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Medicine

Largest Study To Date Finds Hydroxychloroquine Doesn't Help Coronavirus Patients (time.com) 236

A new hydroxychloroquine study -- "the largest to date" -- was published Thursday in the prestigious New England Journal of Medicine. It concluded that Covid-19 patients taking the drug "do not fare better than those not receiving the drug," reports Time: Dr. Neil Schluger, chief of the division of pulmonary, allergy and critical care medicine at Columbia, and his team studied more than 1,300 patients admitted to New York-Presbyterian Hospital-Columbia University Irving Medical Center for COVID-19. Some received hydroxychloroquine on an off-label basis, a practice that allows doctors to prescribe a drug that has been approved for one disease to treat another — in this case, COVID-19. About 60% of the patients received hydroxychloroquine for about five days.

They did not show any lower rate of needing ventilators or a lower risk of dying during the study period compared to people not getting the drug.

"We don't think at this point, given the totality of evidence, that it is reasonable to routinely give this drug to patients," says Schluger. "We don't see the rationale for doing that." While the study did not randomly assign people to receive the drug or placebo and compare their outcomes, the large number of patients involved suggests the findings are solid. Based on the results, Schluger says doctors at his hospital have already changed their advice about using hydroxychloroquine to treat COVID-19. "Our guidance early on had suggested giving hydroxychloroquine to hospitalized patients, and we updated that guidance to remove that suggestion," he says.

In another study conducted at U.S. veterans hospitals where severely ill patients were given hydroxychloroquine, "the drug was found to be of no use against the disease and potentially harmful when given in high doses," reports the Chicago Tribune.

They also report that to firmly establish whether the drug has any effect, the Bill and Melinda Gates Foundation is now funding a randomized, controlled trial at six medical institutions of hundreds of people who've tested positive for Covid-19.
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Largest Study To Date Finds Hydroxychloroquine Doesn't Help Coronavirus Patients

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  • Shouldn't they be pursuing more promising trial treatments than wasting time and perhaps lives on something useless?

    • Anecdotal (Score:5, Insightful)

      by JBMcB ( 73720 ) on Saturday May 09, 2020 @11:40AM (#60040668)

      There is anecdotal evidence that it helps. There is anecdotal evidence that isn't helpful. There is anecdotal evidence that it is harmful.

      To figure out what it actually does, you need a proper, controlled trial, which is what they are doing.

      • by gweihir ( 88907 )

        Well, there is actually pretty good evidence that id does not help, but the residual error is still to large to completely discount it. Hence they are making sure now. Also, there was a study that recently showed that it does not seem to harm (except in large doses), hence there is no ethical problem with doing a proper double-blind study.

        • by sycodon ( 149926 )

          Here is pretty good evidence that it does help [sciencedirect.com]

          A retrospective analysis of 1061 cases in Marseille, France fond that administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with very low fatality rate in patients. Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%).

          Like other anti-virals such as Tamiflu, you need to begin the treatment early. Waiting until yor patient is almost dead results in dead patients.

          WTF is with p

      • Re:Anecdotal (Score:4, Informative)

        by Anonymous Coward on Saturday May 09, 2020 @12:14PM (#60040788)

        There is anecdotal evidence that it is harmful.

        No, there's already clinical evidence that it can be fatal. Not the same.

      • Re: (Score:2, Interesting)

        by thule ( 9041 )
        Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients: https://www.medrxiv.org/conten... [medrxiv.org]

        From what I've read, the drug doesn't do much by itself. This paper seems to support the idea that it must be combined with something else.
        • Re:Anecdotal (Score:4, Interesting)

          by dgatwood ( 11270 ) on Saturday May 09, 2020 @01:35PM (#60041176) Homepage Journal

          From what I've read, the drug doesn't do much by itself. This paper seems to support the idea that it must be combined with something else.

          Say you have three studies that show:

          A by itself: no effect.
          A + B: no effect.
          A + B + C: significant improvement.

          The rational assumption is "C saves lives", not that "A saves lives, but only in conjunction with B and C."

          What the paper strongly suggests is that zinc sulfate reduces the severity and duration of viral infections [nih.gov], which I think everybody but the die-hard pharmaceuticals-only doctors already knew. Going from there to the assumption that it is more effective in combination with hydroxychloroquine is not supported by any evidence at all. It might be true, but it is approximately equally likely that carrots + peas + zinc sulfate has a better cure rate than zinc sulfate by itself. Just saying.

