Aviptadil for Severely Ill Inpatients With COVID-19 (An ACTIV-3b/TESICO Treatment Trial)

This is a treatment trial of the ACTIV-3b/TESICO master protocol (NCT04843761) to evaluate the safety and efficacy of Aviptadil at improving outcomes for patients with acute respiratory failure related to COVID-19. This protocol will be adaptive, randomized, blinded and initially placebo-controlled. Participants will receive standard of care (SOC) treatment as part of the protocol. This protocol will be conducted in up to several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs. The protocol is for a Phase 3 study. Participants will be followed for 90 days following randomization for the primary endpoint and most secondary endpoints. Selected secondary endpoints will be measured at 180 days. This study is planned to provide 80% power to detect an odds ratio of 1.5 for improvement in recovery status at Day 90 for Aviptadil versus placebo with use of the ordinal outcome. The planned sample size is 320 participants. Sample size may be re-estimated before enrollment is complete based on an assessment of whether the pooled proportions of the outcome are still consistent with adequate power for the hypothesized difference measured by the odds ratio. Randomization will be stratified by study site pharmacy and by receipt of invasive mechanical ventilation, or ECMO (extracorporeal membrane oxygenation) at enrollment. Other agent-specific stratification factors may be considered. An independent Data and Safety Monitoring Board (DSMB) will review interim safety and efficacy data at least monthly. Pre-specified guidelines will be established to recommend early stopping of the trial for evidence of harm or substantial efficacy. The DSMB may recommend discontinuation of an investigational agent if the risks are judged to outweigh the benefits.