Modified Clinical Trial Protocol Created in Response to Urgency of COVID-19 Pandemic

A new paper published online in the Annals of the American Thoracic Society describes a nimble, pragmatic, and rigorous multicenter clinical trial designed to meet urgent community needs in the face of the COVID-19 pandemic.

In the paper, Samuel Brown, MD, MS, and coauthors report on the design of a clinical trial, now under way, that they were able to quickly establish and adopt in community and academic hospitals throughout Utah to compare hydroxychloroquine and azithromycin as potential COVID-19 treatments.

“We developed the trial in response to local pressures for widespread, off-label use of these medications,” said Brown, director of pulmonary and critical care research at Intermountain Healthcare in Salt Lake City, who oversees the Center for Humanizing Critical Care at Intermountain Medical Center. “This, and past experience with Ebola, underscored the need for nimble, timely, rigorous controlled trials in a pandemic setting.”

The researchers hope to recruit up to 300 study participants with varying degrees of COVID-19 severity from within the Intermountain Healthcare and University of Utah health systems.

The study design differs from that of other randomized, controlled trials in that it does not have a placebo arm. “Placebos can take weeks or months to manufacture and distribute, and generally require a research pharmacy to manage,” Brown explained. “We were able to launch quickly because we didn’t have to wait for the placebo manufacture. We were also able to start the trial at hospitals that don’t have research pharmacies, including many community hospitals. It’s really been an all-hands-on-deck effort.”

In place of a placebo, the investigators chose to use a comparator drug—the antibiotic azithromycin. Because the drug showed anti-inflammatory pulmonary effects and other potential benefits in some previous trials, they felt it might have efficacy, and have a very low likelihood of harm due to its established safety profile.

Study participants are observed for 14 days, at which point their levels of improvement or decline are assessed (primary endpoint) based on the WHO COVID Ordinal Outcomes Scale. Secondary endpoints are calculated at 28 days based on whether they are hospital-free, ventilator-free, and Intensive Care Unit-free.

Edited by Gary Cramer