So while this is a small study and not a perfect match, it provides no evidence to show that the HCQ/AZ combination had any benefit at all.
But going on…
While we’re on the subject of QT prolongation, there’s this preprint from a medical team at NYU that was also treating patients with the same combination of drugs. In 84 patients, they found notable QT prolongation in about 30% of them, and another 11% were to a level (>500 milliseconds) that put them at a high risk for arrhythmia. This group’s mean age was 63, 74% male. No
But with that in mind, the authors report what looks like a bad interaction in that species between HCQ and metformin. And by “bad”, I mean about 30% mortality. If this translates at all to humans, it could be bad news, because (as mentioned above) diabetics look like a high-risk group and many patients may well have been taking metformin when they present at the hospital.
It’s weird and startling, though, if you haven’t had the opportunity to go back through clinical research (and even patient treatment) and seen how many things looked like they worked and really didn’t. It happens again and again. Alzheimer’s drugs, obesity drugs, cardiovascular drugs, osteoporosis drugs: over and over there have been what looked like positive results that evaporated on closer inspection. After you’ve experienced this a few times, you take the lesson to heart that the only way to be sure about these things is to run sufficiently powered controlled trials. No short cuts, no gut feelings – just data.
IMO doxycycline is a better bet than the malaria prophylactics that make you crazy.
Yes, and given the number of physicians trying it, the bias against publishing negative results, and our incredible ability to fool ourselves, at this point absence of evidence strongly indicates evidence of absence.
At this point, we have to keep in mind that 1 of every 20 studies that is properly done will find a therapeutic effect with a p of 0.05, so we can be statistically certain that such studies will be published.
One more point: someone last night was trying to tell me that my job was to “bring people hope” and that my attitude wasn’t helping with that task. Let me clear that up. I am not a physician, and I am not a clinician. I have spent my career in very early stage drug discovery, not at the bedside. Unfortunately, my lab skills are not well matched to the current epidemic – my own research has been more oncology-focused, and it’s way back in the pipeline. None of the last three companies I’ve worked for currently have any antiviral research. So as for my contribution to fighting the coronavirus, well, you’re looking a significant part of it right now. I can curate and annotate the news, add my own opinions after thirty years of drug discovery work and (I hope) make people smarter about what’s going on.
But keep in mind, most of what I’ve done, the great vast majority of what I’ve done over that thirty years has not worked in the clinic. Most things don’t . My job as a researcher has not to been to raise people’s hopes without data in hand, my job has been to try to produce such data so as to raise hopes with some reason to do so. When I see something to be hopeful about, I’ll say so, and when I think people are getting ahead of what we know, I’ll say that, too. Go back to the first things I wrote about the hydroxychloroquine/azithromycin work: I called it “potentially very interesting” and called for more data to see if it was real. That’s where I still am. Raising hopes just for the sake of raising hopes is not where I am, though, and in fact I find that whole idea to be cruel. We’re going to defeat this virus, this epidemic, by being as hard-nosed as we can be about collecting real data on real-world outcomes as quickly as efficiently as we can, not by talking vaguely about miracle cures and isn’t it something and wouldn’t it be great. You’ll need to go somewhere else for that. Try Dr. Oz, he’s good at that crap. I’ll stick to what I’m good at here.
Zinc was mentioned before in the discussion of hydroxychloroquine:
Again, anecdotes don’t cut it, but the theme of targeting viral RNA replication is a common one in the different trials that have been ongoing or being started. I believe both remdesivir and Actemra are nucleoside analogs of sorts. This harkens back to the first drug (as far as I can recall) used to treat AIDs - AZT.
Yes. And the Blaze has always been my favorite peer-reviewed medical journal. Not. (I almost used an emoticon but successfully resisted!)
That Blaze article includes this important offer: “Ditch the fake news ==> Click here to get news you can trust sent right to your inbox. It’s free!”
Irony abounds. (Of course, the reporting of what an actual doctor says about his actual opinion is not necessarily “fake news” per se—but you get the idea. Anecdotal accounts turned into reports that get people all excited, including some White House people, is not good.)
I think that is because there is evidence it conjugates to proteins in red blood cells, which take quite a while to clear. If there is a bad reaction however, they might clear quicker. It would be good to see some references on this.
We now have a very good idea why hydroxychloroquine doesn’t work in people, despite my friend’s 2005 paper showing that it worked beautifully to stop SARS-CoV-1 in cultured cells. Both SARS-CoV-1 and SARS-CoV-2 use a second pathway for getting into cells that is insensitive to hydroxychloroquine; moreover, that pathway is more important for SARS-CoV-2. This was conclusively demonstrated by swapping the relevant parts of the spike protein:
Hydroxychloroquine might still have some utility as an adjunct in combination with inhibiting TMPRSS2 protease, but this explains all of its clinical failures, @Giltil and @colewd.
Once again, science is more dependable than wishful thinking.
Two large randomized clinical trials (RECOVERY and SOLIDARITY) have both reported no benefit and potential risk from hydroxychloroquine. Derek Lowe has good summaries of both on his Science: In The Pipeline blog: The RECOVERY Trial Reports on Hydroxychloroquine, The SOLIDARITY Data. A combination of the two trials with 27 smaller randomized trials found no benefit from the drug (RR=1.10, 0.99-1.22). Due to the lack of efficacy and potential risk, both RECOVERY and SOLIDARITY have discontinued the hydroxychloroquine arms of their trials.