Ranger222 said:

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Every week I come back to this board and I still don't understand why the discussion on hydroxcholorquine is still taking place.

There is not a single well controlled, large sample size study that shows it works.

In fact, more and more research comes in weekly that it is not effective.

https://www.medrxiv.org/content/10.1101/2020.07.20.20157651v1

https://www.nature.com/articles/s41586-020-2575-3

https://www.nature.com/articles/s41586-020-2558-4

At this point, we need to putting our limited resources into something else. We did the science, and it does not work as hoped. Let's move on.

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The discussion is still taking place because there is still a lot to discuss about it and doctors are still prescribing it and describing success with it.

In fact Reveille (wasn't this board started because of his contributions to the discussion of Covid?) said this last night:

Quote:

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Now for the next topic that they brought up with hydroxycholoroquine. Once again we have discussed this many times before. The evidence is now mounting that when used early and with Zinc that is an effective treatment at reducing hospitalizations, intubations, and death.
There are now 65 published studies on use of HCQ with only 16 negative, about 10 inclusive and the rest positive. Here is a link to them all. https://c19study.com/ CNN and MsNBC lead the news with the Lancet and NEJM studies because it fit the narrative to make Trump look bad. They touted that not only did it not work but could harm you. Those studies were found to have fake data but even before that I mentioned here that using HCQ after admission to the hospital is not likely to show benefit as the viral load is way too high and inhibiting viral replication when you already have hundreds of millions of copies is likely futile. In addition when doctors discuss positive studies of HCQ on youtube, facebook etc they are taken down. Since when do we live in a country of censorship? Good chance this gets taken down if someone from facebook reads it.
Now we have many studies showing that early outpatient intervention with HCQ and Zinc can reduce the rate of hospitalization, intubations and death. The one linked below showing hospitalizations were reduced 84%, with only 1 death in treatment group vs 13 in control group. Positive studies like this one are almost never even mentioned on the air. Just like Fox coverage of the masks this is disgraceful and purposely misleads the public for their own agenda not what's best for the people watching.
https://www.preprints.org/manuscript/202007.0025/v1
So I believe these doctors' results? Absolutely I do! I personally have treated close to 100 Covid-19 patients with HCQ/Zinc and either Z-pak or doxycycline. Many republicans and many democrats, but I have yet to have a patient admitted to the hospital. Is it anctedocal? Absolutely! But I have not talked to a single doctor in the community that is not seeing good results. Is it a cure? Absolutely not, that is WAY overstating its effectiveness. But it certainly does appear to be an effective treatment when used early in the disease that reduces your risk of hospitalization.
Isn't that what we are looking for anyway? Do we close the economy for colds? No, because while millions of people get them few get hospitalized and die so no one really cares. Lets focus on reducing Covid-19 to this level.
Still don't believe in HCQ even with all these studies now that simply look at the deaths per millions of countries that are using it all the time. They are significantly lower than those that do not.
As for the safety of HCQ. We have been using this for 65 years and until mentioned by Trump the only safety issue was eye damage with long term use. Patients were required to get annual eye exams. Did we get EKG's on patients needing it to go to Africa or another area with malaria? No we did not, we just prescribed it.
Do I agree with the frontline doctors mentioning it to be over the counter? Not sure I would go that far, but under medical supervision it is an extremely safe medication. Read those studies above or the reviews I did previously and you will see that the side effects are minimal. This QT prolongation has been completely overblown by CNN and MsNBC once again to promote their own agenda. Is it possible certainly, is it common absolutely not. Even more importantly how often is someone suffering an arrhythmia from it. The only studies bearing this out have been voluntarily withdrawn. Unfortunately, this has likely scared many high risk people away from using the medication. Remember, you are only taking it for 5 days and Rheumatoid Arthritis and Lupus patients take them for life. Your risk of a side effect in 5 days is very very low.
So STOP playing politics and start being an American that wants to help save lives and end this pandemic. Together we can control this pandemic but apart we are only making it worse.

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I don't think that additional testing of the veracity of something should be contingent on someone being a proponent or opponent. Testing the veracity of hypotheses and seeing if results can be replicated is just part of the process.

And here we are. Scientific method in sarcastiquotes.

Hypothesis: Hydrocholorquine improves patient outcomes with COVID-19 when administered.

Experiment: Separate patients into two groups, one given HCQ, the other not in a large, randomized control study.

Results:

Quote:

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'A total of 1542 patients were randomised to hydroxychloroquine and compared with 3132 patients randomised to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; p=0.10). There was also no evidence of beneficial effects on hospital stay duration or other outcomes.

'These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19.'

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https://www.recoverytrial.net/news/statement-from-the-chief-investigators-of-the-randomised-evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-from-use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19

This is science and the scientific method. We had a hypothesis, we tested it, the hypothesis is null.

