> Today, three of the authors of the paper, "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis", have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they "can no longer vouch for the veracity of the primary data sources."
From the paper: "Interpretation: We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19."
It's important to keep in mind the study's limitations section, too:
"Our study has several limitations. The association of decreased survival with hydroxychloroquine or chloro-quine treatment regimens should be interpreted cautiously. Due to the observational study design, we cannot exclude the possibility of unmeasured con-founding factors, although we have reassuringly noted consistency between the primary analysis and the propensity score matched analyses. Nevertheless, a cause-and-effect relationship between drug therapy and survival should not be inferred. These data do not apply to the use of any treatment regimen used in the ambulatory, out-of-hospital setting. Randomised clinical trials will be required before any conclusion can be reached regarding benefit or harm of these agents in COVID-19 patients. We also note that although we evaluated the relationship of the drug treatment regimens with the occurrence of ventricular arrhyth-mias, we did not measure QT intervals, nor did we stratify the arrhythmia pattern (such as torsade de pointes). We also did not establish if the association of increased risk of in-hospital death with use of the drug regimens is linked directly to their cardiovascular risk, nor did we conduct a drug dose-response analysis of the observed risks. Even if these limitations suggest a conservative interpretation of the findings, we believe that the absence of any observed benefit could still represent a reasonable explanation.In summary, this multinational, observational, real-world study of patients with COVID-19 requiring hospitalisation found that the use of a regimen con-taining hydroxychloroquine or chloroquine (with or without a macrolide) was associated with no evidence of benefit, but instead was associated with an increase in the risk of ventricular arrhythmias and a greater hazard for in-hospital death with COVID-19. These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed."
Has anyone seen good randomized clinical trials yet?
Does anyone know if zinc a macrolide? All the data I have seen on successful use of hydroxycholoroquine required the use of zinc along side. Also chloroquine is the drug that causes heart issues not hydroxychloroquine. The two are different. If zinc is not a `macrolide` I wouldn’t give this paper much credit as they didn’t test the treatment properly.
Edit: Wow, how the HN community has fallen. Downvoting a simple, honest question into oblivion.
Hydroxychloroquine is a zinc ionophore. It provides an ion channel that permits zinc to enter the cell and inhibit viral replication. In order to be effective, the zinc + ionophore antiviral should be administered early. Hospitalized ICU patients on ventilators are far from ideal candidates. Chinese (successful) studies used Zinc and Hydroxychloroquine; never Hydroxychloroquine without zinc.
Improving the efficacy of Chloroquine and Hydroxychloroquine against SARS-CoV-2 may require Zinc additives - A better synergy for future COVID-19 clinical trials
https://digitalcommons.mtu.edu/michigantech-p/1795/
Wasnt Zinc supposed to be part of the equation along with Hydroxychloroquine?
Most anecdotal evidence from practitioners includes Zinc along with Hydroxychloroquine.
The most impressive one I saw included zinc, but I thought that was unusual. Most do not AFAICT. In fact, zinc may be the beneficial part of that treatment. Any studies on zinc?
Yes, zinc is a key part of the proposed prophylactic regimen. Anyone who thought HCQ by itself would be helpful as a ‘cure’ for those who already are suffering an infection misunderstood the original proposal and care more about politics than accuracy. (i.e. Mr. Trump)
Zinc is the purported mechanism of action, but cells can't pick up enough on their own, so an ionophore like hydroxychloroquine might help get more into the cell.
One might ask pointed questions why the original formulation (zinc + ionophore) is so consistently absent from these studies. I don't care one way or the other about the drug, but why are studies widely promoted that are irrelevant to the question?
I'd easily bet he was never taking it - easier instead to just say he was taking it, say "Look, I'm not sick!", instead of having to admit he was wrong.
The study say nothing on what stade of infection the treatment was applied. The HCQ + AZT treatment was shown effective on initial infection stages, before heavy symptoms appears.
tl;dr: “ There was no evidence whatsoever of any benefit with any of these treatment regimes. There was significant evidence of harm. ... Tell me again why anyone should be advocating such treatments. But your reasons had better stand up to 14,888 patients versus 81,144 comparators. Make it good.“
I’m convinced the only reason this is being advocated by laypeople is to provide false reassurance to vulnerable populations that an effective treatment is available.
Written by who? Reviewed by who else for correctness and (just as importantly) completeness? Paid for by who, with what potential conflicts of interest?
For something purporting to be the current consensus of evidence-based medicine, it sure lacks the usual hallmarks of scientific inquiry: openness, transparency, review.
