Trial Outcomes & Findings for Nitric Oxide Gas Inhalation in Severe Acute Respiratory Syndrome in COVID-19 (NCT NCT04306393)

Last Updated: 2026-04-01

Results Overview

Difference within groups in terms of PaO2/FiO2 ratio. If a patient dies during the first 48 hours of treatment, the last available blood gas analysis will be used.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

200 participants

Primary outcome timeframe

48 hours

Results posted on

2026-04-01

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Group Inhaled Nitric Oxide until PaO2/FiO2 \>/= 300 mmHg Nitric Oxide Gas: 80 ppm of inhaled nitric oxide for 48 hours, followed by 40 ppm, followed by weaning before stop. Weaning criteria: maintenance of a PaO2/FiO2 ratio \>/= 300 for at least 24 hours consecutively.	Control Group Institutional usual care
Overall Study STARTED	100	100
Overall Study COMPLETED	94	99
Overall Study NOT COMPLETED	6	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Nitric Oxide Gas Inhalation in Severe Acute Respiratory Syndrome in COVID-19

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Group n=94 Participants Inhaled Nitric Oxide until PaO2/FiO2 \>/= 300 mmHg Nitric Oxide Gas: 80 ppm of inhaled nitric oxide for 48 hours, followed by 40 ppm, followed by weaning before stop. Weaning criteria: maintenance of a PaO2/FiO2 ratio \>/= 300 for at least 24 hours consecutively.	Control Group n=99 Participants Institutional usual care	Total n=193 Participants Total of all reporting groups
Age, Continuous	64 years n=5 Participants	62 years n=5 Participants	63 years n=10 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	34 Participants n=5 Participants	65 Participants n=10 Participants
Sex: Female, Male Male	63 Participants n=5 Participants	65 Participants n=5 Participants	128 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants	30 Participants n=5 Participants	57 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants n=5 Participants	69 Participants n=5 Participants	136 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=5 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	7 Participants n=5 Participants	13 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	23 Participants n=5 Participants	20 Participants n=5 Participants	43 Participants n=10 Participants
Race (NIH/OMB) White	49 Participants n=5 Participants	61 Participants n=5 Participants	110 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	11 Participants n=5 Participants	26 Participants n=10 Participants
Smoking history Current Smoker	4 Participants n=5 Participants	6 Participants n=5 Participants	10 Participants n=10 Participants
Smoking history Former Smoker	25 Participants n=5 Participants	30 Participants n=5 Participants	55 Participants n=10 Participants
Smoking history Never Smoked	49 Participants n=5 Participants	42 Participants n=5 Participants	91 Participants n=10 Participants
Smoking history Unknown	16 Participants n=5 Participants	21 Participants n=5 Participants	37 Participants n=10 Participants
Hypertension	63 Participants n=5 Participants	46 Participants n=5 Participants	109 Participants n=10 Participants
BMI	31 kg/m^2 n=5 Participants	30.2 kg/m^2 n=5 Participants	30.5 kg/m^2 n=10 Participants
History of myocardial infarction	13 Participants n=5 Participants	11 Participants n=5 Participants	24 Participants n=10 Participants
Diabetes	39 Participants n=5 Participants	29 Participants n=5 Participants	68 Participants n=10 Participants
Cerebrovascular disease	5 Participants n=5 Participants	8 Participants n=5 Participants	13 Participants n=10 Participants
Chronic Kidney Disease	10 Participants n=5 Participants	8 Participants n=5 Participants	18 Participants n=10 Participants
COPD	4 Participants n=5 Participants	8 Participants n=5 Participants	12 Participants n=10 Participants
Connective Tissue disease	6 Participants n=5 Participants	1 Participants n=5 Participants	7 Participants n=10 Participants
Dementia	4 Participants n=5 Participants	3 Participants n=5 Participants	7 Participants n=10 Participants
Immune Deficiency	5 Participants n=5 Participants	3 Participants n=5 Participants	8 Participants n=10 Participants
Liver disease	8 Participants n=5 Participants	0 Participants n=5 Participants	8 Participants n=10 Participants
History of malignancy	7 Participants n=5 Participants	0 Participants n=5 Participants	7 Participants n=10 Participants
History of peptic ulcer	3 Participants n=5 Participants	4 Participants n=5 Participants	7 Participants n=10 Participants

PRIMARY outcome

Timeframe: 48 hours

Difference within groups in terms of PaO2/FiO2 ratio. If a patient dies during the first 48 hours of treatment, the last available blood gas analysis will be used.

