbs.com/v16p1708.htm

    These are the theories behind the potential effectiveness of ginseng, for instance: prevents over-immune reactions (“cytokine storms”), maintains normal immune reactions, reduces oxidative damage to lungs, inhibits viral replication, inhibits viral docking, directly kills the virus. Of these, the first three have the most evidence behind them.

    https://www.sciencedirect.com/science/article/pii/S1226845319303264

  6. Cb says:

    after a single oral administration of 200 mg of umifenovir (arbidol) in volunteers 33 metabolites were identified including sulfoxidation, dimethylamine N-demethylation, glucuronidation and sulfate conjugation, but NO reactive quinone methide formation as predicted by Derek (and which metabolite I also would predict); so interesting med chem question for students and much appreciated if they predict (incorrectly!?) the reactive quinone and its glutathion adduct. See: 10.1128/AAC.02282-12

    1. ScientistSailor says:

      It’s unlikely you would find that metabolite. It would be stuck to something like a protein or glutathione…

      1. Cb says:

        Probably, but in that case we also should consider this reactive metabolite of Arbidol to inhibit irreversibly the viral papain-like cys protease. To this end it is interesting to study the anti viral activity of the reactive benzoquinone-imine metabolite (NAPQI) of acetaminophen/paracetamol, which will be formed in large quantities if people take a couple of grams per day. In a very optimistic scenario NAPQI inhibits the corona papain like protease and jumping to conclusions: among them the patiens with mild symptoms. Imagine good old (toxic) acetylamidophenole, the wonder drug (Von Mering 1893, Antipyretica)

    2. Barry says:

      We use glutathione in vitro as a surrogate protein when trying to preview metabolism using liver microsomes. But in vivo, that quinone methide might end up stuck to any of a thousand “targets”.
      You’d need to do a mass balance and probably a radioisotope tracer to learn its fate/rule it out

  7. John Wayne says:

    I’d like to see an Azithromycin only arm in follow up clinical trials. I thought that the hydroxychloroquine only arm looked pretty weak in the initial data; if it doesn’t do much we should get it out of there.

  8. WFH in SF says:

    At least one person is dead due to self-medicating with chloroquine (full article linked in name). According to his widow:

    “Trump kept saying it was basically pretty much a cure,” the woman told NBC. She said her advice for people would be, “Don’t take anything. Don’t believe anything. Don’t believe anything that the president says and his people … call your doctor.”

    1. Cedar L Sanderson says:

      I may not have a PhD, but I am pretty sure chloroquine phosphate is not the same as hydroxychloroquine.

    2. KazooChemist says:

      I do not recall the President telling anyone to self-medicate with chloroquine. I also do not recall him advising anyone to ingest fish tank cleaner like the individuals in the story you have linked to.

    3. cirby says:

      You know, when you post incredibly stupid stories about incredibly stupid people, thinking it’s a “dunk” on President Trump, all it does is make him look better after normal folks look up the actual story and find out what really happened.

      That’s why his approval rating is currently going UP.

      1. c says:

        What troll farm do you bugs crawl out of?

        You’re going to blame frightened elderly people instead of the fear-monger himself?

        If those were your parents or it was Obama making that statement you would be absolutely outraged.

        You Trump apologists have become totally brain washed.

        1. TC says:

          If you don’t let kids kill themselves eating Tide Pods, they grow up and eat fish tank cleaners.

    4. CanWeTakeABreakPlease says:

      Ummm, the President did not say “go and guzzle 20x the usual dose, but use fish tank treatment which is a different chemical, don’t consider any contraindications such as age and pre-existing cluephobia, and while you’re at it don’t consult with an MD who might have your chart handy and can determine if this treatment is suitable for a horse-sized mammal, much less you.”

      Other than that, it’s still not what the pres said.

