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A Study to Assess Pulsed Inhaled Nitric Oxide vs Placebo in Subjects With Mild or Moderate COVID-19 (COViNOX)

Primary Purpose

COVID-19, Coronavirus, Coronavirus Infection

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
INOpulse
Placebo
Sponsored by
Bellerophon Pulse Technologies
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring COVID, Sars-CoV-2, iNO, INOpulse, Severe Acute Respiratory Syndrome (SARS) Pneumonia, Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV 2, COViNOX, pulsed inhaled nitric oxide, inhaled nitric oxide, portable pulsed inhaled nitric oxide, nitric oxide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed informed consent
  • At least 18 years old

  • Subjects must be hospitalized and have the following:

    • proven or high suspicion of SARS-CoV-2 infection and,
    • requiring oxygen supplementation defined as:
    • SpO2 ≤ 92% regardless of supplemental oxygen (ie on room air or on oxygen), or
    • SpO2 ≥ 92% on supplemental O2 and in the opinion of the Investigator it is not safe to decrease or remove the supplemental oxygen
    • require supplemental oxygen of no more than 10 L/minute, and
    • radiologic suspected or proven COVID-19 pneumonitis (chest x-ray or CT scan)
  • Female subjects must have a negative pregnancy test
  • Willing and able to comply with the treatment schedule and study procedures

Exclusion Criteria:

  • Participating in another clinical trial of an investigational treatment for COVID-19
  • Methemoglobin > 3%
  • Evidence of severe multi organ failure
  • Use of assisted ventilation prior to initiation of iNO
  • Pregnancy or positive pregnancy test pre-dose
  • Open tracheostomy
  • Chronic use of a nitric oxide donor agent such as nitroglycerin or drugs known to increase methemoglobin such as lidocaine, prilocaine, benzocaine, nitroprusside, isosorbide, or dapsone at screening
  • History or clinical evidence of systolic heart failure, left ventricular dysfunction (LVEF <40%)
  • Subjects reporting massive hemoptysis associated with the current illness or with radiologically proven pulmonary embolus

Sites / Locations

  • Banner University Medical Center
  • Kaiser Permanente - Zion Medical Center
  • Kaiser Permanente - San Diego Medical Center
  • University of Miami Health System
  • The Lung Research Center (St. Luke's)
  • University of New Mexico Hospital
  • The Ohio State University Wexner Medical Center
  • Mercy Health St. Vincent Medical Center
  • Temple University Hospital
  • Houston Methodist
  • INOVA
  • St. Francis Medical Center
  • Memorial Regional Medical Center
  • Chippenham Medical Center
  • Pulmonary Associates of Richmond
  • St. Mary's Hospital
  • Johnston-Willis Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Inhaled Nitric Oxide (iNO)

Placebo

Arm Description

Pulsed inhaled iNO 125 mcg/kg IBW/hour

Pulsed inhaled N2, 99.999% gas

Outcomes

Primary Outcome Measures

The Number of Subjects Who Died or Had Respiratory Failure
The number of subjects who died or had respiratory failure through Day 28

Secondary Outcome Measures

Number of Subjects to Recover
Number of subjects to recover, where recover is defined as attaining a NIAID Ordinal score of 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen or 8) Not hospitalized, no limitations on activities sustained through Day 28, or discharge from hospital without re admission for COVID.
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Number of Subjects Discharged Alive From Hospital
Number of subjects discharged alive from hospital through Day 28
Duration of Hospitalization
Duration of Hospitalization through Day 28
All Cause Mortality
All cause mortality through Day 28
Difference in Proportion in RT-PCR Results at Discharge by Treatment Group
Proportion of subjects with a positive RT-PCR result at baseline from a nasopharyngeal swab through Day 28 reported as a proportion of positive or negative RT-PCR testing.

Full Information

First Posted
June 5, 2020
Last Updated
February 17, 2023
Sponsor
Bellerophon Pulse Technologies
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1. Study Identification

Unique Protocol Identification Number
NCT04421508
Brief Title
A Study to Assess Pulsed Inhaled Nitric Oxide vs Placebo in Subjects With Mild or Moderate COVID-19
Acronym
COViNOX
Official Title
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo in Subjects With Mild or Moderate Coronavirus (COVID-19)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Futility
Study Start Date
July 12, 2020 (Actual)
Primary Completion Date
December 28, 2020 (Actual)
Study Completion Date
January 22, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bellerophon Pulse Technologies