          IMO, every bit of effort spent experimenting with chloroquine is effort that could be spent experimenting with something that might actually help. About the best that could be said, or so we thought, was that it wouldn't kill anybody. Now that even that assumption has been cast into doubt, the ethical thing to do is to study zinc sulfate by itself and see if there's a similar improvement, and if so, abandon all chloroquine experimentation outright. Don't even bother with a double-blind to confirm that it is useless; if the numbers from the experiments are even within a few percent, walk away.

          • Re: Anecdotal (Score:2, Insightful)

            by Lanthanide ( 4982283 )

            Or perhaps experts in the field know how these chemicals work by themselves and so can form a logical and plausible explanation for why they would be more effective together, which is why they tested that combination and not just component C by itself.

            • by dgatwood ( 11270 )

              Sadly, no. This has basically become political at this point, with hordes of researchers doing studies in an effort to help the POTUS save face.

              There is a small possibility that they might be more effective together, but either way, at this point it should be clear that any experiment lacking a baseline zinc-sulfate-only arm is defective by design.

        • Re: (Score:2, Interesting)

          by barakn ( 641218 )

          This paper is crap. Not only is it not randomized, not blind nor double-blind, but their two groups of people were separated in time. That's right, after a certain point in time everybody started getting zinc sulfate. So we could attribute any improved outcome to the medical staff simply learning how to handle Covid-19 patients better, or to a change in the prevalent strain of the virus. There's so many confounding variables here I could hit one with a dart blindfolded (not sure why the dart wanted to b

      • Re:Anecdotal (Score:5, Insightful)

        by kot-begemot-uk ( 6104030 ) on Saturday May 09, 2020 @12:33PM (#60040864) Homepage

        There is anecdotal evidence that it helps. There is anecdotal evidence that isn't helpful. There is anecdotal evidence that it is harmful.

        To figure out what it actually does, you need a proper, controlled trial, which is what they are doing.

        Ahem. And it should be done. If not for any other reason, the Orange baboon shutting up is a valid enough reason to start off with.

        A few minor corrections:

        1. It has been shown to be effective in vitro at the concentrations which are reached in blood plasma in standard dosages by multiple teams from different countries - Australia, China, Russia (off the top of my head).

        2. This is closer to the French study (by the scandalous Dr Rault) because it started the treatment EARLIER than the veterans one. It is still NOT at the same time as in Dr Rault study because USA admits patients LATER than the admissions in his clinic. His admissions were early on (first signs that temperature refuses to drop). USA, UK, etc admissions are generally "when the sh*t hits the fan" and when the patient has the first signs of breathing difficulties. Any expectations that something with antiviral properties will work at all at that point in time are misplaced. The horse has already bolted. Last, but not least, due to different admission criteria the various studies are not comparable.

      • Re: (Score:2, Informative)

        by gosso920 ( 6330142 )

        There is anecdotal evidence that it helps. There is anecdotal evidence that isn't helpful. There is anecdotal evidence that it is harmful.

        To figure out what it actually does, you need a proper, controlled trial, which is what they are doing.

        Hydroxychloroquine was approved for medical use in the United States in 1955.[2] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[7] In 2017, it was the 128th most commonly prescribed medication in the United States, with more than five million prescriptions.[8][9]

    • To fight the spread of misinformation and the harm caused by it.
    • by quonset ( 4839537 ) on Saturday May 09, 2020 @11:51AM (#60040708)

      The Gates Foundation is not doing anything other than funding a study [geekwire.com] to see if this medicine does anything. That is literally one of the things the foundation is set up for: to study what if.

      It is certain the foundation is looking into other treatments, both ones in development and ones which don't yet exist.

      Perhaps you should be asking why the con continues to push this worthless drug instead of focusing on more promising trial treatments while people are dying, 78,000+ and counting.

      Done trolling yet?

      • by SpankiMonki ( 3493987 ) on Saturday May 09, 2020 @12:02PM (#60040748)

        Perhaps you should be asking why the con continues to push this worthless drug instead of focusing on more promising trial treatments while people are dying, 78,000+ and counting.

        Trump hasn't promoted HCQ for some time now. He's currently promoting Clorox. Try to keep up.