      1. Wanting a real accountable leader says:

        Chloroquine phosphate is another antimalarial compound closely related to hydroxychloroquine. It is slightly more toxic and is apparently used in fish tanks to control parasites, not some kind of bleach cleaner. Hydroxychloroquine has toxic side effects as well, hardly surprising.

        True, he did not actually utter those words ‘take this’. But the victims had been listening to his touting of the compound as good, and basically listened to ‘their leader’. This does not excuse their stupidity but Trump’s grandstanding certainly does not help. That’s the danger of adopting a careless attitude and using your position to sound like a hero when you have no understanding of the science.

        1. Mike Smith says:

          You do realize that the President has to balance available information while trying to give people hope and not panic right? As bad as the the virus is, a collapse of society due to excessive media panic and fear mongering could have a much higher death toll. If people feel more hopeful they will be more likely to take better care of themselves and adhere to social distancing guidelines. Hydroxychloroquin may not be a miracle cure but there are very sick patients who have had good results with it. Some doctors who are treating CoVid 19 patients are taking it to protect themselves.

  9. Daniel Barkalow says:

    Traditional Chinese medicine has a 90% cure rate, as compared to the 93% cure rate in the control group?

  10. johnnyboy says:

    I don’t see how any antiviral therapy could possibly make a dent in this. By the time the signs are clinical, the virus has gone through the tissue and caused its damage, which from the pathology reports appears to be an ARDS type lesion, likely due to injury/killing of the type 1 pneumocytes lining the alveoli. Treating a symptomatic patient, likely with advanced signs, is closing the barn doors after the horse is in another state. The patients struggling to breathe have alveolar spaces full of fluid, fibrin and inflammatory cells, not virus. Assuming you have an antiviral that can actually decrease viral entry into cells or replication, for it to have an impact you’d need to administer as a preventative, or to patients that have just turned positive but are still asymptomatic – and there is no way you’ll be able to produce enough pharmaceutical bulk to do that for hundreds of thousands (or millions) of people yet to be affected. All efforts should be directed toward vaccines, not antivirals.

    1. cirby says:

      It’s also supposed to work as a prophylactic therapy, and keeps the virus from reproducing.

      The other part of the most-effective claimed therapy is azithromycin, which (supposedly, according to at least one study) has some effectiveness at reducing the overproduction of mucus.

      So you have a drug that stops the virus, and a drug that clears out the airways in the lungs.

    2. rtah100 says:

      Er, johnnyboy, chloroquine and hydroxychloroquine are both antimalarials, prescribed by the million for prophylaxis. If they can prevent SARS2 infection, it will be a scalable solution.

    3. eub says:

      If we can scale up testing capacity to test everybody with CoV-compatible symptoms, we might be able to administer a hypothetical effective antiviral before the lung damage has been done, which seems to be about a week after early symptoms.

    4. MagickChicken says:

      Patients still shed up to three weeks after diagnosis. Seems like even if it isn’t necessarily helping the pathology, it would still help reduce spreading from the institutionalized.

  11. Tim Shi says:

    Here is a reasonable explanation: Traditional Chinese medicine has a 90% cure rate v.s. to the Covid-19 self-cure group, which is about 80% of patients with minor symptoms could be self-recovered/cured in anyway, for instance, drinking water and sleeping well or watching TV or gaming, etc(Be Happy!)… That is the basically control group in definition.

  12. Tim Shi says:

    If anyone might have seriously interesting in discussion of Traditional Chinese medicine to cure this Covid-19, we can organize a group to talk about it.

    1. Jonathan Cardoso-Silva says:

      I have experience with QSAR and some computional chemistry modelling. If that helps, I’d be glad to be in such group. Whatever I can do to help.

    2. milkshake says:

      traditional Chinese medicine is a fairly modern invention, and the “theory” behind it is a pseudoscience scam perfectly comparable with homeopathy. Mao had traditional Chinese medicine re-invented and actively promoted when he realized his country could hardly afford western medicine, and people were going to use village remedies anyway. This was the best they could do at the time.

