Vasoactive Intestinal Peptide Promising Treatment for COVID-19 Respiratory Failure

Use of vasoactive intestinal peptide (VIP) to treat critical COVID-19 respiratory failure in patients with comorbidities has shown promise. Researchers presented findings from a prospective, open-label, administratively controlled trial that measured objective endpoints only at the American Thoracic Society (ATS) International Conference, held virtually from May 14 to May 19, 2021.

Recognizing that VIP blocks replication of the SARS-CoV-2 virus, inhibits cytokine synthesis, and upregulates surfactant production in human pulmonary cells, the researchers sought to establish the efficacy and safety of intravenous (IV) aviptadil — a synthetic VIP — for the improvement of survival and respiratory failure in patients with COVID-19. All of the patients in the current study had critical COVID-19 with severe comorbidities and were ineligible to participate in phase 3 trials of aviptadil. The participants were admitted to the intensive care unit (ICU) in June and July 2020, then were followed for at least 60 days after ICU admission.

Researchers compared 21 consecutively admitted patients with critical COVID-19 who were treated with IV aviptadil with 24 individuals with comparable comorbidities who received standard-of-care (SOC) treatment. Patients in the active treatment group received 3 successive 12-hour IV infusions of aviptadil at 50 pmol/kg/h, 100 pmol/kg/h, and 150 pmol/kg/h. The main outcomes measures included survival and recovery from respiratory failure.

Among the 21 patients treated with aviptadil, 19 survived to day 28, compared with 4 of the 24 individuals in the SOC group (90% vs 17%, respectively; P <.0001). Per Kaplan-Meier analysis, aviptadil therapy was associated with a 9-fold advantage in probability of survival (hazard ratio [HR], 0.113; 95% CI, 0.037-0.343). There was a similar 9-fold advantage observed with respect to cumulative probability of recovery from respiratory failure (HR, 0.115; 95% CI, 0.0254-0.5219).

Further, a mean 6.1-point difference was reported in the 10-point World Health Organization (WHO) Ordinal Scale for COVID-19 between those in the aviptadil group, who exhibited a significant mean 2.6-point improvement from time of ICU admission, compared with those in the control group, who exhibited a mean 3.5-point decrement (Wilcoxon rank sum: P <.001). A significant improvement in interleukin-6 levels was also reported with aviptadil treatment (P <.001).

The investigators concluded that aviptadil therapy was associated with a dramatic multidimensional treatment effect that was consistent with US Food and Drug Administration (FDA) and International Classification of Diseases, Tenth Edition (ICD-10) guidance for acceptance of externally-controlled, open-label trials in conditions with an increased risk of mortality.

Reference

Youssef J, Javitt J, Lavin P, et al. VIP in the treatment of COVID-19 respiratory failure in patients with severe comorbidities. Presented at: the American Thoracic Society (ATS) 2021 International Conference; May 14-19, 2021. Abstract A2478.