        • by iggymanz ( 596061 ) on Saturday May 09, 2020 @12:05PM (#60040766)

          I find Chlorox with lemon fresh scent to have good nose but rather bitter aftertaste. Perhaps the Head Cheetoh could share his cocktail recipes, maybe I'm just lacking a good mixer or complimentary spirit. I'm thinking Bombay Sapphire would give a cool blue sheen and some botanicals to support the lemony scent.

          • Re: (Score:2, Funny)

            by iggymanz ( 596061 )

            This therapy should of course be supported by a robust daily regimen of lung sunburn. Rather than the weak florescent tubes currently peddled that only give a mild amount of vitamin D in a long period of time, the good old fashioned 400 volt mercury vapor lamps that can sunburn skin in less than ten minutes should be guided into all the major bronchial tubes and left to linger until a pleasant searing sensation is felt.

          • by ath1901 ( 1570281 ) on Saturday May 09, 2020 @01:19PM (#60041098)

            You're doing it wrong. It must do a tremendous number on the lungs so you should try vaping it.

            The Germans were the first to realise this as early in 1915. They managed to delay the outbreak of the spanish flu for three years by freely distributing chlorine gas among british and french troops. The brits and french were so thankful they later reciprocated in kind. Mass distribution of gas was later banned by the UN after intense lobbying from Big Pharma since it was such a cheap, patent-free and effective way of preventing people from dying from the flu.

            It is an established fact that if you inhale large enough amounts of chlorine gas you will NOT die from the spanish flu, covid19, infection, car accidents or even old age.

        • Comment removed based on user account deletion
      • Not a troll, the drug has been proven by science in several studies to be useless. Now we're saying the Foundation is going to give that to humans who are dying instead of something with some hope of being useful. How is that not bad? How is it trolling for me to question it?

        • by Some Guy I Dont Know ( 6200212 ) on Saturday May 09, 2020 @02:00PM (#60041272)

          You haven't read the studies (or unreviewed pre-prints, which is what most of actually are) have you?

          HC and HC+AZ have been shown to have a significant benefit when used early in the infection. It's true about remdesivir as well.
          HC and HC+AZ have been shown to have no benefit, or to even be harmful, when used in the later stages of infection, especially after ventilation has occurred.

          This basic split in results - when the treatment is applied - is obvious when you actually read what people are putting out there. The VA 'study' for example not only gave treatments only to the sickest cases (late in the infection cycle), it actually moved patients from the control group to the treatment groups AFTER they were ventilated and dying. The Belgian and Israeli studies on HC+AZ and remdesivir, on the other hand, show good results by starting the treatment early.

          Nothing is a miracle, 100% effective cure, though. There is not, and will never be, such a thing.

        • by orlanz ( 882574 )

          No, it hasn't been "proven" to be useless. In vitro (test tube), it has proven as a candidate for vivo (living). It would be great if it works because it is a cheap readily available drug that has well established production, logistical, and consumption processes. Its side effects are also well known across a diverse body of people.

          But the reality is that the case isn't looking good for it. The studies thus far haven't proven but certainly have hinted that it is not useful. The zinc combo retroperspect

      • Are they actually looking at the complete combination of the three drugs or just hydroxychloroquine on its own again?

        The studies with positives results used a drug cocktail whereas the negative studies only looked at a single component. Seems skewed from the start.

        • by dgatwood ( 11270 )

          Again, if chloroquine is useless by itself and chloroquine + azithromycin is useless as a combination, but adding zinc sulfate improves the outcome, and zinc sulfate has been known for many, many years to reduce the severity and duration of viral infections by itself, what could possibly possess anyone to believe that chloroquine helps in combination with all those other things, rather than reaching the far more obvious conclusion, which is that zinc sulfate, given early, saves lives?

          • Again, if chloroquine is useless by itself and chloroquine + azithromycin is useless as a combination,

            If given to severely ill patients and not early on in the treatment.

            what could possibly possess anyone to believe that chloroquine helps in combination with all those other things

            Another comment here addresses that point: https://science.slashdot.org/c... [slashdot.org]

    • by hey! ( 33014 )

      Large as it is, the study in question is a retrospective study, not a controlled study; you can't be sure that the group of patients that got the treatment weren't somehow different from the patients who didn't. In fact it's almost certain they were different.