  13. An Old Chemist says:

    Top COVID-19 aspirants chloroquine, AbbVie’s Kaletra and a flu drug disappoint in clinical tests

    https://www.fiercepharma.com/pharma-asia/top-covid-19-aspirants-chloroquine-abbvie-s-kaletra-and-a-flu-drug-disappoint-clinical

    1. steve says:

      Considering that 93.3% of the control patients in the hydroxychloroquine study cleared virus it’s hardly surprising that the drug didn’t show an effect. It needs to be repeated in a cohort that is more at risk.

      1. Giannis Zaxarioudakis says:

        Prophylaxis prophylaxis prophylaxis. Antiviral drugs are much more likely to work for pre exposure and post exposure prophylaxis than when the virus loads have skyrocketed. There are some studies being done for prophylaxis. If it works it will be a gamechanger.

        1. charlie says:

          Yep, that’s the ticket.

          And I suspect a lot of the doctors stocking up. One a day for a month isn’t fun but better than being out for 14 days.

          The only problem is you’d assume the medical staff is getting massive viral loads.

  14. BrowserDoesntSaveThisField says:

    On a more serious note, tx to the blog and the informed posters for providing current info, less any spin or journalist fog. I can’t decipher that for myself, but figure that (mostly) professionals chatting amongst themselves are providing the most recent state of affairs.

    As someone who finds himself involuntary in a high risk group and in the now world center of both infection and transmission, and among people who hoarded masks and now wear them over thick beards, I want and need to know what happens if I get viral pneumonia from the virus of many names. If I had a place to go outside of Rome, umm, Empire City, out I would be.

  15. Rock says:

    We used to have a lot of analogs that looked like umifenovir in our screening deck for some reason and they very often showed up as hits in HTS screens.

  16. PyBOP says:

    Prof. Christian Drosten, a CoV specialist of Charitee/Berlin was discussing the French study recently in a German podcast. Apparently, one of the major issues with the design of these studies is the choice of the “viral RNA in throat swab” endpoint. According to him, virus load in the throat decreases rapidly in all patients, even severe cases, within the first week after infection. This parameter has no correlation with the actual clinical outcome. He was calling for measurement of virus load in the lung or, preferably, clinical endpoints like mortality/time to discharge.

    More from him here (German): https://www.youtube.com/watch?v=3O6jU6VZRH4&list=PLkKON9te6p3OpxqDskVsxXOmhfW0uPi1H&index=4

    Or read the transcript: https://www.ndr.de/nachrichten/info/coronaskript134.pdf

    1. Hey.

      regardless to the subject you got me curious on why u cal yourself PyBOP.
      its a critical mass of our core business and id love to know if its used for anything to do with COVID 🙂

      thanks.

  17. Christophe Verlinde says:

    Latest in NYTImes: “States Say Some Doctors Stockpile Trial Coronavirus Drugs, for Themselves”.

  18. Ashley Carter says:

    What I found most troubling about the hydroxychloroquine study was that there were originally 26 people given the drugs, but 6 had to be excluded (3 were moved to the ICU, 1 quit due to side-effects, 1 left, and 1 DIED). No controls had to be excluded. To focus on the positive outcome of the 20, while ignoring the fact that it seems to have had dramatically bad effects on 4 of the original 26 (a 15% complication rate) looks like cherry-picking data and dangerous optimism at its worst.

  19. loupgarous says:

    “It’s another small study, understandably, with 15 patients in the control group and 15 randomized to a treatment group getting 400mg/day of hydroxychloroquine for five days. At the end of this period, the treatment group showed 13/15 negative for viral RNA via throat swab. . .and the control group showed 14/15 negative.”

    Other possible explanations for this really odd set of outcomes – “were the patients correctly diagnosed before entry into the trial? Are we sure the whole study population were infected before entry?”, “Did both arms get the same medication by mistake?”

