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

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)

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Coronavirus Infection; Coronavirus
• Intervention / Treatment: Combination product: INOpulse; Combination product: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center
  • California
    • San Diego, California, United States, 92120
      • Kaiser Permanente - Zion Medical Center
    • San Diego, California, United States, 92123
      • Kaiser Permanente - San Diego Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Health System
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • The Lung Research Center (St. Luke's)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
    • Toledo, Ohio, United States, 43608
      • Mercy Health St. Vincent Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova
    • Richmond, Virginia, United States, 23226
      • St. Mary's Hospital
    • Richmond, Virginia, United States, 23114
      • St. Francis Medical Center
    • Richmond, Virginia, United States, 23116
      • Memorial Regional Medical Center
    • Richmond, Virginia, United States, 23225
      • Chippenham Medical Center
    • Richmond, Virginia, United States, 23226
      • Pulmonary Associates of Richmond
    • Richmond, Virginia, United States, 23235
      • Johnston-Willis Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Inhaled Nitric Oxide (iNO); Pulsed inhaled iNO 125 mcg/kg IBW/hour	Combination product: INOpulse; Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Sham Comparator: Placebo; Pulsed inhaled N2, 99.999% gas	Combination product: Placebo; Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Subjects Who Died or Had Respiratory Failure	The number of subjects who died or had respiratory failure through Day 28	Through Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Through Day 28
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.	Day 7
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.	Day 14
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.	Day 28
Number of Subjects Discharged Alive From Hospital	Number of subjects discharged alive from hospital through Day 28	Through Day 28
Duration of Hospitalization	Duration of Hospitalization through Day 28	Through Day 28
All Cause Mortality	All cause mortality through Day 28	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.	Through Day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Adverse Events Leading to Study Drug Discontinuation	Number of subjects with adverse events leading to study drug discontinuation through Day 28	Through Day 28

Collaborators and Investigators

• Sponsor: Bellerophon Pulse Technologies
• Investigators: Study Director: Ashika Ahmed, MD, Bellerophon Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2020
• Primary Completion (Actual): December 28, 2020
• Study Completion (Actual): January 22, 2021

Study Registration Dates

• First Submitted: June 5, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: COVID; SARS-CoV 2; nitric oxide; Severe Acute Respiratory Syndrome Coronavirus 2; iNO; INOpulse; pulsed inhaled nitric oxide; portable pulsed inhaled nitric oxide; Sars-CoV-2; Severe Acute Respiratory Syndrome (SARS) Pneumonia; COViNOX; inhaled nitric oxide
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: PULSE-CVD19-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No