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed inhaled iNO compared to placebo in subjects with COVID-19.
Detailed Description
This is a randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed iNO compared to placebo in subjects with COVID-19 who are hospitalized and require supplemental oxygen without assisted ventilation. Subjects will be randomized to receive placebo or iNO125 mcg/kg ideal body weight (IBW)/hour 24 hours daily up to 14 days or until resolution or discharge.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Coronavirus, Coronavirus Infection
Keywords
COVID, Sars-CoV-2, iNO, INOpulse, Severe Acute Respiratory Syndrome (SARS) Pneumonia, Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV 2, COViNOX, pulsed inhaled nitric oxide, inhaled nitric oxide, portable pulsed inhaled nitric oxide, nitric oxide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
191 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Inhaled Nitric Oxide (iNO)
Arm Type
Active Comparator
Arm Description
Pulsed inhaled iNO 125 mcg/kg IBW/hour
Arm Title
Placebo
Arm Type
Sham Comparator
Arm Description
Pulsed inhaled N2, 99.999% gas
Intervention Type
Combination Product
Intervention Name(s)
INOpulse
Intervention Description
Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Intervention Type
Combination Product
Intervention Name(s)
Placebo
Intervention Description
Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Primary Outcome Measure Information:
Title
The Number of Subjects Who Died or Had Respiratory Failure
Description
The number of subjects who died or had respiratory failure through Day 28
Time Frame
Through Day 28
Secondary Outcome Measure Information:
Title
Number of Subjects to Recover
Description
Number of subjects to recover, where recover is defined as attaining a NIAID Ordinal score of 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen or 8) Not hospitalized, no limitations on activities sustained through Day 28, or discharge from hospital without re admission for COVID.
Time Frame
Through Day 28
Title
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
Description
The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Time Frame
Day 7
Title
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
Description
The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Time Frame
Day 14
Title
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
Description
The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Time Frame
Day 28
Title
Number of Subjects Discharged Alive From Hospital
Description
Number of subjects discharged alive from hospital through Day 28
Time Frame
Through Day 28
Title
Duration of Hospitalization
Description
Duration of Hospitalization through Day 28
Time Frame
Through Day 28
Title
All Cause Mortality
Description
All cause mortality through Day 28
Time Frame
Through Day 28
Title
Difference in Proportion in RT-PCR Results at Discharge by Treatment Group
Description
Proportion of subjects with a positive RT-PCR result at baseline from a nasopharyngeal swab through Day 28 reported as a proportion of positive or negative RT-PCR testing.
Time Frame
Through Day 28
Other Pre-specified Outcome Measures:
Title
Number of Subjects With Adverse Events Leading to Study Drug Discontinuation
Description
Number of subjects with adverse events leading to study drug discontinuation through Day 28
Time Frame
Through Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent At least 18 years old Subjects must be hospitalized and have the following: proven or high suspicion of SARS-CoV-2 infection and, requiring oxygen supplementation defined as: SpO2 ≤ 92% regardless of supplemental oxygen (ie on room air or on oxygen), or SpO2 ≥ 92% on supplemental O2 and in the opinion of the Investigator it is not safe to decrease or remove the supplemental oxygen require supplemental oxygen of no more than 10 L/minute, and radiologic suspected or proven COVID-19 pneumonitis (chest x-ray or CT scan) Female subjects must have a negative pregnancy test Willing and able to comply with the treatment schedule and study procedures Exclusion Criteria: Participating in another clinical trial of an investigational treatment for COVID-19 Methemoglobin > 3% Evidence of severe multi organ failure Use of assisted ventilation prior to initiation of iNO Pregnancy or positive pregnancy test pre-dose Open tracheostomy Chronic use of a nitric oxide donor agent such as nitroglycerin or drugs known to increase methemoglobin such as lidocaine, prilocaine, benzocaine, nitroprusside, isosorbide, or dapsone at screening History or clinical evidence of systolic heart failure, left ventricular dysfunction (LVEF <40%) Subjects reporting massive hemoptysis associated with the current illness or with radiologically proven pulmonary embolus
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ashika Ahmed, MD
Organizational Affiliation
Bellerophon Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Banner University Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Kaiser Permanente - Zion Medical Center
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Facility Name
Kaiser Permanente - San Diego Medical Center
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
University of Miami Health System
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
The Lung Research Center (St. Luke's)
City
Chesterfield
State/Province
Missouri
ZIP/Postal Code
63017
Country
United States
Facility Name
University of New Mexico Hospital
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Mercy Health St. Vincent Medical Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43608
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Houston Methodist
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
INOVA
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
St. Francis Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23114
Country
United States
Facility Name
Memorial Regional Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23116
Country
United States
Facility Name
Chippenham Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23225
Country
United States
Facility Name
Pulmonary Associates of Richmond
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
St. Mary's Hospital
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
Johnston-Willis Hospital
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23235
Country
United States

12. IPD Sharing Statement

Learn more about this trial

A Study to Assess Pulsed Inhaled Nitric Oxide vs Placebo in Subjects With Mild or Moderate COVID-19

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