Remember that clinical trial, promoted by President Trump, of a possible COVID-19 cure? So, so, so many questions...
- Reference: 1585361857
- News link: https://www.theregister.co.uk/2020/03/28/coronavirus_hydroxychloroquine_azithromycin/
- Source link:
As world leaders face mounting pressure to contain the novel coronavirus, and hospitals are overwhelmed with patients needing beds and ventilators, there is a desperate search to find a vaccine as well as a cure. Unfortunately, desperation can lead to the grabbing of straws.
Medics and researchers have given some COVID-19 sufferers drugs designed to treat other illnesses to help alleviate their symptoms. Chloroquine and hydroxychloroquine, normally used to treat malaria, and azithromycin, an antibiotic, have been touted as potential treatments although there is little evidence to back it up.
Last week, Trump said he hoped hydroxychloroquine and azithromycin would be “put in use immediately” and cited a paper [1]published in the International Journal of Antimicrobial Agents as evidence of their effectiveness.
HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine. The FDA has moved mountains - Thank You! Hopefully they will BOTH (H works better with A, International Journal of Antimicrobial Agents)..... — Donald J. Trump (@realDonaldTrump) [2]March 21, 2020
Let's take a closer look at that study, led by France's Aix-Marseille University. The clinical trial, which involved just 42 patients who tested positive for COVID-19, was, it is argued, not particularly well designed, with too many variables, potentially throwing the results and its conclusions in doubt. The patients were of different ages, were affected by the illness to different degrees, and treated at different hospitals in France in three groups. Six of the test subjects, one of which died, did not even complete the experiment.
The journal-published study began some time in “early March” and ended on March 16. Out of the 42 patients, six were asymptomatic, 22 had upper respiratory tract infection symptoms, and eight had lower respiratory tract infection symptoms. The patients were as young as ten and as old as 85.
Initially, 26 patients were administered daily doses of 600 milligrams of hydroxychloroquine; six took 600 milligrams of hydroxychloroquine plus azithromycin every day; and the rest acted as a control group and were not fed the cocktail of drugs at all.
All the patients were tested for COVID-19 virus levels with nasal swabs during the 14-day study. The trials were cut short for the aforementioned six who were given hydroxychloroquine only. Three of the six had worsened enough that they required intensive care, one died, one got too sick from the drug, and the other decided to leave hospital. In the end, the hydroxychloroquine group dwindled to just 20 patients instead of the initial 26.
Here’s a graph of the results:
[3]
Graph showing the rate at which patients reduced their coronavirus count after taking, or not taking, hydroxychloroquine and/or azithromycin ... Tap to enlarge (Source: Raoult et al)
All the patients treated with hydroxychloroquine and azithromycin rid themselves of the virus after five days. The recovery rate was slower for those given hydroxychloroquine only, and was worse for the control group.
“Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction [or] disappearance in COVID-19 patients and its effect is reinforced by azithromycin,” the paper concluded.
Was the paper even peer-reviewed?
There are so many questions arising from this study. Was the trial fair? What about the people who got too sick to continue or died? Why do the results only include data from the first week when the trial supposedly lasted 14 days? These queries, and others, were left on [4]PubPeer , a website where academics can discuss papers after peer-review.
Elisabeth Bik, a science consultant and an [5]expert in microbiome research, dug deeper, and found more red flags; not only is the study seemingly flawed, it appears to have been whisked through the peer review process. The paper was accepted on March 17, a day after the study ended, and published online three days later.
It often takes several months for a paper to be accepted and published online, as reviewers and editors work through the contents and suggest edits to the authors. Even allowing for the urgency surrounding the coronavirus pandemic, the paper's rapid turnaround is eyebrow-raising. Bik thought something was up when she discovered one of the co-authors listed on the paper was, in fact, the editor-in-chief of the journal it was published in.
“This would be the equivalent of allowing a student to grade their own paper,” she [6]said . “Low and behold, the student got an A+.”
UK Prime Minister Boris Johnson, health secretary Matt Hancock both test positive for COVID-19 coronavirus [7]READ MORE
Bik told The Register the academics – led by Didier Raoult, a well-known French doctor and microbiologist who is skeptical of human-caused climate change – should have seen the criticism posted on PubPeer by now, and they have yet to respond. “The page dedicated to the [8]preprint of the Raoult paper has been set up to send emails to four of the authors of the study. That post has over 50 comments, so all four authors must have each got 40 emails by now. So far, none of them have responded,” she said.
