Document Type


Publication Date


Publication Title

CROI Conference on Retroviruses and Opportunistic Infections


california; fullerton; st jude; covid-19


COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vasoactive Intestinal Peptide (VIP) blocks replication of the SARS-CoV-2 virus in alveolar type II cells, inhibits cytokine synthesis, prevents cytopathy, and up regulates surfactant production. Synthetic VIP-aviptadil is a novel strategy to treat patients with COVID-19 and respiratory failure.

This was a prospective, multicenter, randomized, placebo-controlled trial with 196 patients, nasal swab PCR+ for COVID-19 receiving intensive care at 10 U.S. hospitals (6 tertiary care and 4 regional hospitals) to determine if intravenous aviptadil is superior to placebo in achieving recovery from respiratory failure and survival at 60 days post treatment. The analysis was by modified intent to treat (ITT) using a pre-specified logistic regression model. The primary pre-specified endpoint was being alive with no respiratory failure at day 60.

There were 213 subjects screened, with 203 eligible and 196 randomized and treated. Baseline characteristics were comparable except for worse NIAID severity for aviptadil (Table 1). All subjects were followed up to 60 days. A favorable trend (OR 1.63; P=.14) was seen for the primary endpoint at 60 days with significance achieved after adjusting for hospital setting. Overall, there was 2.0-fold increased odds of survival (95% CI 1.05-3.88; P<.035) for aviptadil at Day 60 controlling for baseline NIAID score. Odds of survival increased to over 4-fold after adjusting for site of care (Tertiary care vs regional hospital, OR 4.35 (95% CI 1.91, 9.90; P<.035). Logistic regression indicated aviptadil treated patients were also significantly more likely to be discharged earlier than placebo-treated patients (p=0.01). The most common adverse events noted were diarrhea (32.8% vs. 1.5%) and hypotension (26% vs.21.5%) for aviptadil vs. placebo. Additional adverse events occurring more frequently in aviptadil treated patients included acute kidney injury (23.7% vs 20%), hyperkalemia (12.2% vs 6.2%), and atrial fibrillation (11.5% vs 4.6%). Multiple organ dysfunction syndrome (6.9% vs 13.8%) and respiratory failure (12.2% vs 13.8%) occurred more commonly in placebo-treated patients.

Treatment with aviptadil demonstrates efficacy in improving the likelihood of recovering from respiratory failure, surviving to 60 days, and reducing hospital stay in critically ill patients with respiratory failure caused by COVID-19.

Clinical Institute





Infectious Diseases


Dushyantha Jayaweera, MD, MRCOG (UK), FACP1, J. Georges Youssef, MD 2,3, Richard A Lee, MD4, Philip Lavin, PhD, FASA, FRAPS5, Rainer Lenhardt, MD6, David J Park, MD7, Javier Perez Fernandez, MD8, Melvin L. Morganroth, MD9, Jonathan C. Javitt, MD, MPH 10,11 1University of Miami, Miller School of Medicine, 2Houston Methodist Pulmonary Transplant Center, Houston Methodist Hospital, Houston, Texas, USA, 3Department of Academic Pulmonology, Houston Methodist Hospital, Houston, Texas, 4University of California, Irvine, CA 5Boston Biostatistics Research Foundation, Framingham, MA, 6University of Louisville, Louisville, KY, 7Providence St Jude Medical Center/St Joseph Heritage Healthcare, Fullerton, CA, 8Baptist Hospital, Miami, FL, 9Oregon Clinic, Portland OR, 10NeuroRx, Inc. Wilmington, DE, 11Johns Hopkins University School of Medicine, Baltimore, MD