I'm not sure what more we want.

Very early on when we lacked effective treatments, hydoxychloroquine was worth taking a shot in. Now that we have had time to run tests and large trials, we can effectively say it doesn't work. Those are facts.

Based on these results, I would not take hydoxychloroquine today. That is MY choice. I would have in March and April, but after seeing the data, it is clear there is no benefit. You may want to rely on anecdotes from others rather than science. That is YOUR choice. There might be doctors that continue to push the old anecdotes rather than the science. That is THEIR choice. There is enough data today for everyone to make their own choices.

What is clear is we are now wasting time and resources. We don't need any more experiments or trials with hydroxychlorquine. We MUST move on to other potential therapeutics.

A couple points:
1) Hydroxychloroquine was only mentioned as a treatment because it was what part of a South Korean treatment plan. We saw what the South Koreans were doing and copied it because we had no treatment when then pandemic started. We were basically throwing **** at a wall to see if it stuck. Since then we have better practices and treatments for patients in the hospital.
2) There is no clear mechanism of action for hydroxychloroquine, only speculative. Even with combining zinc or whatever else. There is no basic science explanation for how it would work. Four months later there is still no explanation of how it would actually work to provide a benefit to a patient.

Quote:

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'These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19.'

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This is a test of the wrong hypothesis.

Picadillo said:

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https://theplantstrongclub.org/2020/07/17/hydroxychloroquine-the-one-chart-you-need-to-see/

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Look out COVID @gummibear737 made a bar graph

Red Fishing Ag93 said:

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Swing and misses. All of those.

Stay awhile so you can be better informed in the discussion of the topic in this forum.

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The Scientology Strategy

Keegan99 said:

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Quote:

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'These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19.'

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This is a test of the wrong hypothesis.

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So what is the right hypothesis?

Post-exposure prophylaxis? Because we have a couple RCTs now on that.

https://www.nejm.org/doi/full/10.1056/NEJMoa2016638

Quote:

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After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.

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Spanish RCT on PEP that has not published its results but has reported negative results
https://clinicaltrials.gov/ct2/show/NCT04304053

What about treating in early disease? Well, we have an RCT for that too?

https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa1009/5872589

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Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial

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Quote:

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In patients with mild Covid-19, no benefit was observed with HCQ beyond the usual care.

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This will be the point where the conversation will switch back to "but none of those trials used zinc", despite there being no biochemically plausible indication for zinc inclusion given that the original in vitro study did not require zinc to demonstrate its supposed anti-viral replication effects, and obviously HCQ works well as an anti-RA and anti-malarial med without the use of zinc. So why is zinc suddenly so necessary for COVID?

Dr. Not Yet Dr. Ag said:

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Keegan99 said:

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Quote:

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'These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19.'

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This is a test of the wrong hypothesis.

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So what is the right hypothesis?

Post-exposure prophylaxis? Because we have a couple RCTs now on that.

https://www.nejm.org/doi/full/10.1056/NEJMoa2016638

Quote:

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After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.

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Spanish RCT on PEP that has not published its results but has reported negative results
https://clinicaltrials.gov/ct2/show/NCT04304053

What about treating in early disease? Well, we have an RCT for that too?

https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa1009/5872589

Quote:

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Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial

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Quote:

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In patients with mild Covid-19, no benefit was observed with HCQ beyond the usual care.

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......


This will be the point where the conversation will switch back to "but none of those trials used zinc", despite there being no biochemically plausible indication for zinc inclusion given that the original in vitro study did not require zinc to demonstrate its supposed anti-viral replication effects, and obviously HCQ works well as an anti-RA and anti-malarial med without the use of zinc. So why is zinc suddenly so necessary for COVID?

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Here is another RCT out of Brazil on mild-to-moderate disease that was just published by NEJM on 7/23: https://www.nejm.org/doi/full/10.1056/NEJMoa2019014?query=TOC

Quote:

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Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19

BACKGROUND
Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.

METHODS
We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.

RESULTS
A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.

CONCLUSIONS
Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123. opens in new tab.)

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I know I already said this, but I'll say it again. I would encourage y'all to read Dr. Reveille's post from last night. He talks about all 65 studies that have been published so far. 39 have been positive, 10 have been inconclusive, and the others negative and for some reason people just keep talking about the negative ones. He specifically called out the fake data used in the NEJM study that people keep referencing.

JJMt said:

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You guys keep swinging and missing. Show studies that considered the following hypothesis:

HCQ + Zinc + Azithromycin(or Doxycycline - I think) administered immediately after the onset of symptoms.

There are 4 elements critical to the hypothesis. Not one, not two, not three, but four.

All of your studies, at least so far, omit one or more of those critical elements.

