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

See all articles by Jihad G. Youssef

Jihad G. Youssef

Houston Methodist Research Institute

Richard Lee

University of California, Irvine

Jonathan Javitt

Johns Hopkins School of Medicine; Potomac Institute for Policy Studies; NeuroRx

Philip Lavin

Boston Biostatistical Research Foundation

Rainer Lenhardt

University of Louisville School of Medicine

David J. Park

Providence St. Jude Medical Center/St. Joseph Health Care

Javier Perez Fernandez

Medical Director, Critical Care

Melvin Morganroth

Oregon Clinic

Dushyantha Jayaweera

University of Miami - Miller School of Medicine

Date Written: April 23, 2021

Abstract

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

Suggested Citation

Youssef, Jihad G. and Lee, Richard and Javitt, Jonathan and Lavin, Philip and Lenhardt, Rainer and Park, David J and Perez Fernandez, Javier and Morganroth, Melvin and Jayaweera, Dushyantha, Increased Recovery and Survival in Patients With COVID-19 Respiratory Failure Following Treatment with Aviptadil: Report #1 of the ZYESAMI COVID-19 Research Group (April 23, 2021). Available at SSRN: https://ssrn.com/abstract=3830051 or http://dx.doi.org/10.2139/ssrn.3830051

Jihad G. Youssef

Houston Methodist Research Institute ( email )

6670 Bertner Ave
Houston, 77030
United States

Richard Lee

University of California, Irvine ( email )

Irvine, CA 92697
United States

Jonathan Javitt (Contact Author)

Johns Hopkins School of Medicine ( email )

Baltimore, MD

Potomac Institute for Policy Studies ( email )

901 N. Stuart Street
Suite 200
Arlington, VA 22203
United States

NeuroRx ( email )

NeuroRx, Inc.
913 N. Market Street
Wilmington, DE 19801
United States

HOME PAGE: http://www.neurorxpharma.com

Philip Lavin

Boston Biostatistical Research Foundation ( email )

3 Cahill Drive
Framingham, MA 01702
United States

Rainer Lenhardt

University of Louisville School of Medicine ( email )

550 South Jackson Street
Louisville, KY 40202
United States

David J Park

Providence St. Jude Medical Center/St. Joseph Health Care ( email )

101 E Valencia Mesa Dr
Fullerton, CA 92835
United States

Javier Perez Fernandez

Medical Director, Critical Care ( email )

1691 Michigan Avenue
Fifth Floor
South Miami, FL 33139
United States

Melvin Morganroth

Oregon Clinic ( email )

Portland, OR
United States

Dushyantha Jayaweera

University of Miami - Miller School of Medicine ( email )

Miami, FL 33136
United States

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