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



8 PagesPosted: 4 Aug 2020Last revised: 20 Aug 2020

Jihad G. Youssef

Houston Methodist Research Institute

Mukhtar Al-Saadi

Houston Methodist Hospital

Faisal Zahiruddin

Houston Methodist Hospital

Sarah Beshay

affiliation not provided to SSRN

Mohammad Bitar

affiliation not provided to SSRN

Jonathan Javitt

Johns Hopkins School of Medicine

Date Written: August 20, 2020


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.


Note: Funding: Funding:Research support was provided by the Cavendish Impact Foundation. Clinical trial funding was provided by Relief Therapeutics Holdings, AG, Geneva, which holds intellectual property related to the pharmacologic use of Aviptadil. 

Conflict of Interest: Author JCJ is employed bya pharmaceutical company that is currently conducting clinical trials of RLF-100in patients with COVID-19 and has a financial interest in the outcome of those clinical trials. Author MJJ was paid for medical writing by NeuroRx, Inc. Author JGY has received funding as an investigator for RLF-100 through his institution. 

Ethical Approval: Human subjects protection was overseen by the Institutional Review Board (IRB) of the Houston Methodist Hospital. 

Keywords: VIP, vasoactive intestinal peptide, aviptadil, SARS-CoV-2, corona virus, COVID-19, respiratory failure, IL6, ARDS

Previous News

RLF-100 (aviptadil) clinical trial showed rapid recovery from respiratory failure and inhibition of coronavirus replication in human lung cells

August 2, 2020, 4:00 PM

- Rapid recovery of patients on ventilators and ECMO (extracorporeal membrane oxygenation) was seen in patients with severe medical comorbidities after three days of treatment with RLF-100 under FDA Emergency Use IND authorization at multiple clinical sites

- Aviptadil is being developed as the first COVID therapeutic to block replication of the SARS-CoV-2 virus in human lung cells and monocytes

- RLF-100 is a patented formulation of aviptadil (synthetic human Vasoactive Intestinal Polypeptide VIP), which has been granted FDA Fast Track Designation, FDA emergency use IND authorization, and an expanded access protocol



Relief Therapeutics sees 60-70% chance of COVID-19 drug approval

AUGUST 8, 2020 / 2:52 AM

ZURICH (Reuters) - Relief Therapeutics’ chairman said he was optimistic its RLF-100 (aviptadil) drug will win approval for treating COVID-19 patients in a matter of months.

The Swiss group owns the rights to the drug in the United States and Europe. Its U.S. partner NeuroRx is running multicentre clinical trials here including a Phase IIb/III trial in patients who are severely ill because of the consequences of COVID-19, the respiratory disease caused by the new coronavirus.

“The active pharmaceutical ingredient of aviptadil has been used for a lot of years in different indications. From a safety standpoint we are quite optimistic,” Raghuram Selvaraju told Swiss newspaper The Market in an interview posted late on Friday.

“From an efficacy standpoint we need more data. I would say the probability at the moment stands at 60 to 70% that we will get the drug approved,” he added.


New York Times


FDA Lets NeuroRx, Relief Therapeutics Test RLF-100 in COVID-19 Patients

By Reuters

Aug. 6, 2020, 12:51 a.m. ET
  • ZURICH — The U.S. Food and Drug Administration has granted NeuroRx Inc Investigational New Drug (IND) permission to test RLF-100 (aviptadil) for inhaled use in patients with moderate and severe COVID-19 to prevent progression to respiratory failure, it and partner Relief Therapeutics Holdings said on Thursday.

The clinical trial of the inhaled formulation of RLF-100 is expected to begin on or before Sept. 1, a joint statement said.

They said aviptadil is shown as the first COVID therapeutic to block replication of the SARS-CoV-2 virus in human lung cells and monocytes while also preventing synthesis of cytokines in the lung. It is a patented formulation of aviptadil (synthetic human Vasoactive Intestinal Polypeptide, VIP), which has been granted FDA fast track designation, FDA emergency use IND authorisation, and an expanded access protocol.

(Reporting by Michael Shields; editing by Thomas Seythal)


Research Paper out from JohnHopkins,Houston Methodist Hospital and
New York University (NYU) - Langone Medical Center

Rapid Recovery from COVID-19 Respiratory Failure after treatment with Vasoactive Intestinal Peptide

RLF-100 (aviptaadil) Clinical Trail - FastTrack COVID drug

Drug that gives fellas a lift in the bedroom may also beat Covid, experts believe
Fox News Affiliate Coverage on drug Aviptadil/RLF-100

Dr. Yo talks the science behind RFL-100 in latest video.





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