Intravenous Aviptadil for COVID-19 Associated Acute Respiratory Distress (COVID-AIV)
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|ClinicalTrials.gov Identifier: NCT04311697|
Recruitment Status : Not yet recruiting
First Posted : March 17, 2020
Last Update Posted : April 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Acute Respiratory Distress Syndrome Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) Corona Virus Infection||Drug: Aviptadil by intravenous infusion + maximal intensive care Drug: Normal Saline Infusion + Maximal intensive care||Phase 2|
Acute Respiratory Distress Syndrome is a known lethal complication of Corona Virus (COVID-19) infection. Conventional medical therapy, including intensive care and respiratory support is associated with a 50% mortality. Aviptadil, a synthetic form of Vasoactive Intestinal Polypeptide (VIP) has been awarded FDA Orphan Drug Designation for the treatment of ARDS.
Nonclinical studies demonstrate that VIP is highly concentrated in the lung, where it prevents NMDA-induced caspase-3 activation in the lung, inhibits IL6 and TNFa production, protects against HCl-induced pulmonary edema, These and other effects have been observed in numerous animal model systems of lung injury in mice, rats, guinea pigs, sheep, swine, and dogs. In these models, Aviptadil restores barrier function at the endothelial/alveolar interface and thereby protects the lung and other organs from failure.
Aviptadil is approved for human use in Europe and has a demonstrated 20 year history of safety in numerous trials for Sarcoid, Pulmonary Fibrosis, Bronchospasm, Erectile Dysfunction, and a phase I trial in ARDS. In that phase I trial, 8 patients with severe ARDS on mechanical ventilation were treated with ascending doses of VIP. Seven of the 8 patients were successfully extubated and were alive at the five day timepoint. Six left the hospital and one died of an unrelated cardiac event.
Five phase 2 trials of aviptadil have been conducted under European regulatory authority. Numerous healthy volunteer studies have shown that i.v. infusion of Aviptadil is well tolerated with few adverse effects including alterations in blood pressure, heart rate, or ECG. In addition to published studies of human use, Aviptadil has been used on a compounded basis in certain ICUs for many years in the belief that it preserves life and restores function in pulmonary hypertension, ARDS, and Acute Lung Injury (ALI).
In this study, patients who are hospitalized and intubated for ARDS secondary to COVID-19 infection will be randomly allocated to Aviptadil administered by intravenous infusion in addition to maximal intensive care vs. maximal intensive care alone. Primary endpoints will be improvement in blood oxygenation and mortality.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Multicenter trial, initially conducted at a single center with a safety/futility assessment following enrollment of 30 patients|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Randomized, placebo-controlled trial with identical drug and placebo infusion bags|
|Official Title:||Intravenous Aviptadil for COVID-19 Associated Acute Respiratory Distress|
|Estimated Study Start Date :||April 2020|
|Estimated Primary Completion Date :||August 2020|
|Estimated Study Completion Date :||September 2020|
Experimental: Aviptadil IV in escalating doses + maximal intensive care
Patients will be administered Aviptadil IV in escalating doses of 50 pmol, 100 pmol, 150 pmol/kg/hr
Drug: Aviptadil by intravenous infusion + maximal intensive care
Aviptadil by intravenous infusion + maximal intensive care (MIC). MIC is defined not to include extracorporeal mechanical oxygenation. Those requiring ECMO will be withdrawn from the study as treatment failures.
Experimental: Placebo + Maximal intensive care
Patients will first be treated with placebo infusion + maximal intensive care
Drug: Normal Saline Infusion + Maximal intensive care
Maximal intensive care (MIC). MIC is defined not to include extracorporeal mechanical oxygenation. Those requiring ECMO will be withdrawn from the study as treatment failures.
- Mortality [ Time Frame: 5 Days with followup through 30 days ]Mortality
- PaO2:FiO2 ratio [ Time Frame: 5 Days with followup through the end of telemetry monitoring ]Index of Respiratory Distress
- TNF alpha [ Time Frame: 5 Days ]TNF alpha levels as measured in hospital laboratory
- Multi-system organ failure free days [ Time Frame: 5 days with followup through 30 days ]Multi-system organ failure free days
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04311697
|Contact: Robert E Besthof, MIM||+14842546134 ext firstname.lastname@example.org|
|United States, Florida|
|Miller School of Medicine / University of Miami Medical Center|
|Miami, Florida, United States, 33136|
|Principal Investigator: Daniel H Kett, MD|
|Sub-Investigator: Richard B Silverman, MD|
|United States, New York|
|Robert I Grossman School of Medicine / NYU Langone Medical Center|
|New York, New York, United States, 10016|
|Principal Investigator: Daniel H Sterman, MD|
|Rambam Health Care Campus|
|Haifa, Israel, 3109601|
|Contact: Yaron Bar-Lavie, MD, FCCP 04-777-2601 email@example.com|
|Principal Investigator: Yaron Bar-Lavie, MD, FCCP|
|Study Chair:||Jonathan C Javitt, MD, MPH||NeuroRx, Inc.|