    Or a real outlier of an explanation – “Are these people infected with an hitherto-uncharacterized virus – cross-reactive with the virulent SARS virus, but less virulent or with a dramatically different clinical course?” (that happened at the Hazelton primate labs, Reston, VA – the Army biodefense labs at Ft. Detrick agreed to look at tissue from monkeys which had unpredictably dropped dead, expecting to see evidence of heat stress or something else, but found instead on EM viral particles with the characteristic “shepherd’s crook” and “loops” of Ebola, and tissue seropositive for Ebola!).

    Weird stuff like this is what sends people from the study staff flying to affected study sites to determine why grossly counter-intuitive or unexpected data (not leading to one of the foreseen endpoints) exists – which doesn’t mean taking an eraser to some CRFs, but reviewing the charts of the patients involved and doing everything else necessary to explain the anomalies.

    The charts of that particular study’s patients are worth revisiting, because something very odd happened. Probably good-old-fashioned sloppiness.

    1. loupgarous says:

      Oops, again. After

      “the Army biodefense labs at Ft. Detrick agreed to look at tissue from monkeys which had unpredictably dropped dead, expecting to see evidence of heat stress or something else, but found instead on EM viral particles with the characteristic “shepherd’s crook” and “loops” of Ebola, and tissue seropositive for Ebola!”

      I should have added “But what they had on their hands was what we now call “reston virus”, which cuts crab-eating monkeys down like a scythe through wheat, but isn’t associated with remarkable signs of illness in humans (though they can catch it and it’s pretty infective in them, too – just not pathogenic). Good thing, because the first thing the scientists at USAMRIID did on unwrapping serum samples was “pop” the vial and take a sniff (this was before they found out the virus in there was structurally and serologically almost identical to Ebola zaire).

  20. Rubidium says:

    What’s the update on drinking cow urine?

    1. Jack says:

      Ask the president? It may get more expensive than milk.

    2. Stub says:

      The results were….piss poor.

      1. Daniel Jones says:

        Ba-rum-bum!!

        Oh, all you people getting mad at folks bashing Trump? Forget it. The problem is he offends on so many levels that people use an egregrious moment to vent the overall pressure.

        1. Lodibran says:

          Inject patients with bleach or hit them with a burst of ultraviolet light, the POTUS has just mused.

    3. loupgarous says:

      I’m curious whether anyone’s read up on Morarji Desai and decided to save on vitamin water with eight ounces of “self-urine therapy”. While “traditional medicine”, ayurveda, et cetera are back in vogue….

    4. An Old Chemist says:

      @Rubidium: Cow urine is a disinfectant and cow dung has health/environment benefits. At the Amazon site, you can order both of these:
      https://www.msn.com/en-us/news/world/bizarre-coronavirus-remedies-suggested-by-indian-politicians/ar-BB10F1pe

    5. Yarodur says:

      Cow urine… mmm… OMG. Ulinastatin (https://en.wikipedia.org/wiki/Ulinastatin) – urinary serine protease inhibitor (so would act against the main viral protease of SARS-CoV-2); clinically approved in Japan, South Korea, China, and India.
      “In China, where it is approved to treat acute pancreatitis, chronic recurrent pancreatitis and ACUTE CIRCULATORY FAILURE…”, ” In India, where it is approved to treat SEVERE SEPSIS and acute pancreatitis…”.
      Am I dreaming?

      1. Derek Lowe says:

        The main viral protease is a cysteine protease, not serine.

        1. Yarodur says:

          I think out of three viral proteases two are cysteine ones, but the main one is a chymotrypsin-like serine protease, if I am not mistaken. Furin, which facilitates viral entry, seems to be a serine protease, too. Cathepsin L1 needed for the viral release from endosomes is a cysteine protease though. So ideally would be to use blockers for the both families of proteases.

