Back in January I wrote an article about four randomized controlled trials of ivermectin as a treatment for covid-19 that had at that time released their results to the public. Each of those four trials had promising results, but each was also too small individually to show any meaningful impact on the hard outcomes we really care about, like death. When I meta-analyzed them together however, the results suddenly appeared very impressive. Here’s what that meta-analysis looked like:
It showed a massive 78% reduction in mortality in patients treated with covid-19. Mortality is the hardest of hard end points, which means it’s the hardest for researchers to manipulate and therefore the least open to bias. Either someone’s dead, or they’re alive. End of story.
You would have thought that this strong overall signal of benefit in the midst of a pandemic would have mobilized the powers that be to arrange multiple large randomized trials to confirm these results as quickly as possible, and that the major medical journals would be falling over each other to be the first to publish these studies.
That hasn’t happened.
Rather the opposite, in fact. South Africa has even gone so far as to ban doctors from using ivermectin on covid-19 patients. And as far as I can tell, most of the discussion about ivermectin in mainstream media (and in the medical press) has centred not around its relative merits, but more around how its proponents are clearly deluded tin foil hat wearing crazies who are using social media to manipulate the masses.
In spite of this, trial results have continued to appear. That means we should now be able to conclude with even greater certainty whether or not ivermectin is effective against covid-19. Since there are so many of these trials popping up now, I’ve decided to limit the discussion here only to the ones I’ve been able to find that had at least 150 participants, and that compared ivermectin to placebo (although I’ll add even the smaller trials I’ve found in to the updated meta-analysis at the end).
As before, it appears that rich western countries have very little interest in studying ivermectin as a treatment for covid. The three new trials that had at least 150 participants and compared ivermectin with placebo were conducted in Colombia, Iran, and Argentina. We’ll go through each in turn.
The Colombian trial (Lopez-Medina et al.) was published in JAMA (the Journal of the American Medical Association) in March. There is one thing that is rather odd with this study, and that is that the study authors were receiving payments from Sanofi-Pasteur, Glaxo-Smith-Kline, Janssen, Merck, and Gilead while conducting the study. Gilead makes remdesivir. Merck is developing two expensive new drugs to treat covid-19. Janssen, Glaxo-Smith-Kline, and Sanofi-Pasteur are all developers of covid vaccines. In other words, the authors of the study were receiving funding from companies that own drugs that are direct competitors to ivermectin. One might call this a conflict of interest, and wonder whether the goal of the study was to show a lack of benefit. It’s definitely a little bit suspicious.
Anyway, let’s get to what the researchers actually did. This was a double-blind randomized controlled trial that recruited patients with mildly symptomatic covid-19 who had experienced symptom onset less than 7 days earlier. Potential participants were identified through a statewide database of people with positive PCR-tests. By “mildly symptomatic” the researchers meant people who had at least one symptom but who did not require high-flow oxygen at the time of recruitment in to the trial.
Participants in the treatment group received 300 ug/kg body weight of ivermectin every day for five days, while participants in the placebo group received an identical placebo. 300 ug/kg works out to 21 mg for an average 70 kg adult, which is quite high, especially when you consider that the dose was given daily for five days. For an average person, this would work out to a total dose of 105 mg. The other ivermectin trials have mostly given around 12 mg per day for one or two days, for a total dose of 12 to 24 mg (which has been considered enough because ivermectin has a long half-life in the body). Why this study gave such a high dose is unclear. However, it shouldn’t be a problem. Ivermectin is a very safe drug, and studies have been done where people have been given ten times the recommended dose without any noticeable increase in adverse events.
The stated goal of the study was to see if ivermectin resulted in more rapid symptom resolution than placebo. So participants were contacted by telephone every three days after inclusion in the study, up to day 21, and asked about what symptoms they were experiencing.
398 patients were included in the study. The median age of the participants was 37 years, and they were overall very healthy. 79% had no known co-morbidities. This is a shame. It means that this study is yet another one of those many studies that will not be able to show a meaningful effect on hard end points like hospitalization and death. It is a bit strange that studies keep being done on young healthy people who are at virtually zero risk from covid-19, rather than on the multi-morbid elderly, who are the ones we actually need an effective treatment for.
Anyway, let’s get to the results.