Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19

NCT ID: NCT04305457

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-21
• Study Completion Date: 2023-08-23

Brief Summary

The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (SARS-Cov-2) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on SARS-CoV-2 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.

Detailed Description

To date, no targeted therapeutic treatments for the ongoing COVID-19 outbreak have been identified. Antiviral combined with adjuvant therapies are currently under investigation. The clinical spectrum of the infection is wide, ranging from mild signs of upper respiratory tract infection to severe pneumonia and death.

In the patients who progress, the time period from symptoms onset to development of dyspnea is reported to be between 5 to 10 days, and that one to severe respiratory distress syndrome from 10 to 14 days. Globally, 15 to 18% of patients deteriorates to the need of mechanical ventilation, despite the use of non-invasive ventilatory support in the earliest phases of the disease. Probability of progression to end stage disease is unpredictable, with the majority of these patients dying from multi-organ failure. Preventing progression in spontaneously breathing patients with mild to moderate disease would translate in improved morbidity and mortality and in a lower use of limited healthcare resources.

In 2004, during the SARS-coronavirus (SARS-CoV) outbreak, a pilot study showed that low dose ( max 30 ppm) inhaled NO for 3 days was able to shorten the time of ventilatory support. At the same time, NO donor compound S-nitroso-N-acetylpenicillamine increased survival rate in an in-vitro model of SARS-CoV infected epithelial cells.Based on the genetic similarities between the two viruses, similar effects of NO on SARS-CoV-2 can be hypothesized. While further in-vitro testing is recommended, we proposed a randomized clinical trial to test the effectiveness of inhaled NO in preventing the progression of SARS-CoV-2 related disease, when administered at an early stage.

Conditions

Coronavirus Infections; Pneumonia, Viral; Acute Respiratory Distress Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Nitric Oxide

Intervention Type: DRUG

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Nitric Oxide Inhalation (Non-Randomized)

All subjects part of this arm will receive nitric oxide gas either as an inpatient or outpatient. 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. Patients in this arm will not be randomized, so that all patients receive the study medication.

Group Type: EXPERIMENTAL

Nitric Oxide

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Nitric Oxide inhalation

Eligibility Criteria

Inclusion Criteria

1. Laboratory confirmed COVID19 infection defined with a positive RT-PCR from any specimen and/or detection of SARS-CoV-2 IgM/IgG antibodies.

2. Hospital admission with at least one of the following:

1. fever ≥ 36.6 °C from axillary site; or ≥ 37.2°C from oral site; or ≥ 37.6°C from tympanic or rectal site.

2. Respiratory rate ≥ 24 bpm

3. cough

3. Spontaneous breathing with or without hypoxia of any degree. Gas exchange and ventilation maybe assisted by any continuous continuous airway pressure (CPAP), or any system of Non Invasive Ventilation (NIV), with Positive End-Expiratory Pressure (PEEP) ≤ 10 cmH2O.

Exclusion Criteria

1. Tracheostomy

2. Therapy with high flow nasal cannula

3. Any clinical contraindications, as judged by the attending physician

4. Patients enrolled in another interventional study

5. Hospitalized and confirmed diagnosis of COVID-19 for more than 72 hours

6. Previous intubation for COVID-19

7. Patient not committed to full support (DNR, DNI or CMO)

8. Patient requiring oxygen at home for lung comorbidities

9. Primary cause of hopitalization not due to COVID-19

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lorenzo Berra, MD

Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lorenzo Berra, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Providence HealthCare Network

Anchorage, Alaska, United States

Louisiana State University Health Shreveport

Shreveport, Louisiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

NOgas mildCOVID-19

Identifier Type: -

Identifier Source: org_study_id