The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure

This controlled, randomized clinical trial evaluated intravenous aviptadil (VIP — vasoactive intestinal peptide) in 196 patients hospitalized with critical respiratory failure caused by COVID-19. The study was conducted across multiple centers in the United States during the pandemic, including patients on mechanical ventilation or high-flow oxygen.

The rationale for using aviptadil in COVID-19 lies in its action on VPAC1 and VPAC2 receptors abundantly expressed on type II alveolar pneumocytes — the same cells preferentially targeted by SARS-CoV-2. Endogenous VIP has potent anti-inflammatory properties, inhibiting the production of pro-inflammatory cytokines (TNF-alpha, IL-6, IL-8) and preventing pneumocyte apoptosis, acting directly against the "cytokine storm" characteristic of severe COVID-19.

The primary outcome showed that patients treated with IV aviptadil had a twofold greater probability of survival at 60 days compared to placebo (odds ratio of 2.0; 95% CI: 1.05-3.85; p=0.035). Beyond the survival improvement, there was a trend toward reduced mechanical ventilation time and shorter ICU stays in treated patients.

The safety profile was considered acceptable, with the most common adverse events being transient hypotension (expected from VIP's vasodilatory effect) and diarrhea. The study represented one of the first randomized evidence that modulation of the pulmonary inflammatory response via neuropeptides can be a viable strategy for severe viral respiratory failure, significantly expanding the therapeutic indications of aviptadil beyond its traditional applications.