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iNOPulse for COVID-19 (NO-COVER)

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Recruitment Status : Withdrawn (IRB AND FDA REVIEWS DEFERRED)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

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

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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

Resource links provided by the National Library of Medicine

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

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

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04398290

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United States, Florida
University of Miami Hospitals & Clinics
Miami, Florida, United States, 33125
Sponsors and Collaborators
Roger Alvarez
Bellerophon Therapeutics
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Principal Investigator: Roger A Alvarez, D.O. University of Miami
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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    Key Record Dates
Last Update Posted: August 19, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
respiratory failure
inhaled nitric oxide
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiratory Tract Infections
Pneumonia, Viral
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
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents