Trial to compare dexamethasone and baricitinib in hospitalised COVID-19 patients

The US National Institute of Allergy and Infectious Diseases (NIAID) has announced that the fourth iteration of the Adaptive COVID-19 Treatment Trial (ACTT-4) has begun to enrol hospitalised adults with COVID-19 who require supplemental oxygen. The trial will enrol up to 1,500 patients at approximately 100 sites in the US and other countries.

The new participants will be randomised to receive either remdesivir and dexamethasone (a generic corticosteroid drug) or remdesivir and baricitinib (Olumiant). Baricitinib is a modulator of inflammation granted Emergency Use Authorization (EUA) in combination with remdesivir to treat suspected or laboratory confirmed COVID-19 in hospitalised patients aged two years and older who require supplemental oxygen, invasive mechanical ventilation or extracorporeal membrane oxygenation.

The trial is double-blinded for the dexamethasone and baricitinib components. Because dexamethasone is administered by intravenous (IV) infusion and baricitinib is a tablet taken orally, one group will receive oral baricitinib tablets and an IV placebo, while the others receive IV dexamethasone and oral placebo tablets. All participants will receive intravenous remdesivir.

ACTT-1 began in February, the final results of the trial comparing remdesivir to placebo in hospitalised adult COVID-19 patients were published in the New England Journal of Medicine. ACTT-2 evaluated baricitinib in combination with remdesivir in 1,033 adults hospitalised with COVID-19. The primary results of this study were announced in September and peer-reviewed results are forthcoming. ACTT-2 found that the combination of baricitinib and remdesivir shortened the recovery time relative to placebo and remdesivir. The EUA was in part based on these results.

Dexamethasone was evaluated in the global Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial. In that trial patients receiving dexamethasone demonstrated a lower mortality rate compared with patients receiving usual care.

To date, dexamethasone and baricitinib are the only two therapies that reduce inflammation that have demonstrated efficacy for the treatment of hospitalised adults with COVID-19 in large, randomised clinical trials. However, the NIAID said that the differences in study populations, mortality rates and endpoint data collected in the trials make it difficult to make firm conclusions about the value of the interventions. ACTT-4 aims to determine whether baricitinib or dexamethasone, when administered with remdesivir, is more effective at preventing hospitalised adults on supplemental oxygen from progressing to requiring mechanical ventilation or death.

Investigators will assess participants’ clinical status daily using an eight-point ordinal scale ranging from a return to baseline pre-COVID-19 status and not hospitalised to death. If discharged from the hospital, clinical status data will be collected during outpatient visits on days 15, 22, 29 and 60.

The trial is expected to take three to four months to fully enrol.