iNOPulse for COVID-19 (NO-COVER)

• ClinicalTrials.gov Identifier: NCT04398290
• Recruitment Status: Withdrawn
• First Posted: May 21, 2020
• Last Update Posted: August 19, 2020
• Sponsor: Roger Alvarez
• Collaborator: Bellerophon Therapeutics
• Information provided by (Responsible Party): Roger Alvarez, University of Miami

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19; Hypoxemia; Hypoxemic Respiratory Failure	Drug: Inhaled nitric oxide (iNO); Drug: Nitrogen gas; Drug: Oxygen gas	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: December 1, 2020
• Estimated Primary Completion Date: June 1, 2021
• Estimated Study Completion Date: July 15, 2021

Arms and Interventions

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: Nitrogen gas; 250 mcg/kg ideal body weight (IBW)/hour; Drug: Oxygen gas; Supplemental oxygen administered via nasal cannula

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment emergent adverse events [ Time Frame: Up to 14 days ]
   As assessed per treating physician's discretion.
2. Incidence of adverse events [ Time Frame: Up to 6 hours ]
   Incidence of hypoxemia and hypotension as assessed per treating physician's discretion.
3. Incidence of methemoglobinemia [ Time Frame: Up to 14 days ]
   Incidence of increase to > 5% total methemoglobin as assessed by pulse oximetry.

Secondary Outcome Measures :

1. Number of participants with progression of respiratory failure [ Time Frame: Up to 14 days ]
   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).
2. Time until resolution of hypoxemia [ Time Frame: Up to 14 days ]
   The number of days until hypoxemia is resolved as per treating physician assessment
3. Incidence of mortality [ Time Frame: Up to 28 days ]
   Incidence of death during hospitalization and after discharge up to 28 days
4. Duration of hospitalization [ Time Frame: Up to 28 days ]
   Number of days of hospitalization

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Florida

University of Miami Hospitals & Clinics

Miami, Florida, United States, 33125

Sponsors and Collaborators

Roger Alvarez

Bellerophon Therapeutics

Investigators

• Principal Investigator: Roger A Alvarez, D.O.; University of Miami

More Information

• Responsible Party: Roger Alvarez, Assistant Professor of Clinical Medicine Pulmonary Vascular Diseases, University of Miami
• ClinicalTrials.gov Identifier: NCT04398290
• Other Study ID Numbers: 20200449
• First Posted: May 21, 2020
• Last Update Posted: August 19, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Roger Alvarez, University of Miami:

hypoxemia; respiratory failure; COVID-19; inhaled nitric oxide

Additional relevant MeSH terms:

COVID-19; Respiratory Insufficiency; Hypoxia; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Nitric Oxide; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Endothelium-Dependent Relaxing Factors; Vasodilator Agents; Gasotransmitters