“This does not mean I am accusing anyone of science misconduct," Bix told El Reg . "But as the senior author and leader of his institute, Raoult is ultimately responsible for the quality and integrity of everything that has his name on it. In scientific publishing, all authors accept that responsibility, and the senior person is responsible for creating an atmosphere of honesty and integrity in their lab."
Given the clinical trial's shortcomings, Bik believes the evidence for hydroxychloroquine and azithromycin as effective drugs to treat COVID-19 is still too thin.
“It is too early to tell, in my opinion," she said. "An additional randomized clinical trial, in which patients who will or will not be treated with hydroxychloroquine and azithromycin should be randomly assigned to either groups, and not handpicked by the study authors, is needed.
“The two groups should be larger than the Raoult study, which should not be hard since there are so many people being infected. There should also be a large trial to study the effectiveness of the drugs as a prophylactic, which has not been proven at all so far, but which is how most people want or believe it to work.”
Raoult, and his co-author and editor-in-chief of the International Journal of Antimicrobial Agents, Jean-Marc Rolain, did not respond to The Register 's request for comment. ®
A husband and wife in Arizona took chloroquine phosphate , an ingredient of fish parasite killers rather than the anti-malaria medication, following the President's recommendation. The man [9]died soon after ingesting the toxic chemical. His spouse was left in a critical condition. "Trump kept saying it was basically pretty much a cure," she later told NBC. “Don’t take anything. Don’t believe anything. Don’t believe anything that the President says and his people ... call your doctor.”
[1] https://www.sciencedirect.com/science/article/pii/S0924857920300996
[2] https://twitter.com/realDonaldTrump/status/1241367239900778501?ref_src=twsrc%5Etfw
[3] https://regmedia.co.uk/2020/03/27/covid_19_trial_study.jpg
[4] https://pubpeer.com/publications/B4044A446F35DF81789F6F20F8E0EE
[5] https://www.linkedin.com/in/elisabeth-bik-4376782/
[6] https://scienceintegritydigest.com/2020/03/24/thoughts-on-the-gautret-et-al-paper-about-hydroxychloroquine-and-azithromycin-treatment-of-covid-19-infections/
[7] https://www.theregister.co.uk/2020/03/27/prime_minister_tests_positive_coronavirus/
[8] https://www.medrxiv.org/content/10.1101/2020.03.16.20037135v1
[9] https://www.nbcnews.com/health/health-news/man-dies-after-ingesting-chloroquine-attempt-prevent-coronavirus-n1167166
I know a couple things about clinical trials.
And if chloroquine was REALLY the cure-all that people keep hoping it is, the current trials would have been ended early with a declaration of victory and a clearance for medical personnel around the world to start using it widely against the coronavirus. Considering that this hasn't happened, it is much more likely that chloroquine is useful for patients at some stages of the disease, but not others, or that it is somewhat useful against coronavirus infection, or it is not that useful at all.
I certainly hope for positive news from the various chloroquine trials going on, but for now, I would not encourage people to go out of their way to get or use the drug.
There was the other bit in the statement....
"The FDA has moved mountains - Thank You!"
The FDA response?
WTF? We haven't approved the drugs for use against Covid19
That's a very diplomatic way of saying "scam"
The most important statement in the whole article.
"Don’t believe anything that the President says..."
Re: The most important statement in the whole article.
Well, he keeps reminding everyone that he is the world's smartest person.... which leads me to reference allegedly by P.T. Barnum about a sucker being born every minute for those following medical advice from Trump.
The most important statement in the whole article.
-And because of that, whatever happened in France *must* be wrong and discarded.
Right after those comments by President Trump, Dr. Fauci mentioned that the reports were "anecdotal". To a prissy statistician bureaucrat , everything is 'anecdotal' if it is not a perfectly designed test structure and report with a control group.
To him, if 10,000 doctors treated 100 patients each, and 96% of them recovered, it would still be 'anecdotal' reports. Unless of course, there were another million patients, who were given nothing, (and of which maybe 50% would have died).
Typical of the LameStreamMedia to latch onto President Trump's reference to the drugs being FDA approved and call that a lie (since the FDA has not approved *anything* to treat the coronavirus). But this is not what the President said, nor meant to imply.
There are two things going on here: alleviating patients and doing research. Doing the first can often, and should often conflict with the second.In a more rational world the power of the FDA to obstruct the first would be much more restricted.