  21. DTX says:

    To add to Milkshake’s comments: For those of you wondering the level of “science” underlying TCM, have a look at the China Daily. You could say “It’s just a newspaper.” However, this is the OFFICIAL government newspaper that most foreign hotels give to guests. It’s printed in English & Chinese specifically so Westerners can understand Chinese issues.
    https://covid-19.chinadaily.com.cn/a/202003/21/WS5e7543eaa310128217280de5.html

    For those who don’t have time to click the link, the article explains the “Theory of TCM”: TCM views a patient’s condition as a reflection of the interaction of 5 elements of nature: wood, fire, earth, metal, and water.” The quote in the article of the President of Tianjing University of TCM is also revealing.

  22. cynical1 says:

    So is your issue with favipiravir that it appears to inhibit RNA-dependent RNA polymerase which I would guess that Covid-19 has one since other coronaviruses have one? Or the fact that there does not seem to be robust in vitro activity?

    Given that I saw reasonable in vitro antiviral effects with a HIV protease inhibitor published against SARS which made no sense given that corona viruses don’t encode an aspartyl protease to inhibit, I would guess that the in vitro antiviral activity may not translate to in vivo activity. And the in vitro assay may just suck. I worked with HIV, HPV and EBV. The HIV assays were very useful to predict in vivo activity (in humans). We had no freaking idea what the in vitro activity with the other two viruses meant. (Never got a drug either.).

  23. Jack says:

    All old cultures and civilization have employed traditional herbal remedies throughout histories and so is the west. Often these work as good as Aspirin on cancer, yet they provide some sort of comfort the same as a prayer to a believer. Any thing that does not stand the scientific method would fail and only gives false hope.

    1. li zhi says:

      I believe it has been solidly demonstrated that hope leads to better outcomes. So, some ‘magical’ material or intervention which generates hope would be expected to improve outcomes (slightly).

  24. Lane Simonian says:

    For a more historical view of Traditional Chinese Medicine:

    https://www.britannica.com/science/traditional-Chinese-medicine/Bian-Qiao

    For me, this is the questionable part:

    “An understanding of the essence of various herbal components gives the TCM practitioner a way to create a healing effect that reaches beyond the chemical composition and physical properties of the herbs.”

    The key instead is the chemical composition of the herbs and the effect that these chemical compounds have on the human body.

    1. Dave Kielpinski says:

      Well, so much for the Britannica’s credibility. That was quite an article.

  25. wkw says:

    Teicoplanins… glycopeptides — should and prob soon will be COVID 19 trials.

    Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19?
    https://www.sciencedirect.com/science/article/pii/S0924857920300947

  26. one more says:

    https://www.medrxiv.org/content/10.1101/2020.03.21.20040691v1

    “Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial” Only 17 patients

  27. Richard Bernstein says:

    This should be an easy set of trials to do. Tons of patients. An objective outcome measure (viral load or detectability), available drugs, short treatment period. We could have a thousand person trial done in 2 weeks of HCQ with or without AZ; and I hope the redemsivir trial is done soon too.

  28. Michael James Baranowski says:

    Jack and Lane,
    I agree however I must temper by agreement with this we all have biases and cherry picking in our data all cultures have a word stated certain practices will result in a better outcome however it is only through the scientific method in current understanding of how chemicals and Other things react that we are able to have a grasp on our reality as a bitch I wonder what study if any is being done on interferon

  29. p00etr says:

    Can anyone comment on this article?:
    https://blogs.mediapart.fr/ninhursag/blog/200320/coronavirus-successful-high-dose-vitamin-c-treatment-patients

    Apparently the Chinese doctors tried high doses of i.v. Vitamine C somewhat sucessfully without any side effects, but I am very doubtful about this, it almost seems like it’s too good to be true.

    1. DTX says:

      Your skepticism is appropriate. First, the study wasn’t blinded and it didn’t have a placebo group (untreated) who didn’t get the megadoses of Vitamin C. Also, the blog notes “There were no side effects reported from any of the cases treated with high dose IVC.”