Outcome measures

Outcome measures
Measure	Treatment Group n=94 Participants Inhaled Nitric Oxide until PaO2/FiO2 \>/= 300 mmHg Nitric Oxide Gas: 80 ppm of inhaled nitric oxide for 48 hours, followed by 40 ppm, followed by weaning before stop. Weaning criteria: maintenance of a PaO2/FiO2 ratio \>/= 300 for at least 24 hours consecutively.	Control Group n=99 Participants Institutional usual care
Change of Arterial Oxygenation at 48 Hours From Enrollment	200 ratio Interval 157.0 to 239.0	183 ratio Interval 122.0 to 235.0

SECONDARY outcome

Timeframe: 28 days

Time to recover gas exchange to a PaO2/FiO2 =/\> 300 for at least 24 hours during the first 28 days after enrollment, within each group and comparison between groups. If the patient dies before day 28, the patient will be considered as "never recovered".

Outcome measures

Outcome measures
Measure	Treatment Group n=94 Participants Inhaled Nitric Oxide until PaO2/FiO2 \>/= 300 mmHg Nitric Oxide Gas: 80 ppm of inhaled nitric oxide for 48 hours, followed by 40 ppm, followed by weaning before stop. Weaning criteria: maintenance of a PaO2/FiO2 ratio \>/= 300 for at least 24 hours consecutively.	Control Group n=99 Participants Institutional usual care
Time to Reach Normoxemia During the First 28 Days After Enrollment	8.7 days Standard Deviation 5	8.4 days Standard Deviation 6.5

SECONDARY outcome

Timeframe: 28 days

Proportion of patients in each group who achieved a PaO₂/FiO₂ ratio \>300 for at least 24 consecutive hours during the first 28 days after enrollment. Patients who died before day 28 were classified as "never recovered."

Outcome measures

Outcome measures
Measure	Treatment Group n=94 Participants Inhaled Nitric Oxide until PaO2/FiO2 \>/= 300 mmHg Nitric Oxide Gas: 80 ppm of inhaled nitric oxide for 48 hours, followed by 40 ppm, followed by weaning before stop. Weaning criteria: maintenance of a PaO2/FiO2 ratio \>/= 300 for at least 24 hours consecutively.	Control Group n=99 Participants Institutional usual care
Proportion of SARS-nCoV-2 Free Patients During the First 28 Days After Enrollment	33 Participants	21 Participants

SECONDARY outcome

Timeframe: 28 days

Proportion of patients surviving at 28 days within each group and comparison between groups.

Outcome measures

Outcome measures
Measure	Treatment Group n=94 Participants Inhaled Nitric Oxide until PaO2/FiO2 \>/= 300 mmHg Nitric Oxide Gas: 80 ppm of inhaled nitric oxide for 48 hours, followed by 40 ppm, followed by weaning before stop. Weaning criteria: maintenance of a PaO2/FiO2 ratio \>/= 300 for at least 24 hours consecutively.	Control Group n=99 Participants Institutional usual care
Survival at 28 Days From Enrollment	67 Participants	72 Participants

SECONDARY outcome

Timeframe: 90 days

Proportion of patients surviving at 90 days within each group and comparison between groups.

Outcome measures

Outcome measures
Measure	Treatment Group n=94 Participants Inhaled Nitric Oxide until PaO2/FiO2 \>/= 300 mmHg Nitric Oxide Gas: 80 ppm of inhaled nitric oxide for 48 hours, followed by 40 ppm, followed by weaning before stop. Weaning criteria: maintenance of a PaO2/FiO2 ratio \>/= 300 for at least 24 hours consecutively.	Control Group n=99 Participants Institutional usual care
Survival at 90 Days From Enrollment	62 Participants	67 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Expressed as PaO2/FiO2 ratio within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Proportion of patients needing RRT within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Proportion of patients needing mechanical support of circulation (i.e., ECMO, intra-aortic balloon pump, VADs) within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Average days without need for vasopressors within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Average days without need for mechanical ventilation within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Time to obtain first negative upper respiratory tract sample in the 2019-nCoV rt-PCR assay. Average within groups and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Average days out of ICU within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 90 days

Average days of ICU admission within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Number of copies of SARS-CoV-2 Viral Load measured with rt-PCR on sputum samples within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Number of copies of SARS-CoV-2 Viral Load measured with rt-PCR on blood samples within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Proportion of patients with acute kidney injury and severity of acute kidney injury within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Daily calculation of the vasoactive inotropic score in each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Proportion of patients requiring venous-venous extracorporeal membrane oxygenation within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Daily calculation of the sequential organ failure assessment within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Average days after hospital discharge within each group and comparison between groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 90 days

Average days of hospital stay within each group and comparison between groups.

Outcome measures

Outcome data not reported

Adverse Events

Treatment Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 32 deaths

Control Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 32 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Lorenzo Berra, MD

Massachusetts General Hospital

Phone: 617-726-3030

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place