Updated review finds no evidence that ivermectin helps against Covid-19

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The authors took out fake and poorly conducted studies. It left them with 11 studies to review.
Photo by International Livestock Research Institute

Eleven reliable trials to date have produced no evidence that the horse deworming drug ivermectin benefits people with Covid-19, researchers report.

There remains no evidence to support the use of ivermectin for treating or preventing Covid-19 infection, according to the authors of an updated review examining the question.

The authors noted that evidence is limited to date, and evaluation of ivermectin is continuing in ongoing studies.

Ivermectin, a drug used to treat parasite infections in a range of animals, was screened in 2020 for activity against Covid-19. Laboratory tests suggested a weak effect on the SARS-CoV-2 virus in a test-tube, but the dose required for humans would need to be so large it was dismissed as an option.

Small trials suddenly appeared in the literature, suggesting large effects on mortality. This caused an explosion of interest, with some groups lobbying for it to be used worldwide.

Shortly after, several of these studies were shown to be fabricated; others had serious data errors and were poorly conducted.

Researchers from the Covid-19 Evidence Ecosystem project – an association of 20 German university hospitals and partner organizations that assess studies examining pressing questions about Covid-19 – collaborated with the Cochrane Infectious Disease Group, based at the Liverpool School of Tropical Medicine.

The result is an update to the original Cochrane Review, first published in 2021, that explored the effects of ivermectin in preventing and treating Covid-19 infection.  The original review was the most talked-about review in the history of the Cochrane Library.

Because of the many fake and poorly conducted studies, in this review update, the authors reappraised eligible studies specifically in relation to research integrity.

The authors included only randomized controlled trials that were prospectively registered in a study registry according to World Health Organisation guidelines for clinical trial registration.

They used a novel tool that also examined whether the studies had adequate ethics approval and whether the results were plausible. If there were any doubts, studies were put on hold until integrity could be assured by the authors.

The review authors included 11 trials with 3409 participants, investigating ivermectin plus standard of care compared to standard of care plus/minus placebo.

No study investigated ivermectin for prevention of infection or compared ivermectin to an intervention with proven effectiveness.

There were five studies treating participants with moderate Covid-19 in inpatient settings and six treating mild Covid-19 cases in outpatient settings.

Eight studies were double-blind and placebo controlled, three were open-label. Around 50% of the study results were assessed as having a low risk of bias.

Overall, the review found no evidence to support the use of ivermectin for treating or preventing Covid-19 infection.

“Overall, the outlook for ivermectin’s use to treat or prevent SARS-CoV-2 is poor,” the authors, Dr Maria Popp and Dr Stephanie Weibel, said. “While laboratory results showed some promise, real-life outcomes suggest no or very little impact on mortality rates, illness, and length of infection.”

In the review update, the authors’ confidence that ivermectin makes little or no difference has improved since the last review version.

Confidence remains low for many other outpatient and inpatient outcomes because there were only a few events measured. However, evaluation of ivermectin is continuing in 31 ongoing studies, and the review will be updated as results become available.

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