10 ms·

Hard Data on Remdesivir, and on Hydroxychlorquine

42 points by hprotagonist 6y ago

ehayes 6y ago
> I have no interest in goalpost-moving efforts to say that they didn’t administer zinc or azithromycin Don't really have a dog in this fight, but my understanding is that pro HCQ doctors believe that zinc must be included with HCQ --it's not "moving the goal posts" if doctors aren't arguing that HCQ alone is a cure. However it does sound like moving the goal posts if it HCQ is bad because it is not alone a cure. In a study of 932 patient cases, researchers at New York University Langone Health found that the addition of zinc to hydroxychloroquine and azithromycin was associated with a decrease in mortality in patients who were not admitted to the intensive care unit. [1] [1] https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1 https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v...
- helen___keller 6y ago
  Is there a study of just zinc and/or azithromycin? I wonder if that alone would be associated with decreased mortality
  - peter422 6y ago
    There are studies with azithromycin that show no benefit. As far as I’m aware no published RCTs with HCQ + zinc. But there was further research showing HCQ mechanism doesn’t actually do anything so HCQ studies lost steam because they were a waste of time and effort.
- ColanR 6y ago
  Came here to say this. HCQ is the buzzword we use to refer to the treatment, but it's the combination HCQ with zinc or azithromycin that is actually thought to be useful.
  - dboreham 6y ago
    This sounds like the pharmacology version of "you're not holding it right". Supposedly HCQ works because it is a Zinc Ionophore, facilitating intracellular zinc ion transport. Therefore you need zinc ions to transport. But zinc ions exist in the blood of humans. But some humans might be zinc deficient. But you can draw blood and measure their zinc ion concentration and then provide supplemental zinc. So to end up having done a whole study on HCQ efficacy but NOT covered the bases on "zinc needed" seems unbelievable.
    - ColanR 6y ago
      > So to end up having done a whole study on HCQ efficacy but NOT covered the bases on "zinc needed" seems unbelievable. I'm not sure what you're saying. Are you critiquing the study for not measuring and supplementing zinc in the HCQ cohort?
      - strstr 6y ago
        They are saying that, even if HCQ+zinc is more right, HCQ alone should be an effective treatment (just less effective).
- rsynnott 6y ago
  > Don't really have a dog in this fight, but my understanding is that pro HCQ doctors believe that zinc must be included with HCQ Well, they do now, but that only seemed to emerge after it became clear that Raoult's (zinc-free) protocol didn't work.
stephc_int13 6y ago
This can't be serious. "mortality by Day 29 for these patients was 11.4% with remdesivir therapy as compared to 15.2% with the controls." "HCQ-treated patients did not survive better than those not getting the drug: 27% of them died within 28 days, versus 25% in the standard of care group." Those mortality rates are clearly indicative of a strongly biased test group, even if they call it randomized. The normal mortalit rate for Covid-19 is about 0.5% for the general population, and even if you can discuss that and say that is is closer to 3% in some areas, it is not 15% and not 25%. Those studies are about the effect of remdesivir and HCQ for terminally ill patients.
- tmdg 6y ago
  This is clearly stated in the article: "You can see that these were indeed at-risk patients – the overall mortality rate in the general population for coronavirus infections is nowhere near those rates, and it’s a damn good thing it isn’t. The mean age of the patients was 59 years, 64% male, with 50% of them having hypertension, 45% of them obese, and 30% with Type 2 diabetes. So even though they were characterized as mild-to-moderate on enrollment, this was just the sort of group that you’d worry about as a physician." It is still a valuable study even if it is not a study done on the general population.
- rotexo 6y ago
  From the methods summaries: "We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection." [1] "In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality." [2] These trials are explicitly about treating hospitalized patients, which is of course a group with a higher mortality than the general population. Nobody is saying otherwise. Remdesivir is administered intravenously, so it is unlikely you would try to deliver it to people with mild or asymptomatic infections. The comparison between the drugs in the general population would be very hard to do for that reason. Severe illness due to SARS-CoV-2 is such a huge problem that I'm not sure who would instead investigate a drug specifically for mild cases. [1] https://www.nejm.org/doi/full/10.1056/NEJMoa2007764?query=featured_home https://www.nejm.org/doi/full/10.1056/NEJMoa2007764?query=fe... [2] https://www.nejm.org/doi/full/10.1056/NEJMoa2022926?query=featured_home https://www.nejm.org/doi/full/10.1056/NEJMoa2022926?query=fe...
jeffreyrogers 6y ago
