iNOPulse for COVID-19

Study Overview
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Brief Summary
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This randomized, controlled trial will assess the efficacy and safety of pulsed iNO in subjects with COVID-19 who are hospitalized and require supplemental oxygen.

Official Title
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Randomized Controlled Trial Of A Delivered Continuously By Nasal Cannula For The Treatment Of Patients With COVID-19 And Mild To Moderate Hypoxemia Requiring Supplemental Oxygen

Conditions
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COVID-19, Hypoxemia, Hypoxemic Respiratory Failure

Intervention / Treatment
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* Drug: Inhaled nitric oxide (iNO)
* Drug: Nitrogen gas
* Drug: Oxygen gas


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or above Proven COVID-19 viral infection. Non-confirmed highly suspicious suspects may be enrolled. Presence of radiographic findings compatible with pneumonia/pneumonitis. Patients requiring at least 3 L/m oxygen via nasal canula to maintain O2 above 92%. Female subjects of childbearing potential must have a negative pre-treatment pregnancy test (serum or urine). Willing and able to comply with treatment schedule and study procedures. Exclusion Criteria: Patient with severe hypoxemia who are unable to maintain an oxygen saturation (SpO2) > 88% on a maximum supplemental oxygen of 6 L/m by nasal cannula and a non-rebreather facemask. Participating in any other clinical trial for COVID-19 Pregnancy, or positive pregnancy test in a pre-dose examination. Open tracheostomy. Clinical contra-indication, as deemed by the PI or their designee. Use of a nitric oxide donor agent such as nitroglycerin or drugs known to increase methemoglobin such as intravenous lidocaine, or topical benzocaine or dapsone at screening. Known history or clinical evidence of heart failure or left ventricular dysfunction (LVEF < 45%). Significant hemoptysis Unable to provide informed consent (proxy consent is acceptable if available) Any of the following conditions at time of possible enrollment: Fulminant Liver Failure, Acute Coronary Syndrome , Renal Failure requiring dialysis, Bacteremia, Shock, Cardiac arrest, Cardiac arrhythmia requiring acute treatment, Delirium / Encephalopathy, Severe Disseminated Intravascular Coagulation, Gastrointestinal hemorrhage, Hypoglycemia, Pneumothorax, Rhabdomyolysis / Myositis, Seizures, or Acute Stroke

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iNOpulse Treatment Group<br>Participants in this group will receive iNO delivered continuously together with supplemental oxygen by nasal cannula during hospitalization for up to 28 days. | Drug: Inhaled nitric oxide (iNO)<br>* iNO Pulse 250 mcg/kg ideal body weight (IBW)/hour<br>Drug: Oxygen gas<br>* Supplemental oxygen administered via nasal cannula<br>|
| Active Comparator: Placebo Group<br>Participants in this group will receive nitrogen gas delivered continuously together with supplemental oxygen by nasal cannula during hospitalization for up to 28 days | Drug: Nitrogen gas<br>* 250 mcg/kg ideal body weight (IBW)/hour<br>Drug: Oxygen gas<br>* Supplemental oxygen administered via nasal cannula<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events | As assessed per treating physician's discretion. | Up to 14 days | 
| Incidence of adverse events | Incidence of hypoxemia and hypotension as assessed per treating physician's discretion. | Up to 6 hours | 
| Incidence of methemoglobinemia | Incidence of increase to > 5% total methemoglobin as assessed by pulse oximetry. | Up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with progression of respiratory failure | Worsening respiratory status as defined by any one of the following: Implementation of High Flow Nasal Cannula (HFNC), non-rebreather mask, non-invasive ventilation, intubation and mechanical ventilation or need for intubation (in the event the patient is not intubated due to do not intubate (DNI) or do not resuscitate (DNR) status). | Up to 14 days | 
| Time until resolution of hypoxemia | The number of days until hypoxemia is resolved as per treating physician assessment | Up to 14 days | 
| Incidence of mortality | Incidence of death during hospitalization and after discharge up to 28 days | Up to 28 days | 
| Duration of hospitalization | Number of days of hospitalization | Up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypoxemia, respiratory failure, COVID-19, inhaled nitric oxide