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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
Sponsor:
Collaborators:
Relief Therapeutics Holding SA
Target Health Inc.
Lavin Consulting, LLC
Information provided by (Responsible Party):
NeuroRx, Inc.

Brief Summary:
Novel Corona Virus (COVID-19) is known to cause Acute Respiratory Distress Syndrome, that results in death of approximately 50% of those who develop ARDS, despite intensive care and mechanical ventilation. Patients with COVID-19 induced Acute Respiratory Distress Syndrome who are admitted for intensive care including endotracheal intubation and mechanical ventilation will be treated with Aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP) plus maximal intensive care vs. placebo + maximal intensive care. Patients will be randomized to intravenous Aviptadil will receive escalating doses from 50 -150 pmol/kg/hr over 12 hours.

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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
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
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. Mortality [ Time Frame: 5 Days with followup through 30 days ]
    Mortality

  2. PaO2:FiO2 ratio [ Time Frame: 5 Days with followup through the end of telemetry monitoring ]
    Index of Respiratory Distress


Secondary Outcome Measures :
  1. TNF alpha [ Time Frame: 5 Days ]
    TNF alpha levels as measured in hospital laboratory

  2. Multi-system organ failure free days [ Time Frame: 5 days with followup through 30 days ]
    Multi-system organ failure free days



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ARDS associated with COVID-19 infection
  • Medical necessity for endotracheal intubation and mechanical ventilation
  • Physician determination that patient is on maximal conventional medical therapy

Exclusion Criteria:

  • existing evidence of end-organ (renal, cardiac, hepatic, gastrointestinal failure)

Information from the National Library of Medicine

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


Contacts
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Contact: Robert E Besthof, MIM +14842546134 ext 701 rbesthof@neurorxpharma.com

Locations
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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         
Israel
Rambam Health Care Campus
Haifa, Israel, 3109601
Contact: Yaron Bar-Lavie, MD, FCCP    04-777-2601    y_barlavie@rambam.health.gov.il   
Principal Investigator: Yaron Bar-Lavie, MD, FCCP         
Sponsors and Collaborators
NeuroRx, Inc.
Relief Therapeutics Holding SA
Target Health Inc.
Lavin Consulting, LLC
Investigators
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Study Chair: Jonathan C Javitt, MD, MPH NeuroRx, Inc.

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Responsible Party: NeuroRx, Inc.
ClinicalTrials.gov Identifier: NCT04311697    
Other Study ID Numbers: COVID-AIV
First Posted: March 17, 2020    Key Record Dates
Last Update Posted: April 7, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by NeuroRx, Inc.:
COVID-19
ARDS
Aviptadil
Acute Respiratory Distress Syndrome
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Injury
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Virus Diseases
Thoracic Injuries
Wounds and Injuries
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Respiratory Tract Infections
Phentolamine
Vasoactive Intestinal Peptide
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents