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

Phase 2

Completed

• Conditions: Coronavirus; SARS (Severe Acute Respiratory Syndrome)
• Interventions: Drug: Nitric Oxide Gas

• Registration Number: NCT04306393
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

Severe acute respiratory syndrome (SARS-CoV2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used in as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In-vitro and clinical evidence indicate that inhaled nitric oxide gas (iNO) has also antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. This is a multicenter single-blinded randomized controlled trial with 1:1 individual allocation

Detailed Description

Severe acute respiratory syndrome (SARS-CoV-2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In has also shown in-vitro and clinical evidence that inhaled nitric oxide gas (iNO) has antiviral activity against other strains of coronavirus.

The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2.

This is a multicenter randomized controlled trial with 1:1 individual allocation. Patients will be blinded to the treatment.

Intubated patients admitted to the intensive care unit with confirmed SARS-CoV-2 infection and severe hypoxemia will be randomized to receive inhalation of NO (treatment group) or not (control group). Treatment will be stopped when patients are free from hypoxemia for more than 24 hours.

Study Timeline

• Study First Submitted: 2020-03-10
• Study First Submitted QC: 2020-03-10
• Study First Posted: 2020-03-12
• Study Start: 2020-03-21
• Primary Completion: 2021-12-21
• Status Verified: 2022-06
• Study Completion: 2022-06-15
• Last Update Submitted: 2022-06-20
• Last Update Posted: 2022-06-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group	Nitric Oxide Gas	Inhaled Nitric Oxide until PaO2/FiO2 \>/= 300 mmHg

Primary Outcome Measures

Name	Time	Method
Change of arterial oxygenation at 48 hours from enrollment	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.

Secondary Outcome Measures

Name	Time	Method
Time to reach normoxemia during the first 28 days after enrollment	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".
Proportion of SARS-nCoV-2 free patients during the first 28 days after enrollment	28 days	Daily proportion of patients with a PaO2/FiO2 ratio \> 300 for at least 24 hours within each group and comparison between groups. If a patient dies before day 28, the patient will be considered as "never recovered".
Survival at 28 days from enrollment	28 days	Proportion of patients surviving at 28 days within each group and comparison between groups.
Survival at 90 days from enrollment	90 days	Proportion of patients surviving at 90 days within each group and comparison between groups.

Trial Locations

Locations (5)

Danderyd Sjukhus AB; 🇸🇪 Danderyd, Stockholm, Sweden

Louisiana State University Health Shreveport; 🇺🇸 Shreveport, Louisiana, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States