RESUMO
RationaleThere are few treatment options for severe COVID-19 pneumonia. Opaganib is an oral treatment under investigation. ObjectiveEvaluate opaganib treatment in hospitalized patients with severe COVID-19 pneumonia. MethodsA randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 60 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n=230; 500mg twice daily) or matching placebo (n=233) for 14 days. Main Outcome MeasurementsPrimary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28- and 42-days. Main ResultsPre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FiO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FiO2 levels at or below the median value ([≤]60%) had better outcomes after opaganib treatment (n=117) compared to placebo (n=134). The proportion of patients with [≤]60% FIO2 at baseline that no longer required supplemental oxygen ([≥]24 hours) by day 14 of opaganib treatment increased (76.9% vs 63.4%: p-value =0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs 17.91%; p-value=0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs 16.7%; p-value=0.019) by day 42. No new safety concerns observed. ConclusionsPost-hoc analysis supports opaganib benefit in COVID-19 severe pneumonia patients that require lower supplemental oxygen ([≤]60% FiO2). Further studies are warranted. Trial registration numberNCT04467840