      A clinical trial of 50 moderately or severely patients to have ZERO side effects is unheard of (it’s likely unheard of even in a healthy population of 50 people). Even if you just gave patients sugar pills and they thought you were giving them drugs, they would report headaches, stomach aches, and a multitude of other effects. The fact that zero were reported suggests the researchers were either asleep during the trial or didn’t bother to record adverse events. (adverse events are recorded even though the researcher may think the effect isn’t causally related to the treatment)

      1. Susan Jones says:

        For some reason people don’t want to believe that a treatment that is so inexpensive can work. Perhaps it is because there are no drug companies promoting this treatment because there isn’t much money to be made in IV vitamin C.
        My father, Paul Honan, MD, an ophthalmologist, was very impressed with the effectiveness of vitamin C for his patients and himself. He routinely took about 10 g per day orally. Some of that was liposomal or lypo-shperic vitamin C. He used IV vitamin C for patients and for himself when needed. Most animals can make their own vitamin C and make more of it when they are sick or injured, but humans cannot. They must obtain it either orally or intravenously.
        The only side effect I’m aware of with oral vitamin C is diarrhea when a person has taken more than his body needs. The sicker someone is, the more vitamin C he needs, and the more he could take before reaching bowel tolerance.
        I can totally believe that there were no side effects for these very ill patients from the IV vitamin C. They only were give 12 g per day. They could probably have recovered even more quickly with 50 or even 100 g.
        If I or anyone in my family becomes ill with COVID-19, we will take vitamin C tablets and lypo-spheric vitamin C. If that isn’t enough, we will talk with sympathetic physicians who will prescribe IV vitamin C, so that we can quickly get well.
        I am saddened every day to hear of all the people who are dying from COVID-19 when so many could likely be saved if doctors would try really high doses of IV vitamin C to help them. I just don’t understand why doctors won’t try using high doses of IV vitamin C. It won’t harm them and would likely save their lives. They can’t just use a low dose such as 90 mg; it has to be 12, 25, 50 or 100 grams.

    2. Jim Hartley says:

      To be clear, Mark Levine and colleagues established in 2004 (PubMed PMID: 15068981) that vitamin C must be administered intravenously to reach pharmacologically useful (mM) levels. Giant oral doses maxed out at 0.2 mM.

  30. Alan Goldhammer says:

    When I was at PhRMA we conceived of and funded an Observational Medical Outcomes Partnership. It continues now as the Observational Health Data Sciences and Informatics (OHDSI) international community. This group continues to carry out the original OMOP mission of developing new tools for data gathering and surveillance. They are spending all of this week looking at COVID-19 issues in a virtual symposium as their international meeting was canceled (see the forums at: https://www.ohdsi.org/ )

    I posed yesterday about looking across data sets for patients currently being treated for lupus and rheumatoid arthritis with the two chloroquinine drugs to see if there is any protection against COVID-19 infection. This is under discussion but such studies are difficult to do outside of HMO settings who have linked pharmacy/clinical information. This is exactly the type of study we anticipated doing back in 2005 when we came up with the business plan.

    1. Jim Y says:

      Alan Goldhammer – that’s an excellent idea. I don’t know if the U.S. keeps that kind of data. I’ve heard that the Netherlands does. No idea who to contact though. But that brings up the point that the US should be storing meta-data. Data without people’s identity so we can do useful studies like you suggested.

      1. loupgarous says:

        The US is very much in the “storing metadata” business. Gargantuan digital storage farms exist all over run by NSA and other three-letter spy shops. Eventually, the bigger medical institutions (Ochsner here in the Gulf South, Humana, etc) have the sort of readily interrogatable patient charts you’re thinking of. I’d be surprised if there weren’t at least fledgling efforts by those folks and their university partners in using metadata for epidemiology and other things. Repurposing would be a lot easier if everyone’s charts were interrogable that way.

