iNOPulse for COVID-19 (NO-COVER)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19; Hypoxemia; Hypoxemic Respiratory Failure
• Intervention / Treatment: Drug: Inhaled nitric oxide (iNO); Drug: Oxygen gas; Drug: Nitrogen gas

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33125
      • University of Miami Hospitals & Clinics

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:

1. Age 18 or above
2. Proven COVID-19 viral infection. Non-confirmed highly suspicious suspects may be enrolled.
3. Presence of radiographic findings compatible with pneumonia/pneumonitis.
4. Patients requiring at least 3 L/m oxygen via nasal canula to maintain O2 above 92%.
5. Female subjects of childbearing potential must have a negative pre-treatment pregnancy test (serum or urine).
6. Willing and able to comply with treatment schedule and study procedures.

Exclusion Criteria:

1. 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.
2. Participating in any other clinical trial for COVID-19
3. Pregnancy, or positive pregnancy test in a pre-dose examination.
4. Open tracheostomy.
5. Clinical contra-indication, as deemed by the PI or their designee.
6. 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.
7. Known history or clinical evidence of heart failure or left ventricular dysfunction (LVEF < 45%).
8. Significant hemoptysis
9. Unable to provide informed consent (proxy consent is acceptable if available)
10. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: iNOpulse Treatment Group; 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); iNO Pulse 250 mcg/kg ideal body weight (IBW)/hour; Drug: Oxygen gas; Supplemental oxygen administered via nasal cannula
ACTIVE_COMPARATOR: Placebo Group; 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: Oxygen gas; Supplemental oxygen administered via nasal cannula; Drug: Nitrogen gas; 250 mcg/kg ideal body weight (IBW)/hour

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Roger Alvarez
• Collaborators: Bellerophon Therapeutics
• Investigators: Principal Investigator: Roger A Alvarez, D.O., University of Miami

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2020
• Primary Completion (ANTICIPATED): June 1, 2021
• Study Completion (ANTICIPATED): July 15, 2021

Study Registration Dates

• First Submitted: May 20, 2020
• First Submitted That Met QC Criteria: May 20, 2020
• First Posted (ACTUAL): May 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 19, 2020
• Last Update Submitted That Met QC Criteria: August 17, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: COVID-19; respiratory failure; hypoxemia; inhaled nitric oxide
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Signs and Symptoms, Respiratory; COVID-19; Respiratory Insufficiency; Hypoxia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: 20200449

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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