The pro-HCQ people are very clear in saying it needs to be administered early before symptoms are severe and with zinc and azithromycin. When 1/4 of your study population is dying then you are obviously not following the protocol advocated for since you've selected extremely sick people. I'm undecided on whether HCQ is effective or not, but attempting to discredit it with shitty science is a large part of why people don't "believe science".
- peter422 6y ago
  Multiple RCTs have been done where HCQ was given as a post exposure prophylaxis. Didn’t do anything significant in terms of reducing infection. It’s not just about doses or timing. It doesn’t work.
  - jeffreyrogers 6y ago
    I wasn't referring to any of those studies. I was referring to this one, which is obviously poorly designed if it's attempting to test the efficacy of HCQ treatment as it is actually proposed. This being shitty science has no bearing on whether HCQ works on not, but does relate to why people distrust the medical research establishment.
    - peter422 6y ago
      It’s a shitty study because after we all know the results you are post facto complaining that they studied the wrong thing?
      - ColanR 6y ago
        The parameters within which HCQ is thought to work have been clearly stated. If a study is attempting to evaluate HCQ without following those parameters, then the study is badly designed regardless of when it's being discussed.
        peter422 6y ago
chrisco255 6y ago
There are dozens of retrospective studies that shows HCQ does work, at least as well as, if not better than Remdesivir. Here's a list: https://c19study.com/ https://c19study.com/
- peter422 6y ago
  Counting the percentage of “positive” studies, regardless of size, methodology or definition of “positive” to determine the efficacy of a treatment might be the most dubious thing posted in this thread.
  - chrisco255 6y ago
    Maybe, but it's a good collection of studies either way. It's never a good idea to put too much stock in one study.
- dboreham 6y ago
  Amazing. Try clicking through on some of the positive papers and read them. See if they are actually about HCQ efficacy. (Hint, I tried and they are not). Is the site some sort of troll fake project?
  - chrisco255 6y ago
    I did. Here you go: The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients https://link.springer.com/article/10.1007/s11739-020-02505-x https://link.springer.com/article/10.1007/s11739-020-02505-x Early Hydroxychloroquine but not Chloroquine use reduces ICU admission in COVID-19 patients https://www.sciencedirect.com/science/article/pii/S1201971220321755 https://www.sciencedirect.com/science/article/pii/S120197122... The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v1 https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v... Etc etc they also have Remdesivir, Vitamin D, Ivermectin and other studies if you click along the top.
wensheng 6y ago
Ahh, the infamous RECOVERY trial, where they give patient dangerous high dosage(2000mg first 24 hours, 800mg each for next 9 days). Also they probably made the decision to stop the trail after that (now retracted) study[0], lots of trials stopped after that study came out. https://does.hcq.work/ https://does.hcq.work/ [0] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
hristov 6y ago
I apologize for being slightly off topic but there is a Covid study that came out just a couple of days ago that has been criminally ignored by the media. You can read it here: https://investors.chromadex.com/news/news-details/2020/ChromaDex-Announces-Study-Results-Showing-Nutritional-Protocol-Including-Nicotinamide-Riboside-Plus-Standard-of-Care-Reduces-Recovery-Time-in-COVID-19-Patients-by-Nearly-30/default.aspx https://investors.chromadex.com/news/news-details/2020/Chrom... It shows that Nicotinamide-Riboside (sold as TruNiagen) with a couple of common vitamins reduced time to recovery by about 30%. This is about the same result as the much touted remdesivir. But while remdesivir is a very serious and expensive drug with serious side effects that has to be administered in a hospital setting under the oversight of a physician, TruNiagen is sold as an over the counter anti-ageing supplement, costs about $1.30 for a daily dose and there are no known adverse side effects (AFAIK, and according to the label). Of course the two things aren't exclusive, you can take both remdesivir and truniagen. Furthermore, the truniagen study was a phase 2 study with 100 patients with mild to moderate symptoms, while remdesivir has been studied for a lot more patients and more seriously ill patients too. (There was no mortality data on the truniagen study, it seems that everyone survived.) Nevertheless, 100 patients is plenty to make the study statistically significant. And considering how low the cost of actually taking truniagen is, I think this study is really important and really positive news in the fight against covid. Again, it is criminal that the media is ignoring it. Truniagen is made by a small company with negligible advertising budget, while other Covid drugs and vaccines are made by massive pharma companies that regularly spend enormous amounts of money on mass media advertising. So perhaps this has something to do with this.