  31. Molecules R Us says:

    Is anyone looking at rupintrivir? I can’t see any sign of a trial, but it could be expected to be more useful than many of the very peripheral in silico hits currently being touted.
    https://www.clinicaltrialsarena.com/projects/ag7088/

  32. steve says:

    Just wondering what people think about this use of high dose intravenous Vitamin C, supposedly based on some results in Wuhan. Any possibility this could actually have a beneficial effect? https://nypost.com/2020/03/24/new-york-hospitals-treating-coronavirus-patients-with-vitamin-c/

    1. KazooChemist says:

      Se the posts on this above yours.

  33. Anon says:

    Hira Nakhasi of the FDA lab of emerging pathogens needs to resign. He consistently has advocated dialing back the federal response to viruses.

  34. Amanda says:

    There are also some interesting thoughts on anti-inflammatory therapy. I have not seen any data on how many patients that are ill from covid-19 actually meet criteria for cytokine storm. But if the inflammatory response is what drives a lot of the illness then options such as actemra or anakinra or just plain steroids make sense:
    https://www.pmlive.com/pharma_news/fda_approves_roches_actemra_covid-19_trial_1329887?SQ_DESIGN_NAME=2&

    I am a physician not employed or paid for by pharma

    1. loupgarous says:

      Some published reports on fatalities in high-risk Covid-19 patients mention exacerbation of the pneumonia associated with late-phase illness after administration of steroids. However’s it’s speculated that azithromycin’s use with chloroquine and hydroxychloroquine is partly owing to its anti-inflammatory properties.

      (I’m neither a physician nor a medicinal chemist, this comes solely from my reading in the disease’s literature.)

      1. Josh B says:

        Azithromycin benefits people whose asthma is triggered by a bronchial infection in two ways – fighting a secondary bacterial infections and as a bronchodilator. It may be that whatever “activity” is seen is due solely to the zithro.

      2. Aaron J Gill says:

        Unless its ciclesonide, that’s expected. Ciclesonide is pretty novel…shows anti-viral activity (Korean PKI), low bioavailability, small molecule prodrug assembles and is effective and concentrated in alveoli… (old information attached) PKI available via google.
        https://www.medscape.com/viewarticle/512158

  35. JB says:

    Any word yet on the cocktail of antibodies developed by Regeneron?

    1. Derek Lowe says:

      Nothing yet – they are a pretty competent bunch over there, though, so I’ll be very interested to see what they come up with.

  36. Lane Simonian says:

    In a strange way, may be it is a good that the Chinese got the first crack at the coronavirus. Very few of the clinical trials that they are running using herbs and other natural products would have been run in the United States (the partial exception being high dose infusions of Vitamin C). The only bad part is that the results may be interpreted via confirmation biases with those who believe the substances will work will over tout the results whereas those who believe they don’t work will highlight the flaws in the trials.

    My own bias is that what the Chinese are trying is at least as likely to succeed as what U.S. (and other western) scientists are trying.

  37. oliver says:

    Hi Derek

    Here is the link to the thorough debunking of the Marseille study by, you guessed it, Leonid Schneider. The comments are fascinating and increasing daily.

    https://forbetterscience.com/2020/03/26/chloroquine-genius-didier-raoult-to-save-the-world-from-covid-19/

    Cheers, Oliver

  38. Brad Wehde says:

    It seems that the efficacy of Hydrogen Peroxide on the Coronavirus is VERY high and there is a method of using a dilute amount of 35% food grade H2O2 with the patient using their own blood in a transfusion method.

    1. Isaac Castaneda says:

      Hello, do you have more information about it? about the use of O2H2 you mention.

      Thanks!
      Isaac

  39. Toni says:

    Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma:
    file:///C:/Users/rober/Downloads/jama_shen_2020_pc_200002.pdf

    CONCLUSIONS AND RELEVANCE In this preliminary uncontrolled case series of 5 critically ill
    patients with COVID-19 and ARDS, administration of convalescent plasma containing
    neutralizing antibody was followed by improvement in their clinical status.
    The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.

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