Edited to add: Plus, that anonymous Google doc doesn't even represent the latest research, because the Raoult paper (under the heading "12 April 2020") has already been retracted:
[+] [-] ghastmaster|5 years ago|reply
https://www.thelancet.com/lancet/article/s0140673620313246
> Today, three of the authors of the paper, "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis", have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they "can no longer vouch for the veracity of the primary data sources."
[+] [-] mhandley|5 years ago|reply
[+] [-] Natsu|5 years ago|reply
"Our study has several limitations. The association of decreased survival with hydroxychloroquine or chloro-quine treatment regimens should be interpreted cautiously. Due to the observational study design, we cannot exclude the possibility of unmeasured con-founding factors, although we have reassuringly noted consistency between the primary analysis and the propensity score matched analyses. Nevertheless, a cause-and-effect relationship between drug therapy and survival should not be inferred. These data do not apply to the use of any treatment regimen used in the ambulatory, out-of-hospital setting. Randomised clinical trials will be required before any conclusion can be reached regarding benefit or harm of these agents in COVID-19 patients. We also note that although we evaluated the relationship of the drug treatment regimens with the occurrence of ventricular arrhyth-mias, we did not measure QT intervals, nor did we stratify the arrhythmia pattern (such as torsade de pointes). We also did not establish if the association of increased risk of in-hospital death with use of the drug regimens is linked directly to their cardiovascular risk, nor did we conduct a drug dose-response analysis of the observed risks. Even if these limitations suggest a conservative interpretation of the findings, we believe that the absence of any observed benefit could still represent a reasonable explanation.In summary, this multinational, observational, real-world study of patients with COVID-19 requiring hospitalisation found that the use of a regimen con-taining hydroxychloroquine or chloroquine (with or without a macrolide) was associated with no evidence of benefit, but instead was associated with an increase in the risk of ventricular arrhythmias and a greater hazard for in-hospital death with COVID-19. These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed."
Has anyone seen good randomized clinical trials yet?
[+] [-] huy-nguyen|5 years ago|reply
[+] [-] macinjosh|5 years ago|reply
Edit: Wow, how the HN community has fallen. Downvoting a simple, honest question into oblivion.
[+] [-] throwablePie|5 years ago|reply
Improving the efficacy of Chloroquine and Hydroxychloroquine against SARS-CoV-2 may require Zinc additives - A better synergy for future COVID-19 clinical trials https://digitalcommons.mtu.edu/michigantech-p/1795/
Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973827/
Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine/Hydroxychloroquine to Win Todays Battle Against COVID-19? https://www.preprints.org/manuscript/202004.0124/v1]
https://en.wikipedia.org/wiki/Ionophore Zinc ionophores have been shown to inhibit replication of various viruses in vitro:
Coxsackievirus
Equine viral arteritis
Hepatitis C virus
Herpes simplex virus
Human coronavirus
Human Immunodeficiency Virus
Mengovirus
MERS coronavirus
Rhinovirus
SARS coronavirus
Zika virus
[+] [-] maaand|5 years ago|reply
[+] [-] matthewtoast|5 years ago|reply
[+] [-] michaelmrose|5 years ago|reply
[+] [-] Natsu|5 years ago|reply
[+] [-] phkahler|5 years ago|reply
[+] [-] macinjosh|5 years ago|reply
[+] [-] jeremyw|5 years ago|reply
One might ask pointed questions why the original formulation (zinc + ionophore) is so consistently absent from these studies. I don't care one way or the other about the drug, but why are studies widely promoted that are irrelevant to the question?
[+] [-] dispose3141|5 years ago|reply
[+] [-] hn_throwaway_99|5 years ago|reply
[+] [-] faitswulff|5 years ago|reply
[+] [-] unknown|5 years ago|reply
[deleted]
[+] [-] vadiml|5 years ago|reply
[+] [-] unknown|5 years ago|reply
[deleted]
[+] [-] hprotagonist|5 years ago|reply
https://blogs.sciencemag.org/pipeline/archives/2020/05/22/hy...
[+] [-] rsynnott|5 years ago|reply
[+] [-] jakeogh|5 years ago|reply
[+] [-] xenophonf|5 years ago|reply
For something purporting to be the current consensus of evidence-based medicine, it sure lacks the usual hallmarks of scientific inquiry: openness, transparency, review.
Edited to add: Plus, that anonymous Google doc doesn't even represent the latest research, because the Raoult paper (under the heading "12 April 2020") has already been retracted:
https://retractionwatch.com/2020/05/21/french-hydroxychloroq...