      I think, evidence-wise, this is enough to rule out the "silver bullet" scenario; it does not, however, rule out a modest effect, or perhaps even a more dramatic effect in certain kinds of patients.

      The gold standard for evidence is a randomized control

    • Shouldn't they be pursuing more promising trial treatments than wasting time and perhaps lives on something useless?

      To be clear, the Gates Foundation is not only studying HCQ. It is studying other treatments too. If anything it helps establish what does not work.

  • by account_deleted ( 4530225 ) on Saturday May 09, 2020 @11:49AM (#60040698)
    Comment removed based on user account deletion
    • It might be useful if used early enough to prevent the disease from progressing to a more serious state, but it seems useless if someone is already extremely ill. However, we don't have a controlled study to tell us if that's true. Statistical fluke seems less likely since there's more than one study that found an effect, but placebo is surprisingly powerful and could explain it.

      Even if it does have some benefits that can be proven, I'm not sure how useful it's going to be, at least for this particular p
    • by fermion ( 181285 )
      In the VA study more vets died using the drug. It is not conclusive but in general the protocol is when humans begin to die in higher rates in a study to end the study. The only reason the study was done, the only the guidance was temporally on the CDC website, was the ranting of a madman.

      We still have a pretty linear rate of infections and death in the US. We have tools we can use. The at home testing has been improved. There are some drugs that will be available in the near term. The consents by sane pe

    • Has any study looked at just Zn or Az? It would seem to me that HCQ alone does nothing. HCQ+Az does something. If Az alone does something maybe the factor is Az and not HCQ. At best that might show HCQ has a marginal effect with Az but comes with increased risk as drug combos normally do.
    • The controlled study (no, it doesn't have a placebo group, one doesn't do that with deadly diseases unless maybe one is Dr. Mengele) has been done, is peer-reviewed, and published on May 1 by Dr. Didier Raoult. I haven't found the publication on line, but Laura Ingraham had the account of it on her 10 PM Fox News slot last Wednesday night, which I transcribed from my DVR, and is here:

      " "This is the full peer-reviewed study by the renowned infectious disease specialist Dr. Didier Raoult and now it's publis

  • ... his hoard of that stuff is gonna lose him money.
    • ... his hoard of that stuff is gonna lose him money.

      HCQ is a cheap generic drug. India is a major manufacturer of generic drugs; they have the infrastructure to crank out millions of HCQ pills (they probably already do!). Nobody is going to make windfall profits on it. This is why big pharma would rather come up with something new, like Remdesivir, that they can sell for $1,000 per pill.

      • That's why they tried to corner the market on the stuff, and have trumpty hawking it and talking down the alternatives.  If it worked, it would have been hugely profitable for them.
  • by MikeDataLink ( 536925 ) on Saturday May 09, 2020 @12:07PM (#60040770) Homepage Journal

    I never said it worked.
    I never said we should try it.
    I never made any claims about it.
    I take no responsibility for it.

    - Trump in a few days

    • And I saved lives by recommending it!

  • by littlewink ( 996298 ) on Saturday May 09, 2020 @12:33PM (#60040860)

    They broke patients into two group: sickest and least sick. Then they gave HCQ only to sickest group. A quote from the study:

    Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360).

    Take this to an extreme: give HCQ to only the dead patients and deny HCQ to all living patients. In the end all the dead patients are, astonishingly, less healthy! Conclude that HCQ doesn't work!

    • In the end all the dead patients are, astonishingly, less healthy!

      Damn, the start of an apocalyptic event perhaps?

  • by john.r.strohm ( 586791 ) on Saturday May 09, 2020 @12:35PM (#60040878)

    This was not a randomly-assigned placebo-controlled double-blind trial. A wide variety of other studies, that appear to show that chloroquine and hydroxychloroquine are effective against SARS-nCOV-2, are routinely derided and called completely invalid for that precise reason. As such, this trial must be condemned, for precisely the same reason.

    The right answer is going to wind up being an 8-way double-blind controlled trial: Test all possible combinations of hydroxychloroquine, azithromycin, and zinc, and see what shows up.

    • One doesn't do placebo-controlled studies with deadly diseases since the outcome for the placebo group is known - death. That is unacceptable and equivalent to murder if one tries it.

