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Hydroxychloroquine did not lead to faster symptom improvement among patients who had Covid-19 symptoms and were not hospitalized, according to a new study published Thursday in the Annals of Internal Medicine.

The study, a randomized controlled trial led by researchers at the University of Minnesota, adds to the evidence that the malaria drug, heralded as a treatment based on scant data early in the pandemic, has little utility in treating Covid-19. It is likely to add to the smoldering political conflict around the drug, which President Trump said he took to prevent Covid-19 infection. But the study itself has significant limitations that prevent it from being a final word on the subject.


On Tuesday, Peter Navarro, the president’s trade adviser, made his faith in hydroxychloroquine part of a broadside against Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, in USA Today. “[W]hen Fauci was telling the White House Coronavirus Task Force that there was only anecdotal evidence in support of hydroxychloroquine to fight the virus, I confronted him with scientific studies providing evidence of safety and efficacy,” Navarro wrote.

Three high-quality randomized controlled studies, the gold standard in evaluating medicines, have been stopped because hydroxychloroquine was providing no benefit at all for patients. Results from one, the RECOVERY study run by U.K. researchers, were released on a preprint server Wednesday and show that not only was there no statistically significant difference between the arms of the trial, the patients on hydroxychloroquine tended to do worse.

But proponents, including Navarro, have argued that the drug needs to be used earlier in the disease. The Minnesota study represents the first test of using the drug among patients who have not been hospitalized.


The Minnesota study is one of a triad of randomized controlled trials, organized by David Boulware, that aimed to test hydroxychloroquine’s efficacy. One tested giving the drug to people after they were exposed to patients with Covid-19; that trial also failed. This trial tested using the drug right after symptoms began. A third study, for which results have not yet been reported, gave hydroxychloroquine to doctors and other people at high risk of getting Covid-19 before they were exposed to the virus.

To conduct these studies, the researchers made significant compromises. They could not obtain diagnostic testing for all patients, so included people who had symptoms but couldn’t get a test result. In the end, only 58% of the people in this study had diagnostic test results. The researchers mailed study drug or placebo to patients without examining them after they enrolled over the internet, meaning they used data patients self-reported. In the end, the study randomized 491 patients, 432 of whom contributed data to the final analysis.

The patients on hydroxychloroquine recovered 12% faster, or 0.27 points on a 10-point scale, but this difference was far from statistically significant. Patients on hydroxychloroquine also had side effects: 31% had upset stomachs and 21% diarrhea, both about double the rates in the placebo group, though no patients reported cardiac arrhythmias. Overall, adverse effects were reported by 43% of hydroxychloroquine patients and 22% of placebo patients.

The question is, given the study’s limitations, what weight should be given to the results?

“The study was of such low quality that it was fundamentally uninterpretable,” said Steven Nissen, a veteran clinical trialist at the Cleveland Clinic. Still, he said, the evidence against hydroxychloroquine is mounting. “In this study there is no evidence of a benefit for hydroxychloroquine, and it is probably time to move on and start testing other therapies,” he said.

The main problem, Nissen said, is that the evidence on hydroxychloroquine should be coming from large, well-funded studies that were big enough to give clear answers. “Instead of focusing on one or two large, well-powered, well-run rigorous trials, we’ve got a bunch of observational studies, low quality randomized controlled trials, and no answers.”

  • About the RECOVERY trial and why patients did worse on than off HCQ:

    The toxic dose of HCQ is 20mg/kg, lethal 30mg/kg. For a 100 kg person this amounts to 2g resp. 3 g.

    What the RECOVERY trial patients accumulated during the 10 day course is a blood level of HCQ equivalent to 8 g HCQ. Definitely lethal. No wonder less people survived, they were killed by the HCQ overdose.

    If you have Matlab or Octave software you can run the simulation yourself with the unconditionally open source programs on

  • “4 or more hydroxychloroquine doses reduced risk of coronavirus in healthcare workers: ICMR study

    A sustained intake of anti-malarial drug hydroxychloroquine (HCQ) has shown positive results in reducing the risk of coronavirus in the healthcare workers, the ICMR study says.”

    “The ICMR study indicates that “simply initiating HCQ prophylaxis did not reduce the odds of acquiring Covid-19 infection among HCWs. However, with the intake of four or more maintenance doses of HCQ, the protective effect started emerging. A significant reduction of about 80 per cent in the odds of Covid-19 infection in the HCWs was identified with the intake of six or more doses of HCQ prophylaxis. This dose-response relationship added strength to the study outcomes.”
    “Biologically, it appears plausible that HCQ prophylaxis, before the onset of infection, may inhibit the virus from gaining a foothold,” researchers said in the study.”

    “”Of the 172 cases and 193 controls reporting HCQ intake, no significant difference in the occurrence of adverse drug reactions was noted,” the study noted.”

  • The study cited admits its own limitations. Other studies have found that the hydroxy treatment is preventative not a cure for those critically affected. It works on people with low level symptoms, not acute. The article misrepresents the medical application of hydroxy chloroquine and omits the inclusion of Zinc in treatments. Why is the whole regime not fully stated? Because it’s pro big Pharma that hasn’t yet come up with an effective treatment at all! If it did it would be unaffordable any way. The Spanish Flu epidemic was halted by exposing those affected to sunlight. The “Lockdowns” are designed to keep people indoors, out of the sun.

    • Neither of these statements is true. “The Spanish Flu epidemic was halted by exposing those affected to sunlight. The “Lockdowns” are designed to keep people indoors, out of the sun.” What a twisted perspective.

  • There are “elites”/”experts” who think we believe in the lies they write about hydroxychloroquine. It is time to leave the choice of healthcare or medicines to doctors and their patients.

  • Why wasnt this tested on large groups? This drug was dismissed too quickly.
    Diarrhea and stomach upset? That’s a COVID19 symptom! So why would that be a hydroxychloroquine side effect ? So is heart palpitations! So it means nothing that these are listed as side effects because they are all virus related SYMPTOMS
    I know because I had them as symptoms.
    I think it could possibly have been a useful treatment if the CDC AND FDA had let people with Covid and their doctors decide if they wanted it.
    Knowing this drug was out ther and I couldn’t get it infuriates me. I should have been able to make my own decision on taking this drug since no one had a clue about this virus.
    I don’t appreciate the government telling me I can’t have it.

    • It’s pretty obvious that the Minnesota trials are severely compromised. The Henry ford trial was solid and proved that Hydroxychloroquine combo was very effective. Unfortunately it didn’t include zinc. Eventually the truth will prevail. I think most people have already figured out what’s going on.

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