Anti-Inflammatory Added to Remdesivir for Promising Study’s Second Phase
The first phase of a study of use of remdesivir in hospitalized COVID-19 patients raised hopes by reducing time to recovery. Now, in the second phase, researchers are combining the anti-viral with an anti-inflammatory, baricitinib, to see if that is even more effective than remdesivir alone. Here are more details.
BETHESDA, MD – With promising results from the use of remdesivir in patients hospitalized for COVID-19, public health officials have launched a study evaluating a treatment regimen of that investigational antiviral combined with the anti-inflammatory drug baricitinib.
The randomized controlled clinical trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), is now enrolling hospitalized adults with COVID-19 in the United States. Ultimately, the safety and effectiveness study is expected to be conducted at about 100 sites in the United States and internationally.
The research is part of the Adaptive COVID-19 Treatment Trial (ACTT), which began on Feb. 21 to evaluate remdesivir, an investigational broad-spectrum antiviral treatment developed by Gilead Sciences, Inc. With that trial closing to enrollment on April 19 after recruiting 1,063 participants at 47 U.S. and 21 international sites, an analysis by independent data and safety monitoring board (DSMB) indicated that patients who received remdesivir had a statistically significant shorter time to recovery compared to patients who received placebo. In ACCT 2, all participants will receive remdesivir or remdesivir plus baricitinib.
“We now have solid data showing that remdesivir diminishes to a modest degree the time to recovery for people hospitalized with COVID-19,” said NIAID Director Anthony S. Fauci, MD. “ACTT 2 will examine if adding an anti-inflammatory agent to the remdesivir regimen can provide additional benefit for patients, including improving mortality outcomes.”
Baricitinib, marketed as Olumiant, is licensed to Eli Lilly and Company by Incyte and is approved in the United States and more than 65 additional countries as a treatment for adults with moderately to severely active rheumatoid arthritis.
A NIAID press release points out that some COVID-19 patients experience acute respiratory distress syndrome (ARDS), in which inflammation of the lungs leads to shortness of breath and rapid breathing. Baricitinib, taken orally, inhibits cytokine signaling in the body that play roles in causing inflammatory responses.
“The putative benefit of baricitinib for COVID-19 has been described in a case series of critically ill patients who recovered from COVID-19,” it adds. The combination of remdesivir and baricitinib for COVID-19 has not been evaluated in a large, randomized controlled treatment trial, however.
Participants in the trial must have laboratory-confirmed SARS-CoV-2 infection and evidence of lung involvement, including a need for supplemental oxygen, abnormal chest X-rays, or illness requiring mechanical ventilation. Researchers emphasize that patients with confirmed infection but with mild symptoms, or no apparent symptoms, will not be included in the study.
In arm 1 of the double-blind study, participants will receive baricitinib tablets orally and intravenous (IV) remdesivir, while, in arm 2, patients will receive placebo tablets orally and IV remdesivir.
Remdesivir is administered as one 200-milligram (mg) IV dose followed by a 100-mg once-daily IV dose for the duration of hospitalization up to a 10-day total course of treatment. Baricitinib is administered as a 4-mg oral dose -- or crushed and given through a nasogastric tube, if necessary -- for the duration of hospitalization up to a 14-day total course of treatment.
Time to recovery is the primary end point, and researches will evaluate whether it is shorter in the combination arm (baricitinib plus remdesivir), as compared to remdesivir alone. For purposes of the study, recovery is defined as the patient being well enough for hospital discharge – i.e., the participant either no longer requires supplemental oxygen or ongoing medical care in the hospital, or is no longer hospitalized (with or without some limitation on activities). Recovery is evaluated up until day 29.
At the same time, the study team will look at a secondary goal, comparing patient outcomes at day 15 using an ordinal eight-point scale ranging from fully recovered to death. The trial will also compare other secondary outcome variables between treatment groups, including mortality alone.