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History of Changes for Study: NCT04311697
Intravenous Aviptadil for COVID-19 Associated Acute Respiratory Distress (COVID-AIV)
Latest version (submitted February 23, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 14, 2020 None (earliest Version on record)
2 March 16, 2020 Contacts/Locations, Outcome Measures and Study Status
3 March 23, 2020 Arms and Interventions, Contacts/Locations, Outcome Measures, Study Description and Study Status
4 March 24, 2020 Study Design, Arms and Interventions, Outcome Measures, Study Description, Contacts/Locations and Study Status
5 April 1, 2020 Contacts/Locations, Oversight, Sponsor/Collaborators and Study Status
6 April 3, 2020 Contacts/Locations and Study Status
7 April 8, 2020 Contacts/Locations, Oversight and Study Status
8 April 21, 2020 Contacts/Locations, Study Description and Study Status
9 May 15, 2020 Recruitment Status, Study Status, Contacts/Locations, Study Design and Study Description
10 June 1, 2020 Recruitment Status, Contacts/Locations, Study Status, Conditions and Study Description
11 June 2, 2020 Arms and Interventions, Conditions, Study Description, Study Identification, Eligibility and Study Status
12 June 30, 2020 IPDSharing, Sponsor/Collaborators, Study Status and Contacts/Locations
13 July 27, 2020 Study Status
14 August 27, 2020 Contacts/Locations, Outcome Measures and Study Status
15 October 29, 2020 Study Status
16 November 25, 2020 Outcome Measures, Study Status, IPDSharing, Arms and Interventions, Study Design, Sponsor/Collaborators and Study Identification
17 December 25, 2020 Recruitment Status, Study Status, Study Design, Contacts/Locations, Arms and Interventions, Study Description and Study Identification
18 January 27, 2021 Contacts/Locations and Study Status
19 January 28, 2021 Contacts/Locations and Study Status
20 February 16, 2021 Study Status and Outcome Measures
21 February 23, 2021 Recruitment Status, Study Status and Outcome Measures
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Changes (Merged) for Study: NCT04311697
March 14, 2020 (v1) -- April 1, 2020 (v5)

Changes in: Study Status, Sponsor/Collaborators, Oversight, Study Description, Study Design, Arms and Interventions, Outcome Measures and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: COVID-AIV
Brief Title: Intravenous Aviptadil for COVID-19 Associated Acute Respiratory Distress (COVID-AIV)
Official Title: Intravenous Aviptadil for COVID-19 Associated Acute Respiratory Distress
Secondary IDs:
Open or close this module Study Status
Record Verification: March 2020
Overall Status: Not yet recruiting
Study Start: April 2020
Primary Completion: August 2020 [Anticipated]
Study Completion: September 2020 [Anticipated]
First Submitted: March 14, 2020
First Submitted that
Met QC Criteria:
March 14, 2020
First Posted: March 17, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
March 14, 2020 April 1, 2020
Last Update Posted: March 17 April 3, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: NeuroRx, Inc.
Responsible Party: Sponsor
Collaborators: Relief Therapeutics Holding SA
Target Health Inc.
Lavin Consulting, LLC
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: Novel Corona Virus (COVID-19) is known to cause Acute Respiratory Distress Syndrome, that results in mortality in 35% - death of approximately 50% of affected patients 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) and compared to historical controls plus maximal intensive care vs. placebo + maximal intensive care. Patients will be randomized to intravenous Aviptadil with escalation to nebulized Aviptadil vs will receive escalating doses from 50 -150 pmol/kg/hr over 12 hours. nebulized Aviptadil with escalation to intravenous Aviptadil.
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.

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 35%-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.

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. 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 , nebulization via the endotracheal tube, and both IV and endotracheal administration in addition to maximal intensive care vs. maximal intensive care alone. Primary endpoints will be improvement in blood oxygenation and mortality.

Open or close this module Conditions
Conditions: Acute Respiratory Distress Syndrome
Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Corona Virus Infection
Keywords: COVID-19
ARDS
Aviptadil
Acute Respiratory Distress Syndrome
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Crossover Parallel Assignment
Multicenter trial, initially conducted at a single center with a safety/futility assessment following enrollment of 30 patients
Number of Arms: 2
Masking: Single (Participant) Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 20 120 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Aviptadil IV followed by IV + Nebulization Experimental: Aviptadil IV in escalating doses + maximal intensive care
Patients will first be administered Aviptadil IV. Those showing inadequate clinical response at 48 hours will be advanced to Aviptadil IV plus nebulized Aviptadil per endotracheal tube 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 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.
Drug: Aviptadil by endotracheal nebulization
Aviptadil by endotracheal nebulization
Experimental: Nebulized Aviptadil followed by IV Aviptadil Experimental: Placebo + Maximal intensive care
Patients will first be administered nebulized Aviptadil per endotracheal tube. Those showing inadequate clinical response at 48 hours will be advanced to Aviptadil IV plus nebulized Aviptadil Patients will first be treated with placebo infusion + maximal intensive care
Drug: Aviptadil by intravenous infusion
Aviptadil by intravenous infusion
Drug: Aviptadil by endotracheal nebulization Drug: Normal Saline Infusion + Maximal intensive care
Aviptadil by endotracheal nebulization 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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Mortality
Mortality

[Time Frame: 5 Days 5 Days with followup through 30 days]
2. PO2 PaO2:FiO2 ratio
Index of Respiratory Distress

[Time Frame: 5 Days 5 Days with followup through the end of telemetry monitoring]
Secondary Outcome Measures:
3. TNF alpha
TNF alpha levels as measured in hospital laboratory

[Time Frame: 5 Days]
4. Multi-system organ failure free days
Multi-system organ failure free days

[Time Frame: 5 days with followup through 30 days]
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 100 Years
Sex: All
Gender Based:
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)
Open or close this module Contacts/Locations
Central Contact Person: Robert E Besthof, MIM
Telephone: +14842546134 Ext. 701
Email: rbesthof@neurorxpharma.com
Study Officials: Jonathan C Javitt, MD, MPH
Study Chair
Relief Therapeutics
Locations: United States, Florida
Miller School of Medicine / University of Miami Medical Center
Miami, Florida, United States, 33136
Contact:Principal Investigator: Daniel H Kett, MD
Contact:Sub-Investigator: Richard B Silverman, MD
United States, New York
Research Facility
New York, New York, United States, 10016
Robert I Grossman School of Medicine / NYU Langone Medical Center
New York, New York, United States, 10016
Contact:Principal Investigator: Daniel H Sterman, MD
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Contact:Principal Investigator: Ashok Balasubramanyam, MD
Israel
Rambam Health Care Campus
Haifa, Israel, 3109601
Contact:Contact: Ari Lipsky Yaron Bar-Lavie, MD, PhD +972526756090 lipsky.ari FCCP 04-777-2601 y_barlavie@ gmail rambam. com health.gov.il
Contact:Principal Investigator: Yaron Bar-Lavie, MD, FCCP
Open or close this module IPDSharing
Plan to Share IPD: Yes
Supporting Information:
Time Frame:
Access Criteria:
URL:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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