Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial

This is the study protocol for a phase II, double-blind, placebo-controlled trial of inhaled aviptadil — synthetic vasoactive intestinal peptide (VIP) — in 132 hospitalized COVID-19 patients at high risk for ARDS. The rationale documents VIP's biology: naturally concentrated in lung tissue, binding the same alveolar type II cells SARS-CoV-2 targets, reducing IL-6/TNF-alpha cytokines, and inhibiting viral replication in vitro. Patients inhale 67 micrograms of aviptadil or saline three times daily for up to 10 days, with time to clinical improvement as the primary endpoint; it builds on prior evidence that intravenous aviptadil improved COVID-19 respiratory failure outcomes.