42 points by hprotagonist 6y ago

> I have no interest in goalpost-moving efforts to say that they didn’t administer zinc or azithromycin Don't really have a dog in this fight, but my understanding is that pro HCQ doctors believe that zinc must be included with HCQ --it's not "moving the goal posts" if doctors aren't arguing that HCQ alone is a cure. However it does sound like moving the goal posts if it HCQ is bad because it is not alone a cure. In a study of 932 patient cases, researchers at New York University Langone Health found that the addition of zinc to hydroxychloroquine and azithromycin was associated with a decrease in mortality in patients who were not admitted to the intensive care unit. [1] [1] https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1 https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v...

helen___keller 6y ago
Is there a study of just zinc and/or azithromycin? I wonder if that alone would be associated with decreased mortality
- peter422 6y ago
  There are studies with azithromycin that show no benefit. As far as I’m aware no published RCTs with HCQ + zinc. But there was further research showing HCQ mechanism doesn’t actually do anything so HCQ studies lost steam because they were a waste of time and effort.
ColanR 6y ago
Came here to say this. HCQ is the buzzword we use to refer to the treatment, but it's the combination HCQ with zinc or azithromycin that is actually thought to be useful.
- dboreham 6y ago
  This sounds like the pharmacology version of "you're not holding it right". Supposedly HCQ works because it is a Zinc Ionophore, facilitating intracellular zinc ion transport. Therefore you need zinc ions to transport. But zinc ions exist in the blood of humans. But some humans might be zinc deficient. But you can draw blood and measure their zinc ion concentration and then provide supplemental zinc. So to end up having done a whole study on HCQ efficacy but NOT covered the bases on "zinc needed" seems unbelievable.
  - ColanR 6y ago
    > So to end up having done a whole study on HCQ efficacy but NOT covered the bases on "zinc needed" seems unbelievable. I'm not sure what you're saying. Are you critiquing the study for not measuring and supplementing zinc in the HCQ cohort?
    - strstr 6y ago
      They are saying that, even if HCQ+zinc is more right, HCQ alone should be an effective treatment (just less effective).
rsynnott 6y ago
> Don't really have a dog in this fight, but my understanding is that pro HCQ doctors believe that zinc must be included with HCQ Well, they do now, but that only seemed to emerge after it became clear that Raoult's (zinc-free) protocol didn't work.

stephc_int13 6y ago

This can't be serious. "mortality by Day 29 for these patients was 11.4% with remdesivir therapy as compared to 15.2% with the controls." "HCQ-treated patients did not survive better than those not getting the drug: 27% of them died within 28 days, versus 25% in the standard of care group." Those mortality rates are clearly indicative of a strongly biased test group, even if they call it randomized. The normal mortalit rate for Covid-19 is about 0.5% for the general population, and even if you can discuss that and say that is is closer to 3% in some areas, it is not 15% and not 25%. Those studies are about the effect of remdesivir and HCQ for terminally ill patients.

tmdg 6y ago
This is clearly stated in the article: "You can see that these were indeed at-risk patients – the overall mortality rate in the general population for coronavirus infections is nowhere near those rates, and it’s a damn good thing it isn’t. The mean age of the patients was 59 years, 64% male, with 50% of them having hypertension, 45% of them obese, and 30% with Type 2 diabetes. So even though they were characterized as mild-to-moderate on enrollment, this was just the sort of group that you’d worry about as a physician." It is still a valuable study even if it is not a study done on the general population.
rotexo 6y ago
From the methods summaries: "We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection." [1] "In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality." [2] These trials are explicitly about treating hospitalized patients, which is of course a group with a higher mortality than the general population. Nobody is saying otherwise. Remdesivir is administered intravenously, so it is unlikely you would try to deliver it to people with mild or asymptomatic infections. The comparison between the drugs in the general population would be very hard to do for that reason. Severe illness due to SARS-CoV-2 is such a huge problem that I'm not sure who would instead investigate a drug specifically for mild cases. [1] https://www.nejm.org/doi/full/10.1056/NEJMoa2007764?query=featured_home https://www.nejm.org/doi/full/10.1056/NEJMoa2007764?query=fe... [2] https://www.nejm.org/doi/full/10.1056/NEJMoa2022926?query=featured_home https://www.nejm.org/doi/full/10.1056/NEJMoa2022926?query=fe...

