Rapid Recovery from COVID-19 Respiratory Failure after treatment with Vasoactive Intestinal Peptide

Abstract

Importance: There is currently no meaningfully effective drug for Critical COVID-19 with respiratory failure, particularly in highly comorbid patients with mortality in excess of 30%. Vasoactive Intestinal Peptide (VIP) blocks replication of the SARS-CoV-2 virus, inhibits cytokine synthesis, prevents cytopathy, and upregulates surfactant production in human pulmonary cells. Objective: To determine the safety and efficacy of intravenous Aviptadil (synthetic Vasoactive Intestinal Peptide) for improving the survival and recovery from respiratory failure in patients with Critical COVID-19 and severe comorbidity.Design: Prospective, open-label, administratively-controlled trial, measuring objective endpoints only. Patients were treated in June and July 2020 and followed for 60 days or more post ICU admission. Setting: Intensive care unit and step-down units of a quaternary care hospitalParticipants: 21 consecutively admitted patients with Critical COVID-19, treated with intravenous Aviptadil (synthetic VIP), compared to all patients with comparable comorbidity (n=24) from the same ICU, treated by the same clinical team, in the same time-frame who received maximal standard of care (SOC). Intervention: 3 successive 12-hour intravenous infusions of Aviptadil at 50/100/150 pmol/kg/hr.Main Outcome Measures: Survival, Recovery from Respiratory Failure, WHO 10 point ordinal scale. Results: Seventeen of 21 patients survived to day 60 in the aviptadil-treated group compared to 5 of 24 control patients (81% vs. 21%; PAt day 60, a similar 5.5-fold advantage was seen in the cumulative probability of Recovery from Respiratory Failure (55% vs 10%; P=.002) at 60 days . The hazard ratio is 0.115 (95% CL: 0.0254, 0.5219). Patients treated with Aviptadil were 7-times more likely (% WHO 0-1 57.1% (12/21) for aviptadil vs 8.3% (2/24) control, p-value = 0.0008) to achieve resolution of their symptoms.Comment: A dramatic multi-dimensional treatment effect was observed, consistent with FDA and ICH-10 guidance for acceptance of externally-controlled, open-label trials in high-lethality conditions.