Drug trial didn’t show benefit in COVID lung inflammation

A federally funded trial designed to mitigate inflammation in the lungs of acutely ill COVID-19 patients ultimately didn’t show that two drugs tested worked.

But the randomized, controlled trial proves useful should another coronavirus variant arise, said Aaron Barksdale, MD, vice chair of research for the department of emergency medicine.

The study recently appeared in Journal of the American Medical Association.

This study would eliminate the need for another extensive and robust trial of drugs like these, he said.

The study enrolled patients who had COVID-19 symptoms and a new oxygen requirement resulting in hospital admission.

The study, coordinated by Vanderbilt University, was conducted at nearly 40 sites. UNMC enrolled the majority of its patients from November 2021 to January 2022, during one of the most severe points of the Delta variant wave, Dr. Barksdale said. The emergency department continues to participate in a third drug arm within this ACTIV-4 (Accelerating COVID-19 Therapeutic Interventions) trial, funded by the National Heart, Lung and Blood Institute.

During those three months, Dr. Barksdale said, 37 patients were enrolled at UNMC, which was the fourth highest in the country.

Earlier phase trials suggested that the inflammation in the lungs from COVID-19 infection was the result of specific protein imbalances (angiotensin II and angiotensin 1-7), after SARS-CoV-2 entered pulmonary cells by binding to the human angiotensin-converting enzyme 2 (ACE2) receptor. These two investigational drugs attempted to restore that imbalance, therefore reducing the inflammatory process.

An interim analysis stopped the trial early when neither of the drugs — TRV-027 (an angiotensin II type 1 receptor-biased ligand) or TXA-127 (synthetic angiotensin [1-7]) — provided a significant benefit.

“If we ever have another variant of the coronavirus, and it enters the system the same way, we know this is not the route to go when investigating drug interventions,” Dr. Barksdale said.

Dr. Barksdale said collaboration from subinvestigators in several other departments, including critical care anesthesiology, critical care medicine, internal medicine and the emergency department, made the study a success. He also credited Brooklin Zimmerman, research coordinator from the department of emergency medicine. “We could not have had this success without her,” he said.