A new trial focused on dexamethasone, remdesivir, and baricitinib use on COVID-19 is underway at the National Institute of Allergy and Infectious Diseases (NIAID), with plans to enroll as many as 1,500 hospitalized adult patients.
The fourth iteration of the Adaptive COVID-19 Treatment Trial (ACTT-4) will span approximately 100 sites worldwide. During treatment, patients will be divided into two groups. One group will be given the corticosteroid dexamethasone and remdesivir, the broad-spectrum antiviral created by Gilead Sciences, Inc. The second group will be issued remdesivir and anti-inflammatory baricitinib.
While dexamethasone is a generic drug, remdesivir and baricitinib are operating under the U.S. Food and Drug Administration (FDA) Emergency Use Authorizations. Neither investigators nor participants will know who has been given dexamethasone and baricitinib, although the former is administered by intravenous infusion and the other is an oral tablet. To guarantee this secrecy, one group will be given an IV placebo and the other given oral placebo tablets in addition to their actual treatments.
As a program, ACTT first began in February, when remdesivir was compared to a placebo among hospitalized adult COVID-19 patients. While it was shown to shorten the recovery time, its successes were moderate, and efforts were undertaken to pair it with other drugs in further testing. So far, dexamethasone and baricitinib are the only two anti-inflammatories that have shown efficacy among hospitalized COVID-19 patients in large, randomized trials.
Dexamethasone was previously evaluated in a global trial sponsored by the University of Oxford, while baricitinib was tested in combination with remdesivir in ACTT-2. However, differences in study populations, mortality rates, and endpoint data collected over these trials reaffirmed a need for investigators to launch another trial that could conclude their efficacy in preventing hospitalized adults from dying or requiring mechanical ventilation when paired with remdesivir.
Data will be collected for 60 days following patient discharge. The trial will evaluate the proportional difference between those who survive without requiring invasive mechanical ventilation and compare overall clinical status at day 15 in each group. Enrollment, however, should take approximately three to four months.