Trial Outcomes & Findings for A Study to Assess Pulsed Inhaled Nitric Oxide vs Placebo in Subjects With Mild or Moderate COVID-19 (NCT NCT04421508)

NCT ID: NCT04421508

Last Updated: 2023-02-21

Results Overview

The number of subjects who died or had respiratory failure through Day 28

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

191 participants

Primary outcome timeframe

Through Day 28

Results posted on

2023-02-21

Participant Flow

Participant milestones

Participant milestones
Measure	Inhaled Nitric Oxide (iNO) Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Overall Study STARTED	95	96
Overall Study COMPLETED	91	95
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

1 age value missing in Placebo group

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inhaled Nitric Oxide (iNO) n=95 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=96 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Total n=191 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=95 Participants • 1 age value missing in Placebo group	0 Participants n=95 Participants • 1 age value missing in Placebo group	0 Participants n=190 Participants • 1 age value missing in Placebo group
Age, Categorical Between 18 and 65 years	62 Participants n=95 Participants • 1 age value missing in Placebo group	59 Participants n=95 Participants • 1 age value missing in Placebo group	121 Participants n=190 Participants • 1 age value missing in Placebo group
Age, Categorical >=65 years	33 Participants n=95 Participants • 1 age value missing in Placebo group	36 Participants n=95 Participants • 1 age value missing in Placebo group	69 Participants n=190 Participants • 1 age value missing in Placebo group
Age, Continuous	58.0 years STANDARD_DEVIATION 14.96 • n=95 Participants	59.1 years STANDARD_DEVIATION 13.72 • n=96 Participants	58.6 years STANDARD_DEVIATION 14.33 • n=191 Participants
Sex: Female, Male Female	48 Participants n=95 Participants	44 Participants n=96 Participants	92 Participants n=191 Participants
Sex: Female, Male Male	47 Participants n=95 Participants	52 Participants n=96 Participants	99 Participants n=191 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=95 Participants	32 Participants n=96 Participants	60 Participants n=191 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants n=95 Participants	64 Participants n=96 Participants	130 Participants n=191 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=95 Participants	0 Participants n=96 Participants	1 Participants n=191 Participants
Race/Ethnicity, Customized White	68 Participants n=95 Participants	68 Participants n=96 Participants	136 Participants n=191 Participants
Race/Ethnicity, Customized Black or African American	11 Participants n=95 Participants	17 Participants n=96 Participants	28 Participants n=191 Participants
Race/Ethnicity, Customized Asian	4 Participants n=95 Participants	1 Participants n=96 Participants	5 Participants n=191 Participants
Race/Ethnicity, Customized America Indian or Alaska Native	1 Participants n=95 Participants	1 Participants n=96 Participants	2 Participants n=191 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=95 Participants	0 Participants n=96 Participants	1 Participants n=191 Participants
Race/Ethnicity, Customized Other	10 Participants n=95 Participants	9 Participants n=96 Participants	19 Participants n=191 Participants
Region of Enrollment United States	95 participants n=95 Participants	96 participants n=96 Participants	191 participants n=191 Participants

PRIMARY outcome

Timeframe: Through Day 28

Population: All Randomized Analysis Set

The number of subjects who died or had respiratory failure through Day 28

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=95 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=96 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
The Number of Subjects Who Died or Had Respiratory Failure	12 Participants	10 Participants

SECONDARY outcome

Timeframe: Through Day 28

Number of subjects to recover, where recover is defined as attaining a NIAID Ordinal score of 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen or 8) Not hospitalized, no limitations on activities sustained through Day 28, or discharge from hospital without re admission for COVID.

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=95 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=96 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Number of Subjects to Recover Recovered	61 Participants	70 Participants
Number of Subjects to Recover Not Recovered	34 Participants	26 Participants

SECONDARY outcome

Timeframe: Day 7

Population: All Randomized Analysis Set with NIAID scores at Day 7

The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=85 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=85 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale	5.28 score on a scale Standard Error 0.198	5.81 score on a scale Standard Error 0.192

SECONDARY outcome

Timeframe: Day 14

Population: All Randomized Analysis Set with NIAID scores at Day 14

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=59 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=61 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale	6.22 score on a scale Standard Error 0.208	6.38 score on a scale Standard Error 0.202

SECONDARY outcome

Timeframe: Day 28

Population: All Randomized Analysis Set with NIAID scores at Day 28

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=65 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=73 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale	6.56 score on a scale Standard Error 0.193	6.87 score on a scale Standard Error 0.186

SECONDARY outcome

Timeframe: Through Day 28

Population: (1) Discharged is defined as discharged alive from hospital through day 28. (2) For patients who were randomized but not treated, the date of randomization is used in place of the treatment start date.

