Chloroquine and Hydroxychloroquine as treatments for Covid-19

[Barry]

The two treatment harms do not match, so nothing can be deduced from this study.

Presumably you meant 'arms' .

 

[Cheshire]

Presumably you meant 'arms' .

Oh yes, sorry, I will change it.

 

[Barry]

As I think I pointed out earlier, because chloroquine has a long half life

I understand the concept of half life and exponential decay, but could you explain (without getting too medically technical) how it relates to medication please.

And I'm guessing that when you talk about a loading dose this is like when I've had to go on emergency doses of antibiotics, a double first dose is typically recommended. Presumably to get a faster ramp up of medicine level within the body.

 

[Barry]

The two treatment arms do not match, so nothing can be deduced from this study.

The HCQ group includes 36.5% of 45-64 years old, but only 23.5% of +80 years. The group without HCQ: 44.6% over 80 years.
The high number of people over 80, with a higher risk of death, could in itself explain why the non treatment group had worst outcomes.

The median ages of the two arms also reflect this, 66 vs 77.

Surely this is so basic they must have attempted some kind of correction for this, even if also potentially flawed? Feels like kindergarten science.

 

[Cheshire]

Surely this is so basic they must have attempted some kind of correction for this, even if also potentially flawed?

Apparently, they haven't...

 

[Jonathan Edwards]

I understand the concept of half life and exponential decay, but could you explain (without getting too medically technical) how it relates to medication please.

And I'm guessing that when you talk about a loading dose this is like when I've had to go on emergency doses of antibiotics, a double first dose is typically recommended. Presumably to get a faster ramp up of medicine level within the body.

If the therapeutic dose of a drug is 100mg in the body and the half life is a day then if you give 100mg a day the level just before taking the next dose is right (1/2 + 1/4 + 1/8 + 1/16... =1). But if the half life is 2 days you will end up with twice as much on board. You want to take 100mg every two days or 50mg a day. If the half life is 7 weeks, as for chloroquine, you want to take 2mg a day. But if you take 2mg a day you will not have an effective level for 7 weeks, which is not much good for treating an emergency.

 

[Keela Too]

Half life basically means the time it takes for half of the substance to decay.

So if half life is 1 day and you start on a single dose of 100 units then
Day 1 = 100
Day 2 = 50
Day 3 = 25
Day 4 = 12.5. Etc

If you then start taking 100 every day the amount will accumulate over time, so Day 2 = 150 etc

So care would need to be taken with the daily dose in order to have the desired amount in the bloodstream over time.

See Jonathan’s post above

 

[Barry]

Yes, so in the same way the dose decays exponentially, there will also be an equivalent exponential approach toward the target quiescent level. Which is why - I'm guessing - when you need antibiotics pretty urgently they give you them intravenously ... presumably the half life is drastically reduced in terms of ramp up.

Is intravenous administration of chloroquine not viable?

 

[Jonathan Edwards]

Yes, so in the same way the dose decays exponentially, there will also be an equivalent exponential approach toward the target quiescent level. Which is why - I'm guessing - when you need antibiotics pretty urgently they give you them intravenously ... presumably the half life is drastically reduced in terms of ramp up.

Is intravenous administration of chloroquine not viable?

The dynamics of getting drug in are a bit different. But IV is certainly given to bypass delay in absorption. Chloroquine may not have an available IV formulation on the shelf known to be safe but it may do (for falciparum malaria?). The delay in absorption is normally only about half an hour from the stomach (if empty) so it is probably not a big issue. IV antibiotics are given because bacterial infection can become critically lethal within maybe an hour or so and vomiting or diarrhoea may lose all the drug. Viruses aren't quite like that.

 

[cassava7]

A very rigorous systematic review from French researchers on the use of HCQ and HCQ+AZT for the treatment of COVID19.

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30505-X/fulltext

"Hydroxychloroquine was not significantly associated with mortality: pooled Relative Risk RR=0.83 (95% CI: 0.65-1.06, n=17 studies) for all studies and RR=1.09 (95% CI: 0.97-1.24, n=3 studies) for RCTs. Hydroxychloroquine with azithromycin was associated with an increased mortality: RR=1.27 (95% CI: 1.04-1.54, n=7 studies). We found similar results with a Bayesian meta-analysis."

Abstract:

Background
Hydroxychloroquine or chloroquine with or without azithromycin have been widely promoted to treat COVID-19 following early in vitro antiviral effects against SARS-CoV-2

Objective
The aim of this systematic review and meta-analysis was to assess whether chloroquine or hydroxychloroquine with or without azithromycin decreased COVID-19 mortality compared to the standard of care.

Data sources
Pubmed, Web of Science, Embase Cochrane Library, Google Scholar and MedRxiv were searched until 25 July 2020.

Study eligibility criteria
We included published and unpublished studies comparing the mortality rate between patients treated with chloroquine or hydroxychloroquine with or without azithromycin and patients managed with standard of care.

Participants
Patients ≥18 years old with confirmed COVID-19.

Interventions
Chloroquine or hydroxychloroquine with or without azithromycin.

