Increased Recovery and Survival in Patients With COVID-19 Respiratory Failure Following Treatment with Aviptadil: Report #1 of the ZYESAMI COVID-19 Research Group
9 Pages Posted: 11 May 2021
Date Written: April 23, 2021
Background: There is currently no approved drug for critically ill patients with respiratory failure caused by COVID-19. Vasoactive Intestinal Peptide (VIP) blocks replication of the SARS-CoV-2 virus in alveolar type II cells, inhibits cytokine synthesis, prevents cytopathy, and upregulates surfactant production.
Methods: A multicenter, randomized, placebo-controlled trial in 196 patients with PCR+ COVID-19 receiving intensive care at 10 U.S. hospitals – 6 tertiary care and 4 regional hospitals -- to determine whether intravenous aviptadil (synthetic VIP) is superior to placebo in achieving recovery from respiratory failure and survival at 60 days post treatment. Analysis was by modified intent to treat using a prespecified logistic regression model. Primary, prespecified endpoint was “alive and free from respiratory failure at day 60.”
Results: Across all patients and sites of care, patients treated with aviptadil were significantly more likely to be alive and free from respiratory failure at 60 days, compared to those treated with placebo (P=.02) and demonstrated improvement in survival alone (P<.001). Advantages in survival for aviptadil-treated patients were seen in both the subgroup classified as 2 on the National Institute of Allergy and Infectious Disease (NIAID) ordinal scale (58.6% vs. 0%; LR chi square=10.5, p=.001) and the NIAID=3 subgroup (83.1% vs. 62.8%; LR chi square=5.6, p=.03). Among patients who recovered successfully, those treated with Aviptadil had a median 10-day reduction in length of hospital stay compared to placebo patients (P=.025).
Comment: Treatment with aviptadil demonstrates multi-dimensional efficacy in improving the likelihood of recovery from respiratory failure and survival to 60 days, and markedly reduced hospital stay in critically ill patients with respiratory failure caused by COVID-19.
Note: Trial Registration: NCT04311697
Funding Statement: Clinical trial funding was provided by NeuroRx, Inc. and Relief Therapeutics, AG.
Declaration of Interests: Author JCJ is employed by NeuroRx, Inc. and is a shareholder in NeuroRx. Author PL is employed by Lavin Statistical Associates, which is paid by NeuroRx, Inc. for independent statistical analysis. Author MJM is a consultant to NeuroRx, Inc. Authors JGY, RAL, RL, DJP, JPF, and DJ received research support from NeuroRx via payments to their institutions.
Ethics Approval Statement: Clinicaltrials.gov documents approval by the Advarra IRB and each local IRB approved as well. Advarra IRB approval number: Pro00043143. Address:
Keywords: Aviptadil, COVID-19, Respiratory Failure, VIP, Vasoactive Intestinal Peptide
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