Trial Outcomes & Findings for Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19 (NCT NCT04305457)
NCT ID: NCT04305457
Last Updated: 2026-03-23
Results Overview
The primary outcome will be the number of participants requiring intubation and mechanical ventilation, as a marker of deterioration from a mild to a severe form of COVID-19. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
62 participants
Primary outcome timeframe
28 days
Results posted on
2026-03-23
Participant Flow
Participant milestones
| Measure |
Nitric Oxide Inhalation
Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system.
Nitric Oxide: Nitric Oxide (NO) will be delivered together with the standard of care for a period of 20-30 minutes 2 times per day for 14 consecutive days from time of enrollment. Targeted No inhaled concentration will be maintained between 140 and 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or through a non-rebreathing mask without positive end-expiratory pressure, depending on the clinical needs of the subject.
|
Control
Patients assigned to the control group will not receive any gas therapy.
|
|---|---|---|
|
Overall Study
STARTED
|
29
|
33
|
|
Overall Study
COMPLETED
|
29
|
33
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19
Baseline characteristics by cohort
| Measure |
Nitric Oxide Inhalation
n=29 Participants
Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system.
Nitric Oxide: Nitric Oxide (NO) will be delivered together with the standard of care for a period of 20-30 minutes 2 times per day for 14 consecutive days from time of enrollment. Targeted No inhaled concentration will be maintained between 140 and 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or through a non-rebreathing mask without positive end-expiratory pressure, depending on the clinical needs of the subject.
|
Control
n=33 Participants
Patients assigned to the control group will not receive any gas therapy.
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50 years
n=10 Participants
|
50 years
n=8 Participants
|
50 years
n=18 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=10 Participants
|
15 Participants
n=8 Participants
|
28 Participants
n=18 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=10 Participants
|
18 Participants
n=8 Participants
|
34 Participants
n=18 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
22 Participants
n=10 Participants
|
22 Participants
n=8 Participants
|
44 Participants
n=18 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=10 Participants
|
11 Participants
n=8 Participants
|
18 Participants
n=18 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=18 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=10 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=18 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=10 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=18 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=10 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=18 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=10 Participants
|
3 Participants
n=8 Participants
|
5 Participants
n=18 Participants
|
|
Race (NIH/OMB)
White
|
27 Participants
n=10 Participants
|
30 Participants
n=8 Participants
|
57 Participants
n=18 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=10 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=18 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=18 Participants
|
|
Region of Enrollment
United States
|
29 participants
n=10 Participants
|
33 participants
n=8 Participants
|
62 participants
n=18 Participants
|
|
Comorbidities
Hypertension
|
12 participants
n=10 Participants
|
14 participants
n=8 Participants
|
26 participants
n=18 Participants
|
|
Comorbidities
Diabetes
|
10 participants
n=10 Participants
|
14 participants
n=8 Participants
|
24 participants
n=18 Participants
|
|
Comorbidities
Chronic Pulmonary Disease
|
3 participants
n=10 Participants
|
4 participants
n=8 Participants
|
7 participants
n=18 Participants
|
|
Comorbidities
None
|
10 participants
n=10 Participants
|
9 participants
n=8 Participants
|
19 participants
n=18 Participants
|
|
Comorbidities
Coronary Heart Disease
|
1 participants
n=10 Participants
|
1 participants
n=8 Participants
|
2 participants
n=18 Participants
|
|
Comorbidities
Malignancy
|
0 participants
n=10 Participants
|
1 participants
n=8 Participants
|
1 participants
n=18 Participants
|
|
Comorbidities
Cerebrovascular Disease
|
0 participants
n=10 Participants
|
1 participants
n=8 Participants
|
1 participants
n=18 Participants
|
|
Comorbidities
Chronic Kidney Disease
|
2 participants
n=10 Participants
|
3 participants
n=8 Participants
|
5 participants
n=18 Participants
|
|
Comorbidities
Immune Deficiency
|
1 participants
n=10 Participants
|
1 participants
n=8 Participants
|
2 participants
n=18 Participants
|
|
Comorbidities
Other
|
5 participants
n=10 Participants
|
2 participants
n=8 Participants
|
7 participants
n=18 Participants
|
PRIMARY outcome
Timeframe: 28 daysThe primary outcome will be the number of participants requiring intubation and mechanical ventilation, as a marker of deterioration from a mild to a severe form of COVID-19. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.
Outcome measures
| Measure |
Nitric Oxide Inhalation
n=29 Participants
Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system.
Nitric Oxide: Nitric Oxide (NO) will be delivered together with the standard of care for a period of 20-30 minutes 2 times per day for 14 consecutive days from time of enrollment. Targeted No inhaled concentration will be maintained between 140 and 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or through a non-rebreathing mask without positive end-expiratory pressure, depending on the clinical needs of the subject.
|
Control
n=33 Participants
Patients assigned to the control group will not receive any gas therapy.
|
|---|---|---|
|
Number of Participants With Mild/Moderate COVID-19 Requiring Intubation and Mechanical Ventilation
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 28 daysProportion of deaths from all causes
Outcome measures
| Measure |
Nitric Oxide Inhalation
n=29 Participants
Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system.
Nitric Oxide: Nitric Oxide (NO) will be delivered together with the standard of care for a period of 20-30 minutes 2 times per day for 14 consecutive days from time of enrollment. Targeted No inhaled concentration will be maintained between 140 and 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or through a non-rebreathing mask without positive end-expiratory pressure, depending on the clinical needs of the subject.
|
Control
n=33 Participants
Patients assigned to the control group will not receive any gas therapy.
|
|---|---|---|
|
Mortality
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 28 daysTime from initiation of the study to discharge or to normalization of fever (defined as \<36.6°C from axillary site, or \< 37.2°C from oral site or \< 37.8°C from rectal or tympanic site), respiratory rate (\< 24 bpm while breathing room air), alleviation of cough (defined as mild or absent in a patient reported scale of severe \>\>moderate\>\>mild\>\>absent) and resolution of hypoxia (defined as SpO2 ≥ 93% in room air or P/F ≥ 300 mmHg). All these improvements must be sustained for 72 hours.
Outcome measures
| Measure |
Nitric Oxide Inhalation
n=29 Participants
Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system.
Nitric Oxide: Nitric Oxide (NO) will be delivered together with the standard of care for a period of 20-30 minutes 2 times per day for 14 consecutive days from time of enrollment. Targeted No inhaled concentration will be maintained between 140 and 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or through a non-rebreathing mask without positive end-expiratory pressure, depending on the clinical needs of the subject.
|
Control
n=33 Participants
Patients assigned to the control group will not receive any gas therapy.
|
|---|---|---|
|
Time to Clinical Recovery
|
6 days
Interval 4.0 to 8.0
|
6 days
Interval 5.0 to 9.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 7 daysProportion of patients with a negative conversion of RT-PCR from an oropharyngeal or oropharyngeal swab.
Outcome measures
Outcome data not reported
Adverse Events
Nitric Oxide Inhalation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Control
Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place