The paper at issue today reports the most thorough and well controlled study of the effect of ivermectin on Covid-19 around, and it was just published in JAMA Internal Medicine. What it supports, contra the claims of Joe Rogan, Bret and Heather Weinstein, and a whole slew of Republican loons, is that the drug ivermectin—as already asserted by the FDA—neither prevents nor cures covid-19. Or rather, this study shows that once adults over 50 who get the virus and are hospitalized with comorbidities, Ivermectin doesn’t help them get better. (An earlier study published in BMC Infectious Diseases, both randomized and double-blinded, and including a placebo, showed that taking ivermectin had no significant effect on keeping people out of the hospital.)
The upshot is that every well controlled study shows that ivermectin is useless in helping you once you get the virus. Another meta-analysis of reasonably well done studies that included prevention concluded that there was no good evidence that the drug even prevented infection. The only studies that may show value of ivermectin are those in which many participants have high loads of worms as comorbidities. In such studies (which don’t apply in the US or UK), the drug may, by helping you get rid of worms (see below), make recovery from covid more likely. But even in that case there’s no excuse not to get vaccinated. And of course you wouldn’t take ivermectin unless there was evidence you had worms.
Ivermectin is used in humans to cure parasitic worms and head lice, but can be dangerous if taken in doses high enough to kill viruses in vitro. Nevertheless, in this age of conspiracy theories and general lunacy, even credentialed scientists like the Weinsteins have recommended ivermectin and criticized vaccines, even though it’s beyond doubt that the vaccines prevent severe illness and hospitalization. You’d have to be crazy or paranoid to pass up vaccination in favor of ivermectin But thousands do it, so there you are.
With luck, you should be able to get the new study by clicking on the screenshot below, especially if you have the legal Unpaywall app. There’s also a link to the pdf, and if all else fails, make a judicious inquiry.
First, the background: the authors summarize what’s know about Ivermectin in studies to date. As I and others have mentioned before
Although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses. In 2021, 2 randomized clinical trials from Colombia and Argentina found no significant effect of ivermectin on symptom resolution and hospitalization rates for patients with COVID-19. A Cochrane meta-analysis also found insufficient evidence to support the use of ivermectin for the treatment or prevention of COVID-19. [JAC: The meta-analysis is linked above.]
The new study was done in Malaysia (other studies are ongoing, I believe), and iswasrandomized with respect to patient condition and age, but there was no placebo control. That is, half the infected patients were given “standard of care” (none were vaccinated) and the other half were given “standard of care” plus Ivermectin. The outcomes were followed over time. The result: not only did Ivermectin not work, but there was a slightly higher, though nonsignificant, risk of the ivermectin treated patients progressing to the phase that required supplemental oxygen. That is exactly the opposite of what you would expect if some patients were taking placebos, for you might expect that if there’s a placebo effect, then placebo-ingesting patients would do better than those not taking placebos (i.e., the patients in this study). But despite the absence of placebos, there was still no effect of ivermectin in this study using any measure of “disease progression”.
I’m not going to summarize the results in detail, because the authors do a good job of that themselves.
There are three summaries of the results. First, the “TL/DR” version:
Note below that the 490 patients observed were all over 50 and had documented comorbidities—factors that make them more susceptible to complications and death. Here is the protocol (indented, bolding is mine except in headers).
The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients’ symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease.
Interventions Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care (n = 241) or standard of care alone (n = 249). The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging.
Note again: no placebo pills were given. And here’s how they measured outcome:
Main Outcomes and Measures The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events.
The results are below. Note that slightly more patients in the ivermectin-dosed group (4% more) progressed to severe disease (i.e., requiring supplemental oxygen than those in the group treated the same but without ivermectin. Incorporating still other measures of “progression to severe disease,” there was again no significant difference, although there was slightly more deaths (nonsignificantly more) in the ivermectin versus control group. Finally, the most common side effect, diarrhea, was found more often in the ivermectin versus control group,but I can’t find the statistics for that difference.
Results Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group).
And the upshot:
Conclusions and Relevance In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19.