Number of subjects discharged alive from hospital through Day 28

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=95 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=96 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Number of Subjects Discharged Alive From Hospital Discharged	89 Participants	88 Participants
Number of Subjects Discharged Alive From Hospital Not Discharged	6 Participants	7 Participants
Number of Subjects Discharged Alive From Hospital Missing Data	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Through Day 28

Population: (1) Subject hospital duration will be defined as the time from Day 1 (start of study treatment) to the day of hospital discharge or Day 28 of treatment for patients who are still hospitalized. If a patient has expired on or before Day 27 of treatment, they will be assigned a value of 28 days. (2) For patients who were randomized but not treated, the date of randomization is used in place of the treatment start date.

Duration of Hospitalization through Day 28

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=95 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=95 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Duration of Hospitalization	8.9 Days Standard Deviation 6.58	8.1 Days Standard Deviation 6.36

SECONDARY outcome

Timeframe: Through Day 28

All cause mortality through Day 28

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=95 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=96 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
All Cause Mortality	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Through Day 28

Population: Difference in converted RT-PCR Results at Discharge by Treatment Group. Only participants with a positive RT-PCR result at baseline are included in the analysis.

Proportion of subjects with a positive RT-PCR result at baseline from a nasopharyngeal swab through Day 28 reported as a proportion of positive or negative RT-PCR testing.

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=95 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=96 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Difference in Proportion in RT-PCR Results at Discharge by Treatment Group Positive RT-PCR Result	0.841 Proportion Converted Interval 0.751 to 0.932	0.812 Proportion Converted Interval 0.719 to 0.904
Difference in Proportion in RT-PCR Results at Discharge by Treatment Group Negative RT-PCR Result	0.159 Proportion Converted Interval 0.068 to 0.249	0.188 Proportion Converted Interval 0.096 to 0.281

OTHER_PRE_SPECIFIED outcome

Timeframe: Through Day 28

Population: Full Safety Set

Number of subjects with adverse events leading to study drug discontinuation through Day 28

Outcome measures

Outcome measures
Measure	Inhaled Nitric Oxide (iNO) n=91 Participants Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=95 Participants Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Number of Subjects With Adverse Events Leading to Study Drug Discontinuation	11 Participants	11 Participants

Adverse Events

Inhaled Nitric Oxide (iNO)

Serious events: 13 serious events

Other events: 16 other events

Deaths: 5 deaths

Placebo

Serious events: 12 serious events

Other events: 28 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Inhaled Nitric Oxide (iNO) n=91 participants at risk Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.	Placebo n=95 participants at risk Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
Respiratory, thoracic and mediastinal disorders Respiratory failure	7.7% 7/91 • Number of events 7 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	7.4% 7/95 • Number of events 7 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Respiratory, thoracic and mediastinal disorders Hypoxia	3.3% 3/91 • Number of events 3 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	3.2% 3/95 • Number of events 3 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.1% 1/91 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	0.00% 0/95 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.1% 1/91 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	0.00% 0/95 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Infections and infestations COVID-19 pneumonia	1.1% 1/91 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	0.00% 0/95 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Infections and infestations Septic Shock	1.1% 1/91 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	1.1% 1/95 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Infections and infestations Enterococcal bacteraemia	0.00% 0/91 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	1.1% 1/95 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Nervous system disorders Cerebral infarction	1.1% 1/91 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	0.00% 0/95 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Nervous system disorders Encephalopathy	1.1% 1/91 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	0.00% 0/95 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Nervous system disorders Generalised tonic-clonic seizure	1.1% 1/91 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	0.00% 0/95 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Nervous system disorders Hemianopia	1.1% 1/91 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	0.00% 0/95 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)
Injury, poisoning and procedural complications Transfusion reaction	0.00% 0/91 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)	1.1% 1/95 • Number of events 1 • Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)

Other adverse events

Additional Information

Bobae Kim

Bellerophon Therapeutics

Phone: (917) 675-2254

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place