Re-Use Old Drugs [for COVID] Quickly, While They Still Work!

EBM Focus - Volume 17, Issue 29

Reference: N Engl J Med 2022; 387:599-610

In December 2020, we published an EBM Focus about a “surprising benefit of fluvoxamine for COVID-19”. Due to a growing body of evidence, we would like to update our position at this time.

The New England Journal of Medicine just published another study evaluating the efficacy of three repurposed drugs to prevent progression to severe COVID: fluvoxamine, metformin, and ivermectin. The COVID-OUT trial enrolled 1,400 adult outpatients with overweight or obesity and recent-onset COVID, half of whom were vaccinated. The primary outcome was a composite of hypoxemia (≤ 93% oxygen saturation), emergency department visit, hospitalization, or death at 14 days.

We have some bad news: in this trial, nothing made a difference.

Science seems to have changed its mind. But did it really? We can think of a couple reasons why this most recent trial didn’t find a benefit when previous trials did: 1) Most patients were unvaccinated in earlier trials. 2) More recent strains of SARS-CoV-2 are less virulent. 3) Testing is more readily available than in the past, and newer studies identify and include more people with less severe disease. All of these factors suggest that a larger sample size may be necessary to prove a treatment effect. Science is messy and data is sometimes conflicting. The perception of changing tides or swinging pendulums can lead to skepticism, especially among lay people. Scientists try their best to interpret evidence and update recommendations, but it’s really important to understand the reasons for change. Being able to explain shifts in practice to your patients can facilitate better trust in medicine, and in you.

Clinical Take-Home Point: Don’t use fluvoxamine, metformin, or ivermectin for patients with COVID unless they have depression, diabetes, or a parasite.

EBM Pearl: Science doesn't change its mind. New information brings us closer to the truth. (And DynaMedex can help you keep up!)

Merci beaucoup to Armand Trousseau, who was the first to say “Use new drugs quickly, while they still work."

For more information, see the topic COVID-19 Management in DynaMed.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by Katharine DeGeorge, MD, MS, Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, Deputy Editor at DynaMed; Nicole Jensen, MD, Family Physician at WholeHealth Medical; Vincent Lemaitre, PhD, Senior Medical Writer at DynaMed; and Sarah Hill, MSc, Associate Editor at DynaMed.