Treatment of Sepsis-related Acute Respiratory Distress Syndrome with Vasoactive Intestinal Peptide

Abstract

Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsis

Methods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery.

Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients.

Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.

Note: Funding: Funding for the research was provided to Prof. Sami Said by the National Institutes of Healthgrant HL-55849 and postdoctoral scholarship funding from the Egyptian Ministry of Higher Education. Support for this publication was provided by the Cavendish Impact Foundation and Relief Therapeutics Holdings, AG.

Conflict of Interest: Author JCJ is employed by NeuroRx, Inc., a pharmaceutical company that is developing VIP for human use together with Relief Therapeutics Holdings, AG. Author MCJ received compensation for medical writing.

Conflict of Interest: Human subjects were treated pursuant to IND 52,088 under a protocol approved by the Institutional Review Board of State University of New York Health Sciences Center, Stony Brook, NY.

Registration: This clinical trial was registered with www.clinicaltrials.gov under NCT00004494. Trial was registered before the first patient was enrolled.

Keywords: ARDS, VIP, Aviptadil, RLF-100, Acute Respiratory Distress Syndrome, Sepsis