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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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COVID-19, Coronavirus, Coronavirus Infection

Intervention / Treatment
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* Combination Product: INOpulse
* Combination Product: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iNO, COVID, Sars-CoV-2, 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