nVoq’s CEO, Charles Corfield, continues to provide transparency around drug research studies during the pandemic. Ivermectin was showing early promise in fighting the virus, but is the dosing within normal limits? Please check back weekly to read more of Charles’ thoughts.
Last week I wrote about the major embarrassment at two leading medical journals when they retracted two papers, after the plausibility of the data was questioned by many scientists and Surgisphere, the owner of the data, declined to make the data available for outside review. There were three covid-19 studies tied to Surgisphere, two were published (one about hydroxychloroquine and one about blood pressure medications), the third (about ivermectin as an anti-viral for covid-19) has now disappeared from the preprint servers. At first blush, the papers did not seem to be breaking radical new ground. There seemed to be other lines of evidence pointing in the same direction.
The paper on hydroxychloroquine posited that it was dangerous, which is plausible, since it can (uncommonly) induce heart arrhythmias. It is also known to have a narrow therapeutic range, meaning that overdosing is a risk (as people, who have self-administered, have found out). The paper on blood pressure medications posited that they don’t increase mortality, which was a worry in the medical community, but other researchers had already noted that they had not found any upticks in mortality in their patient populations. The third study was bullish on ivermectin. By way of background, ivermectin is a very effective anti-parasitic drug (a wonder drug if you will) and has rescued numerous people in tropical climes from chronic disability (e.g. river blindness) and death.
Its primary use in temperate regions is for the benefit of pets and livestock rather than humans. The Surgisphere paper seemed to be building on an earlier paper (by other researchers) which demonstrated that ivermectin could inhibit COVID-19 in cell cultures. The prospect of being able to use an existing, cheap drug with low toxicity for this pandemic is attractive and clinicians around the world have jumped on it. As of this morning a search for COVID-19 and ivermectin yields 23 registered trials (listed on clinicaltrials.gov). The art of fraud is to surround a fictional study with enough supporting evidence that the target buys the goods. The three studies extend the findings of preliminary studies in a way which takes them from being “working hypotheses” to “confirmed facts,” which would guarantee you a citation in every subsequent research paper and the social standing that goes with being one of the most cited scientists on the planet. It almost worked, but came unraveled because (apparently) fictitious data, cited in the papers, turned out to be at odds with verifiable facts that others knew.
Enough has already been said about hydroxychloroquine, so let me focus on ivermectin. The concentration of ivermectin required to suppress sars-cov-2 infection in the studied cell cultures was at first blush in line with the concentrations of many other therapeutic agents (); but this is where the story unravels. On closer inspection, this is larger than the highest concentrations seen in humans from any dose that has ever been investigated (and published). While it may be the case that humans could tolerate such high doses, there are good reasons to think they would prove toxic (ivermectin is, in essence, a nerve poison). We would be well outside the realm of repurposing a known drug, with a long history, and good safety record at its currently indicated dosing. In other words, the story is a little too good to be true. Since research teams have already registered clinical trials of ivermectin, they should proceed; but I would not expect them to produce game changing results. There is one upside: any patient who enters a trial with a pre-existing parasitic condition, and is assigned to the ivermectin treatment, may exit with one less condition to worry about, and that would be a happy outcome