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SARS (Severe Acute Respiratory Syndrome)Phase 2NOSARSCOVIDNCT04306393

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

A Phase 2 study testing Nitric Oxide Gas in people with SARS (Severe Acute Respiratory Syndrome) and Coronavirus, run by Massachusetts General Hospital at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Nitric Oxide Gas
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
5 sitesin 2 countries
Study dates
21 Mar 2020to 15 Jun 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Inclusion criteria: (1) Adult patients, >/= 18 year-old; (2) Patients admitted to the ICU; (3) Patients who are intubated and mechanically ventilated; (4) Confirmed diagnosis of SARS-CoV2 by positive rt-PCR.

Exclusion criteria: (1) Patients intubated for more than 72 hours from initiation of the treatment gas; (2) Subjects enrolled in another interventional research study; (3) Physician of record opposed to enrolling the patient due to perceived safety concerns; or any condition that does not allow the protocol to be followed safely; (4) Subjects with past medical history of lung malignancy or pneumonectomy or lung transplant; (5) Subjects receiving a tidal volume < 3 cc/kg of ideal body weight at the time of enrollment; (6) Subjects with severe burns involving more than 40% of Total Body Surface Area; (7) Subjects that have experienced cardiac arrest with CPR for longer than 30 minutes; (8) Subjects with a presumed severe deficit in cerebral function with fixed dilated pupil; (9) Subjects receiving renal replacement therapy at the time of enrollment; (10) Subjects who have an impaired ability to ventilate without assistance; (11) Subjects who have a history of malignancy or other irreversible disease/conditions with a 6-month mortality > 50%; (12) Subjects not fully committed to full support at the time of enrollment; (13) Subject receiving inhaled nitric oxide gas prior to enrollment; (14) Subject's hospital admission unrelated to COVID-19.

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

United States4 sites

  • University of Alabama

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Louisiana State University Health Shreveport

    Shreveport, Louisiana, 71103

Other trials in United States

Sweden1 site

  • Danderyd Sjukhus AB

    Danderyd, Stockholm County, 18288

Other trials in Sweden

About this study

Official title: Nitric Oxide Gas Inhalation Therapy for Mechanically Ventilated Patients With Severe Acute Respiratory Syndrome Caused by SARS-CoV2: a Randomized Clinical Trial.

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

Read the 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.

Being tested
Nitric Oxide Gas
Medical subject headings
Severe Acute Respiratory Syndrome, Coronavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nitric Oxide GasDrug

    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.

Study groups in NCT04306393
Study groupRoleWhat they receive
Treatment GroupExperimentalInhaled Nitric Oxide until PaO2/FiO2 >/= 300 mmHg
Receives: Drug: Nitric Oxide Gas
Control GroupNo interventionNot described

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 48 hours

Secondary outcomes (4)

  1. Time to Reach Normoxemia During the First 28 Days After Enrollment

    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".

    Measured: 28 days

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

    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."

    Measured: 28 days

  3. Survival at 28 Days From Enrollment

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

    Measured: 28 days

  4. Survival at 90 Days From Enrollment

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

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2020
  2. Study start21 Mar 2020
  3. Primary completion21 Dec 2021
  4. Study completion15 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04306393
Sponsor's protocol ID
NO-SARS-COVID-19
Acronym
NOSARSCOVID
Status last verified
Mar 2026
First submitted
10 Mar 2020
Last updated
1 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33783269

  • 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.

    PubMed 32511534

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nitric Oxide Gas in people with SARS (Severe Acute Respiratory Syndrome) and Coronavirus, run by Massachusetts General Hospital at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of Arterial Oxygenation at 48 Hours From Enrollment (time frame: 48 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04306393, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2026.

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