jeffreyrogers 6y ago

The pro-HCQ people are very clear in saying it needs to be administered early before symptoms are severe and with zinc and azithromycin. When 1/4 of your study population is dying then you are obviously not following the protocol advocated for since you've selected extremely sick people. I'm undecided on whether HCQ is effective or not, but attempting to discredit it with shitty science is a large part of why people don't "believe science".

peter422 6y ago
Multiple RCTs have been done where HCQ was given as a post exposure prophylaxis. Didn’t do anything significant in terms of reducing infection. It’s not just about doses or timing. It doesn’t work.
- jeffreyrogers 6y ago
  I wasn't referring to any of those studies. I was referring to this one, which is obviously poorly designed if it's attempting to test the efficacy of HCQ treatment as it is actually proposed. This being shitty science has no bearing on whether HCQ works on not, but does relate to why people distrust the medical research establishment.
  - peter422 6y ago
    It’s a shitty study because after we all know the results you are post facto complaining that they studied the wrong thing?
    - ColanR 6y ago
      The parameters within which HCQ is thought to work have been clearly stated. If a study is attempting to evaluate HCQ without following those parameters, then the study is badly designed regardless of when it's being discussed.
      - peter422 6y ago

chrisco255 6y ago

There are dozens of retrospective studies that shows HCQ does work, at least as well as, if not better than Remdesivir. Here's a list: https://c19study.com/ https://c19study.com/

peter422 6y ago
Counting the percentage of “positive” studies, regardless of size, methodology or definition of “positive” to determine the efficacy of a treatment might be the most dubious thing posted in this thread.
- chrisco255 6y ago
  Maybe, but it's a good collection of studies either way. It's never a good idea to put too much stock in one study.
dboreham 6y ago
Amazing. Try clicking through on some of the positive papers and read them. See if they are actually about HCQ efficacy. (Hint, I tried and they are not). Is the site some sort of troll fake project?
- chrisco255 6y ago
  I did. Here you go: The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients https://link.springer.com/article/10.1007/s11739-020-02505-x https://link.springer.com/article/10.1007/s11739-020-02505-x Early Hydroxychloroquine but not Chloroquine use reduces ICU admission in COVID-19 patients https://www.sciencedirect.com/science/article/pii/S1201971220321755 https://www.sciencedirect.com/science/article/pii/S120197122... The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v1 https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v... Etc etc they also have Remdesivir, Vitamin D, Ivermectin and other studies if you click along the top.

wensheng 6y ago

Ahh, the infamous RECOVERY trial, where they give patient dangerous high dosage(2000mg first 24 hours, 800mg each for next 9 days). Also they probably made the decision to stop the trail after that (now retracted) study[0], lots of trials stopped after that study came out. https://does.hcq.work/ https://does.hcq.work/ [0] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

hristov 6y ago

I apologize for being slightly off topic but there is a Covid study that came out just a couple of days ago that has been criminally ignored by the media. You can read it here: https://investors.chromadex.com/news/news-details/2020/ChromaDex-Announces-Study-Results-Showing-Nutritional-Protocol-Including-Nicotinamide-Riboside-Plus-Standard-of-Care-Reduces-Recovery-Time-in-COVID-19-Patients-by-Nearly-30/default.aspx https://investors.chromadex.com/news/news-details/2020/Chrom... It shows that Nicotinamide-Riboside (sold as TruNiagen) with a couple of common vitamins reduced time to recovery by about 30%. This is about the same result as the much touted remdesivir. But while remdesivir is a very serious and expensive drug with serious side effects that has to be administered in a hospital setting under the oversight of a physician, TruNiagen is sold as an over the counter anti-ageing supplement, costs about $1.30 for a daily dose and there are no known adverse side effects (AFAIK, and according to the label). Of course the two things aren't exclusive, you can take both remdesivir and truniagen. Furthermore, the truniagen study was a phase 2 study with 100 patients with mild to moderate symptoms, while remdesivir has been studied for a lot more patients and more seriously ill patients too. (There was no mortality data on the truniagen study, it seems that everyone survived.) Nevertheless, 100 patients is plenty to make the study statistically significant. And considering how low the cost of actually taking truniagen is, I think this study is really important and really positive news in the fight against covid. Again, it is criminal that the media is ignoring it. Truniagen is made by a small company with negligible advertising budget, while other Covid drugs and vaccines are made by massive pharma companies that regularly spend enormous amounts of money on mass media advertising. So perhaps this has something to do with this.