Methods
Effect sizes were pooled using a random-effects model. Multiple subgroup analyses were conducted to assess the drug safety.

Results
The initial search yielded 839 articles, of which 29 articles met our inclusion criteria. All studies except one were conducted on hospitalized patients and evaluated the effects of hydroxychloroquine with or without azithromycin. Among the 29 articles, 3 were randomized controlled trials (RCT), one was a non-randomized trial and 25 were observational studies, including 10 with a critical risk of bias and 15 with a serious or moderate risk of bias. After excluding studies with critical risk of bias, the meta-analysis included 11,932 participants for the hydroxychloroquine group, 8,081 for the hydroxychloroquine with azithromycin group and 12,930 for the control group. Hydroxychloroquine was not significantly associated with mortality: pooled Relative Risk RR=0.83 (95% CI: 0.65-1.06, n=17 studies) for all studies and RR=1.09 (95% CI: 0.97-1.24, n=3 studies) for RCTs. Hydroxychloroquine with azithromycin was associated with an increased mortality: RR=1.27 (95% CI: 1.04-1.54, n=7 studies). We found similar results with a Bayesian meta-analysis.

Conclusion
Hydroxychloroquine alone was not associated with reduced mortality in hospitalized COVID-19 patients but the combination of hydroxychloroquine and azithromycin significantly increased mortality.

The authors are 6 young researchers who teamed up via social media. They're now receiving ad hominem (not scientific) criticism from pro-HCQ French MDs, as well as insults & threats from HCQ "supporters". So are journalists who have reported on their review.

Insults and threats for conducting rigorous research. Politics stepping over science. This is beyond horrible.

 

[Cheshire]

The authors are 6 young researchers who teamed up via social media. They're now receiving ad hominem (not scientific) criticism from pro-HCQ French MDs, as well as insults & threats from HCQ "supporters". So are journalists who have reported on their review.

Insults and threats for conducting rigorous research. Politics stepping over science. This is beyond horrible.

Yes, the situation in France is beyond the pale. I just read on one of the authors twitter account how harrassed he has been, is address shared on social media, threats...
The pro-HCQ are acting like a cult/mafia.

 

[TrixieStix]

The two treatment arms do not match, so nothing can be deduced from this study.

The HCQ group includes 36.5% of 45-64 years old, but only 23.5% of +80 years. The group without HCQ: 44.6% over 80 years.
The high number of people over 80, with a higher risk of death, could in itself explain why the non treatment group had worst outcomes.

View attachment 11847

A user on YouTube has sent me this reply when I pointed out that the non-HCQ group was not age matched to the HCQ group. Here is what they said....

"The study controls for other variables which are statistically ruled out. HCQ works independent of the other variables. That is the whole point of an observational study. Big numbers make that easier to do and makes the results more reliable."

Is there any way this could be true? Seems bunk to me.

 

[Jonathan Edwards]

A user on YouTube has sent me this reply when I pointed out that the non-HCQ group was not age matched to the HCQ group. Here is what they said....

"The study controls for other variables which are statistically ruled out. HCQ works independent of the other variables. That is the whole point of an observational study. Big numbers make that easier to do and makes the results more reliable."

Is there any way this could be true? Seems bunk to me.

It certainly seems garbled. None of the arguments follow.

 

[Cheshire]

I'm not sure this answer your question (and sorry, this is in French, if you do'nt read it, the automatic translation is not as bad as it used to be) (the whole thread is about this study)

 

[Barry]

A user on YouTube has sent me this reply when I pointed out that the non-HCQ group was not age matched to the HCQ group. Here is what they said....

"The study controls for other variables which are statistically ruled out. HCQ works independent of the other variables. That is the whole point of an observational study. Big numbers make that easier to do and makes the results more reliable."

Is there any way this could be true? Seems bunk to me.

The issue is not about the "other variables" surely, and so whether HCQ works independently of them has no relevance to the question posed ... even if that statement of theirs has any credibility anyway.

The issue is about the age variables, which have not been controlled for. So I think the evasive response acknowledges it's a 'fail'.

 

[TrixieStix]

thanks for the link to the twitter thread. This part is illuminating.....

"One of the authors of this study (Philippe Gautret) is part of the editorial committee of the journal that accepted this publication. Without being a unique situation in the academic world, it seems to be a well-established tradition in this team." (-David Hajage)

 

[Andy]

Controversial COVID study that promoted unproven treatment retracted after four-year saga

A study that stoked enthusiasm for the now-disproven idea that a cheap malaria drug can treat COVID-19 has been retracted — more than four-and-a-half years after it was published1.

Researchers had critiqued the controversial paper many times, raising concerns about its data quality and an unclear ethics-approval process. Its eventual withdrawal, on the grounds of concerns over ethical approval and doubts about the conduct of the research, marks the 28th retraction for co-author Didier Raoult, a French microbiologist, formerly at Marseille’s Hospital-University Institute Mediterranean Infection (IHU), who shot to global prominence in the pandemic. French investigations found that he and the IHU had violated ethics-approval protocols in numerous studies, and Raoult has now retired.

https://www.nature.com/articles/d41586-024-04014-9