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How am I swinging and missing? I haven't made any comment on zinc because I currently don't see any studies that have been released regarding its use in COVID. Are you able to provide any studies that test your hypothesis? If so, please share. On my review, there are multiple clinical trials in the early stages, but I do not see any with released data. I don't call that swinging and missing, I call that evidence-based.

But you see how ridiculous that is, right? What's to stop the next guy in line from saying zinc AND tigers blood? AND waning moon?

There is a proposed method of action for the HCQ and zinc part - it's supposed to act as zinc ionophore. Docs say people who aren't malnourished have plenty of ambient zinc, and the hard part is not getting enough zinc but getting it into the cell. If I'm not mistaken in the in vitro experiment the effect persists with varying levels of ambient zinc. So... I guess the question is why is additional zinc needed? I suspect the answer is: it isn't, and this is just another example of a plausible method of action that works in vitro but fails in practice. It's not the first and won't be the last.

Who you got?

Internet Warriors or Medical Doctors?

chap said:

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I know I already said this, but I'll say it again. I would encourage y'all to read Dr. Reveille's post from last night. He talks about all 65 studies that have been published so far. 39 have been positive, 10 have been inconclusive, and the others negative and for some reason people just keep talking about the negative ones. He specifically called out the fake data used in the NEJM study that people keep referencing.

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I have not referenced the withdrawn NEJM data. The NEJM PEP study is a completely different study. As for his post, unfortunately some physicians are far enough removed from academic medicine to not remember the hierarchy of medical literature, and what constitutes high quality evidence. Not all studies are created equal. Below is a table of how we typically classify level of evidence in medicine. Level C evidence generally leads to weak recommendations, and is usually ignored for physician preference. Level A evidence essentially sets standard of care. What has been posted by myself and others definitively demonstrates level A evidence for lack of efficacy for HCQ for COVID. If you ignored all the negative RCT data, what you would be left with is level C evidence.

Efficacy can only be determined through randomized controlled trials or very well controlled, large patient population prospective cohort studies with a large effect size, anything short of that is low quality evidence and cannot definitively determine efficacy. The reason you keep seeing us only posting negative studies, is because we are only posting high quality evidence, and unfortunately of the available high quality evidence, every single study is negative.

If you actually read those positive observational studies, you will see that all of them call for randomized control trials to determine efficacy (outside of Raoult's)...well those RCTs are being posted for you to peruse.

chap said:

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I know I already said this, but I'll say it again. I would encourage y'all to read Dr. Reveille's post from last night. He talks about all 65 studies that have been published so far. 39 have been positive, 10 have been inconclusive, and the others negative and for some reason people just keep talking about the negative ones. He specifically called out the fake data used in the NEJM study that people keep referencing.

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I read Reveille's post, I don't disagree with him, it is simply another perspective. How he interprets the currently available evidence and how it influences his practice and management of COVID-19 seems to be doing well for him, I don't dispute his words and I am happy to hear he is having positive results. But that doesn't mean how he practices can be extrapolated on a large scale, there are many others factors that need to be controlled in order to make any meaningful conclusion.

Regarding why individuals seem to only be referencing the negative studies, to echo what InfectionAg mentioned earlier, it is because the onus is on those making the affirmative claim. It is scrutiny and discourse, such as what is seen in this thread, that ensures medicine continues to be practiced in an evidence-based manner and is held to a high standard.

Lastly, the simple number of positive, negative, or inconclusive studies on this (or any) matter should not be the sole determinant for what conclusion you make. The gold standard for evaluating this type of question is a controlled, double-blind, randomized clinical trial. On my cursory evaluation of all the published studies on C19study.com since February of this year, only 26 of them were labeled as clinical trials, the majority of which were either not controlled, randomized, and/or blinded; but given the pandemic that is not unexpected and I am not discounting them for not being so (although they still must be taken with a grain of salt). Of those 26, only 13 were labeled as positive in support of the use of hydroxychloroquine in some fashion (be it PrEP, PEP, early use, or late use). So without being able to go into further detail and analyze each study, on a cursory evaluation of the available "quality" data, only half of the clinical trials support the use of hydroxychloroquine in some fashion.

ETA: looks like my ranting got the better of me and Dr Not Yet Dr. Ag was quicker to the punch, but I echo his sentiments

Red Fishing Ag93 said:

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In that very impressive chart, where does the study measure that has all four components of the hypothesis?

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It's not on there, but you already knew that. But to answer your question, here is a clinical trial attempting to answer your hypothesis: Hydroxychloroquine and Zinc With Either Azithromycin or Doxycycline for Treatment of COVID-19 in Outpatient Setting


Whenever they are done recruiting patients and have published results then you will have your answer. Estimated completion is December 2020.