  • Back to Clorox, I guess.

  • by Teppy ( 105859 ) on Saturday May 09, 2020 @12:45PM (#60040932) Homepage
    Although we don't yet have results from any clinical trials involving Hydroxychloroquine, we do have at least two observational studies for both HCQ and HCQ+Azithromycin that failed to find an effect. This is not surprising because it is believed that it is the Zinc that prevents virus replication, not Hydroxychloroquine. The Hydroxychloroquine is what allows Zinc ions to get into the not-yet-infected cells. Azithromycin is likely helpful against secondary bacterial infections of the lungs.

    Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro [plos.org]

    Chloroquine Is a Zinc Ionophore [nih.gov]

    Hydroxychloroquine + Zinc has shown a positive effect in a preliminary (not yet peer reviewed) report. This was an observational study, and it was among patients that were already sick enough to go to a hospital. So the treatment would be expected to have only a modest effect:

    Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients [medrxiv.org]

    The real study to watch is this one:

    A Study of Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for the Prevention of COVID-19 Infection [clinicaltrials.gov]

    It is looking at HCQ+Zn given prophylactically to healthcare workers and their families. I expect this study to show a positive result - they may have preliminary results within a few weeks.

    • I'm going to re-post this here because I think it needs to be said again:

      I'm just going to point this out because I know that many of you will argue this way and that about how this treatment "benefits" patients without any understanding of the underlying scientific knowledge about these drugs.

      Hydroxychloroquin is used to reduce the immune response. Specifically to decrease inflammation. Inflammation in the lung tissue and the consequential damage done by this immune response resulting in the patient presen

    • Dude, that's a _one year_ study. It lasts 26 weeks! It's sample is skewed toward emergency personnel whose immune systems are a little different than most. It's also a preventative study, not a prescription or treatment type.

      It makes perfect sense from the protecting Emergency Personnel view point and probably will have finds for further study in application to the general population. However, preliminary findings in a few weeks will be biased and potentially misleading.

  • Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine

    So the study compared standard care of covid-19 patients against the outcome of those who were already severaly ill and THEN given HCQ? I'm no statistician, nor am I a physician, but this seems to slant the study considerably. If they're only going to administer HCQ to the severely ill, then the study needs to remove data from anyone who wasn't severaly ill to get a fair assessment.

    All this study appears to have shown is that if you take all moderately ill patients who recover plus all severely ill patien

  • Look over the original study. The mode of action of hydroxychloroquine in fighting the virus is that makes it easier for zinc to enter the cells. However without supplements it renders the patient zinc deficient. This is pharmacology 101. If they used a group of severely ill patients as their group and never gave them zinc sulphate or similar, they may as well give them molecular-grade water while they're at it. You need to add the zinc.
    • by DRJlaw ( 946416 )

      However without supplements it renders the patient zinc deficient.

      Oh really? And who has measured this zinc deficiency? Do people taking HCQ for autoimmune disorders develop zinc deficiency?

      It's quite the hypothesis. Backed by nothing.

      • Where is your evidence it is backed by nothing? Seems like as empty an assertion as the one you are claiming OP has made.

        • by DRJlaw ( 946416 )

          Where is your evidence it is backed by nothing?

          "Prove a negative."

          No. That's his hypothesis/explanation. Prove that the patients were suffering a zinc deficiency.

          • I'm not an expert or involved in the trials so I can't provide that. Sorry. However if you google Hydroxychloroquine and zinc you will find many many results talking about using them in combination as a treatment for COVID-19.

            Maybe they're all just baseless, but I think it's more likely that where there is smoke, there is fire (that is, If a lot of experts are talking about a subject, it's probably because it's worth talking about).

  • Patients were not assigned evenly or randomly, instead high-risk patients were placed in the treatment groups:

    Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360).

    The groups were not fixed, nor were treatments applied equally or as reccommended:

    Patients were defined as receiving hydroxychloroquine if they were receiving it at study baseline

  • Comment removed (Score:3, Informative)

    by account_deleted ( 4530225 ) on Saturday May 09, 2020 @03:02PM (#60041464)
    Comment removed based on user account deletion
  • At what rate do people who are already being prescribed HCQ for other conditions (arthritis, lupus, etc.) get Covid-19?

Keep up the good work! But please don't ask me to help.

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