Proponents of ivermectin for COVID-19 have long spoken about the expected review and meta-analysis led by Andrew Hill, PhD, of the University of Liverpool.
These results were finally published this week on Infectious Disease Open Forum, and the results are positive — but not without criticism, and most researchers still want results from randomized controlled trials.
The review and meta-analysis was conducted as part of the International Ivermectin Project Team from December 2020 to May 2021. Ivermectin proponents say Hill is conducting the analysis for WHO, but MedPage Today cannot confirm WHO involvement. Hill did not respond to an email request for comment.
Hill and colleagues assessed 24 randomized trials with a total of 3,328 patients involving some type of control, whether it was standard of care or other therapies. The sample size ranged from 24 to 400 participants. Eight of the studies have been published, nine are preprinted, six are unpublished results shared for analysis, and one is reported on the trial registration website.
In 11 trials (a total of 2,127 patients) focusing on moderate or severe infections, there was a 56% reduction in mortality (relative risk [RR] 0.44, 95% CI 0.25-0.77, P=0.004), with 3% of patients taking ivermectin dying compared to 9% of controls.
But the investigators noted that the number of deaths was small (128) and there was no difference between ivermectin and controls in the subgroup with severe disease. As for moderate disease, they reported a 70% improvement in survival with ivermectin (RR 0.30, 95% CI 0.15-0.58, P=0.0004).
The use of ivermectin was also associated with a reduction in recovery time of 1.58 days compared with controls (95% CI -2.8 to -0.35, P=0.01) and with a shorter duration of hospitalization (-4.27 days, 95% CI -8.6 to -0.06, P= 0.05).
However, the drug was not associated with a lower risk of hospitalization, although a sensitivity analysis that included hospitalization within 12 hours of taking the drug showed a reduction with ivermectin (RR 0.32, 95% CI 0.13–0.80). P= 0.01).
Many of the studies included in the analysis were not peer reviewed, which is a limitation; In addition, studies varied widely in terms of dose, duration of treatment, and inclusion criteria. The study also included a variety of controls, including hydroxychloroquine, lopinavir/ritonavir, standard of care, and placebo.
The authors concluded that their results “need to be validated in a larger confirmatory trial” – a fact agreed by David Boulware, MD, MPH, of the University of Minnesota, who is interested in evaluating ivermectin for COVID-19 outpatients.
On Twitter, Boulware pointed out that there was no mention of the patient receiving steroids, which could be a major confounder.
As for the outpatient findings, he noted that only two of the seven trials showed a reduction in symptom duration, and there was no analysis of whether the risk of hospitalization was reduced with early treatment.
“So, there is still a need for phase 3 randomized clinical trials testing early ivermectin treatment to be completed to illustrate what are the clinical benefits of early treatment? Faster resolution of symptoms? Fewer hospitalizations?” he tweets. “Personally, I’d like to see more of a separation of outpatient vs inpatient therapy, because blurring it all together doesn’t really help.”
“Of course, rolling out vaccinations as quickly and widely as possible would obviate the need to use ivermectin as a treatment,” he added. “So the big picture, vaccines are a better solution.”
Boulware notes that there are several ongoing phase III randomized controlled trials “that will provide definitive results,” including the UK PRINCIPLES outpatient trial which aims to enroll approximately 1,500 patients in its ivermectin arm.