Clinical trial NCT04421508: A Study to Assess Pulsed Inhaled Nitric Oxide vs Placebo in Subjects With Mild or Moderate COVID-19
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19
Coronavirus
Coronavirus Infection
Keywords: COVID
Sars-CoV-2
iNO
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
Lead sponsor: Bellerophon
Sponsor class: INDUSTRY
First posted: 2020-06-09
Enrollment: 191
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Number of Subjects Who Died or Had Respiratory Failure
timeFrame: Through Day 28
Secondary outcomes:
measure: Number of Subjects to Recover
timeFrame: Through Day 28
measure: Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
timeFrame: Day 7
measure: Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
timeFrame: Day 14
measure: Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
timeFrame: Day 28
measure: Number of Subjects Discharged Alive From Hospital
timeFrame: Through Day 28
measure: Duration of Hospitalization
timeFrame: Through Day 28
measure: All Cause Mortality
timeFrame: Through Day 28
measure: Difference in Proportion in RT-PCR Results at Discharge by Treatment Group
timeFrame: Through Day 28
Other outcomes:
measure: Number of Subjects With Adverse Events Leading to Study Drug Discontinuation
timeFrame: Through Day 28
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center
state: Arizona
city: San Diego
country: United States
facility: Kaiser Permanente - Zion Medical Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente - San Diego Medical Center
state: California
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: Chesterfield
country: United States
facility: The Lung Research Center (St. Luke's)
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico Hospital
state: New Mexico
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Toledo
country: United States
facility: Mercy Health St. Vincent Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Falls Church
country: United States
facility: INOVA
state: Virginia
city: Richmond
country: United States
facility: St. Francis Medical Center
state: Virginia
city: Richmond
country: United States
facility: Memorial Regional Medical Center
state: Virginia
city: Richmond
country: United States
facility: Chippenham Medical Center
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond
state: Virginia
city: Richmond
country: United States
facility: St. Mary's Hospital
state: Virginia
city: Richmond
country: United States
facility: Johnston-Willis Hospital
state: Virginia
Study officials:
affiliation: Bellerophon Therapeutics
name: Ashika Ahmed, MD
role: STUDY_DIRECTOR
References: