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

NCT04306393 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NO-SARS-COVID-19
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 5

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

Conditions

SARS (Severe Acute Respiratory Syndrome); Coronavirus

Outcome Measures

Primary Outcomes (1)

• Change of Arterial Oxygenation at 48 Hours From Enrollment

  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.

  48 hours

Secondary Outcomes (4)

• Time to Reach Normoxemia During the First 28 Days After Enrollment

  28 days

• Proportion of SARS-nCoV-2 Free Patients During the First 28 Days After Enrollment

  28 days

• Survival at 28 Days From Enrollment

  28 days

• Survival at 90 Days From Enrollment

  90 days

Other Outcomes (16)

• Daily Oxygenation in the Two Groups Until Day 28

  28 days

• Need for New Renal Replacement Therapy During the First 28 Days

  28 days

• Mechanical Support of Circulation During the First 28 Days

  28 days

Study Arms (2)

Treatment Group

EXPERIMENTAL

Inhaled Nitric Oxide until PaO2/FiO2 \>/= 300 mmHg

Drug: Nitric Oxide Gas

Control Group

NO INTERVENTION

Interventions

Nitric Oxide Gas DRUG

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.

Treatment Group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Xijing Hospital: collaborator
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator
• Niguarda Hospital: collaborator

Study Sites (5)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Louisiana State University Health Shreveport

Shreveport, Louisiana, 71103, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Danderyd Sjukhus AB

Danderyd, Stockholm County, 18288, Sweden

Location

Related Publications (2)

• Gibson LE, Fenza RD, Lang M, Capriles MI, Li MD, Kalpathy-Cramer J, Little BP, Arora P, Mueller AL, Ichinose F, Bittner EA, Berra L, G Chang M. Right Ventricular Strain Is Common in Intubated COVID-19 Patients and Does Not Reflect Severity of Respiratory Illness. J Intensive Care Med. 2021 Aug;36(8):900-909. doi: 10.1177/08850666211006335. Epub 2021 Mar 30.

  PMID: 33783269 DERIVED

• Lei C, Su B, Dong H, Bellavia A, Fenza RD, Fakhr BS, Gianni S, Grassi LG, Kacmarek R, Morais CCA, Pinciroli R, Vassena E, Berra L. Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2). medRxiv [Preprint]. 2020 May 24:2020.03.09.20033530. doi: 10.1101/2020.03.09.20033530.

  PMID: 32511534 DERIVED

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; Coronavirus Infections

Interventions

Endothelium-Dependent Relaxing Factors

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Lorenzo Berra, MD
• Organization: Massachusetts General Hospital

lberra@mgh.harvard.edu

617-726-3030

Study Officials

• Lorenzo Berra, MD

  Massachusetts General Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The patient is blinded to the treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: March 12, 2020
• Study Start: March 21, 2020
• Primary Completion: December 21, 2021
• Study Completion: June 15, 2022
• Last Updated: April 1, 2026
• Results First Posted: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); SE (1)