Here’s the entirety of the discussion (bolding mine); note that the authors, as is proper, point out the limitations of the work.
In this randomized clinical trial of early ivermectin treatment for adults with mild to moderate COVID-19 and comorbidities, we found no evidence that ivermectin was efficacious in reducing the risk of severe disease. Our findings are consistent with the results of the IVERCOR-COVID19 trial,17 which found that ivermectin was ineffective in reducing the risk of hospitalization.
Prior randomized clinical trials of ivermectin treatment for patients with COVID-19 and with 400 or more patients enrolled focused on outpatients.16,17 In contrast, the patients in our trial were hospitalized, which permitted the observed administration of ivermectin with a high adherence rate. Furthermore, we used clearly defined criteria for ascertaining progression to severe disease.
The pharmacokinetics of ivermectin for treating COVID-19 has been a contentious issue. The plasma inhibitory concentrations of ivermectin for SARS-CoV-2 are high; thus, establishing an effective ivermectin dose regimen without causing toxic effects in patients is difficult.27,28 The dose regimens that produced favorable results against COVID-19 ranged from a 0.2-mg/kg single dose to 0.6 mg/kg/d for 5 days29–32; a concentration-dependent antiviral effect was demonstrated by Krolewiecki et al.29 Pharmacokinetic studies have suggested that a single dose of up to 120 mg of ivermectin can be safe and well tolerated.33 Considering the peak of SARS-CoV-2 viral load during the first week of illness and its prolongation in severe disease,34 our trial used an ivermectin dose of 0.4 mg/kg of body weight daily for 5 days. The notably higher incidence of AEs [“adverse effects”] in the ivermectin group raises concerns about the use of this drug outside of trial settings and without medical supervision.
Our study has limitations. First, the open-label trial design might contribute to the underreporting of adverse events in the control group while overestimating the drug effects of ivermectin. Second, our study was not designed to assess the effects of ivermectin on mortality from COVID-19. Finally, the generalizability of our findings may be limited by the older study population, although younger and healthier individuals with low risk of severe disease are less likely to benefit from specific COVID-19 treatments.
Note as well the “limitatation” that placebos were not given. Another limitation is that this study didn’t assess the chance of getting infected in the first place when you take ivermectin, or of being hospitalized if you get infected, though other work (see above) has suggested no effect of ivermectin on either of these measures.
I was prepared to admit that my criticism of ivermectin was wrong had these properly-designed studies shown an effect, but of course because ivermectin is usually suggested as a substitute for getting vaccinated, the real thing you want to know is whether, compared to getting the jabs, you’re better off swallowing ivermectin. Given the efficacy of the vaccines, which has now been conclusively demonstrated (and yes, the effects wane over time, so we may need a yearly booster), I was already pretty sure that those who touted ivermectin as a better substitute for vaccination were wrong. But this study does nothing to convince me that I was wrong.
More studies will come out, and eventually we’ll have a pretty solid conclusion. And I’ll bet any reader $100 that it will show that ivermectin is no substitute for vaccination or the other new drugs that are being used to relieve symptoms and combat the virus.
The question now is whether people like Joe Rogan or, especially, Bret and Heather Weinstein will admit that ivermectin—at least in this study—has no effect. Ideally, scientists will admit when they’re wrong, and, as Richard Dawkins has emphasized, that is an admirable trait. Such admissions move science along faster than waiting for a generation wedded to an idea to die off and be replaced by those who have different ideas. Now I haven’t been wrong about ivermectin yet, but when I see a study showing it’s more efficacious than vaccines in keeping you out of the hospital, or alive, I’d like to think I’d say whose three words. Will the Weinsteins say them?
I predict no. We will see a lot of hemming and hawing frothe Quacksters, and perhaps qualifications like “well, the study showed X but didn’t show the real prediction, which is Y.” In fact, I don’t remember hearing anybody pushing quack remedies admit that they were wrong.
The reason I’m so dogged about this is because people who tout quack remedies when there are good ones can do harm. And it’s far worse if they push the quackery while wearing the mantle of science.
But listen up: STAY AWAY FROM THE DAMN IVERMECTIN!
h/t: Alex, Leslie