Trump, the *real* Covid 19 victim?
Even doing some reading suggests it suppresses the immune systems response. The sort of thing you'd use only on patients whose immune system is doing more damage than the virus. Other cases it would weaken the patient at a time they need their immune system. FDA does that research, and specifies those cases. Not Trump, not Fox News.
I get it: you think Trump is the real victim here.
You backed him, you cannot face the error of your choice. To admit he's a lying moron, would be to admit you're an idiot who fell for his lies. The more of his lies you've ignored, the more invested in the fictional version of Trump you've become.
To you, Corona Virus is an attack from China on Trump...
...And all the people Trump's incompetence and maliciousness kills, well they are 'soldiers' in the fight against China! People to be lauded for their sacrifice in saving the economy! Fox News telling old Republicans, that their death is necessary, because 'China'! They're supposed to be so stupid they volunteer their own lives, rather than let people stay at home for 2 weeks.
None of that is real. You need mental help.
USA has not done lockdown, you are not wearing face masks, you are not self isolating, you are pretending deaths are 'Flu' deaths, you are not testing, and pretending the reported cases is lower.
Republican governors are blocking quaranteen orders, "this State is not China" they say. Simple quarantine methods are blocked and the disease is spreading in their state among their people. So you may as-well plan for 100% infection rate in months, an overwhelmed healthcare system, millions of deaths.
Failure.
You think you don't need 40k ventilators? You need millions of them, tens of millions, if you don't flatten that curve.
You think you lose only unproductive older people? That the people sacrificed are unneeded overhead? People you won't miss?
Trump isn't the victim, they are.
Echo chamber aside
You know, you can simply google stuff! You don't need to echo The Registers endless sarcasm, or Fox News' "Trump is the real victim of Covid19" drivel.
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The studies relating to Covid 19:
https://en.wikipedia.org/wiki/Hydroxychloroquine
"Hydroxychloroquine is also studied as an experimental treatment for coronavirus disease 2019 (COVID-19).[3] Some are also using it off label for the disease.[32]"
"A randomized controlled trial on 30 patients by Chinese researchers showed that hydroxychloroquine "didn’t shorten the time to SARS-CoV-2 clearance".[33][34] Also, in the study patients were being treated with several other treatments (such as lopinavir/ritonavir or umifenovir) at the same time as the hydroxychloroquine treatment, making it difficult interpret the results.[33]"
"A study of 36 patients in Marseille, France, showed a reduction in viral load, but its methodology was criticized.[35] The patients were not randomized, the analysis excluded three patients in the treatment group who were transferred to an intensive care unit and one who died,[36] and the study was published in a journal whose editor-in-chief is one of the article's authors.[37]"
"In vitro studies in cell cultures demonstrated that hydroxychloroquine was more potent than chloroquine against SARS-CoV-2.[38][39] On 17 March 2020, the AIFA Scientific Technical Commission of the Italian Medicines Agency expressed a favorable opinion on including the off-label use of chloroquine and hydroxychloroquine for the treatment of COVID-19.[40] "
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My Takeaway on the mechanism of action:
Looking at the mechanism of action, it seems to dampen the immune system. I read Covid 19 in the lower lung is so aggressive that the immune system cannot distinguish infected cells from nearby cells and kills everything. I assume, from this mechanism, that its use is to lessen the immune response in that case? Which would be hit or miss, you'd presumably only administer it when the immune response is killing the patient? Otherwise it would make things worse!?
Is there a clinician here who can spell the assume mechanism?
Small trial evidence suggests that Quinone helps if administered early enough. That kind of result is similar to other anti-viral treatments like Tamiflu. If you take it too late, the damage is done already and once you are dead, nothing helps, unless your name is Lazarus.
However, the Quinone works in conjunction with other things, notably Zinc and an antibiotic. Without those two, it does almost nothing. That is why there are all these attention seeking allegations of It Works! It Doesn't Work! The Sky Is Falling! We are All Going to Die! flying around. People are cherry picking results to criticize Trump or whoever else they want to criticize, but in the end they just make themselves look stupid.
In the mean time, the large pharmaceutical companies are ramping up production of Quinone and they probably know what they are doing better than a political journalist with a preconceived agenda.
44 is way too small to have any power in a clinical trial - exactly the reason why large scale trials are needed. In this case - the RECOVERY trial at Oxford University is a prime example of how to do scientific research like this properly.