lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Rapid Recovery from COVID-19 Respiratory Failure with Comorbidity in 21 Patients Treated with Vasoactive Intestinal Peptide

10 Pages Posted: 18 Sep 2020

See all articles by Jihad G. Youssef

Jihad G. Youssef

Houston Methodist Research Institute

Mukthar Al-Saadi

Houston Methodist Hospital

Faisal Zahiruddin

Houston Methodist Hospital

Sarah Beshay

Houston Methodist Hospital

Mohammad Bitar

Houston Methodist Hospital

Jonathan Javitt

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

More...

Multiple version iconThere are 2 versions of this paper

Abstract

Background:  Vasoactive Intestinal Peptide (VIP) is known to bind to and protect Alveolar Type II cells by blocking replication of the SARS-CoV-2 virus, inhibiting cytokine synthesis, preventing cytopathy, and upregulating surfactant production. RLF-100™ (aviptadil), a synthetic form of VIP has been granted Fast Track Designation for treating Critical COVID-19 with Respiratory Failure and is currently in phase 2/3 placebo-controlled trials. 

Methods: Case series of 21 consecutive patients with Acute Respiratory Failure in Critical COVID-19 and multiple co-morbidities, treated with intravenous VIP.  Sixteen patients were treated with mechanical ventilation and five with extracorporeal membrane oxygenation (ECMO). 

Results: So far, 19 of 21 patients have survived. Improved radiographic appearance was seen in both lungs of 17 patients and in one lung of 2 patients. A mean 292% increase in PaO2:FiO2 ratio was seen with complete remission from respiratory failure in 9 patients and ongoing improvement in 10. Seven patients were discharged from the hospital, 7 sent to intermediate care, and 5 remain in the ICU. Three of 5 patients on ECMO have been decannulated and two have been discharged. A 75% (95% CI±3%: P<.001) reduction in IL-6 was seen with corresponding decrease in C-reactive protein. A median 4 point reduction in the NIAID Ordinal Scale was observed (P<.01).   

Comment: The short term outcomes in these 21 patients represent a dramatic response in patients who are excluded from all other trials of COVID therapeutics. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect.

Trial Registration: Expanded Access Protocol (EAP), NCT04453839.

Funding Statement: Research support was provided by the Cavendish Impact Foundation and Princeton Alumni Angels. Clinical trial funding was provided by Relief Therapeutics Holdings, AG, Geneva and NeuroRx, Inc.

Declaration of Interests: Author JCJ is employed by NeuroRx, Inc., a pharmaceutical company that is currently conducting clinical trials of RLF-100 in patients with COVID-19 and is Vice Chairman Elect of Relief Therapeutics, all other authors have no declaration to declare.

Ethics Approval Statement: Human subjects’ protection was overseen by Advarra IRB, the Institutional Review Board (IRB) of the Houston Methodist Hospital, and by an independent Data Monitoring Committee.

Keywords: VIP, Vasoactive Intestinal Peptide, Aviptadil, COVID-19, SARS-CoV-2, Antiviral

Suggested Citation

Youssef, Jihad G. and Al-Saadi, Mukthar and Zahiruddin, Faisal and Beshay, Sarah and Bitar, Mohammad and Javitt, Jonathan, Rapid Recovery from COVID-19 Respiratory Failure with Comorbidity in 21 Patients Treated with Vasoactive Intestinal Peptide. Available at SSRN: https://ssrn.com/abstract=3679909 or http://dx.doi.org/10.2139/ssrn.3679909

Jihad G. Youssef

Houston Methodist Research Institute ( email )

6670 Bertner Ave
Houston, 77030
United States

Mukthar Al-Saadi

Houston Methodist Hospital

6621 Fannin St
Houston, TX 77030
United States

Faisal Zahiruddin

Houston Methodist Hospital

6621 Fannin St
Houston, TX 77030
United States

Sarah Beshay

Houston Methodist Hospital

Mohammad Bitar

Houston Methodist Hospital

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

Click here to go to TheLancet.com

Paper statistics

Abstract Views
7,487
Downloads
1,034
PlumX Metrics