- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04306393
Nitric Oxide Gas Inhalation in Severe Acute Respiratory Syndrome in COVID-19 (NOSARSCOVID)
Nitric Oxide Gas Inhalation Therapy for Mechanically Ventilated Patients With Severe Acute Respiratory Syndrome Caused by SARS-CoV2: a Randomized Clinical Trial.
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Stockholm
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Danderyd, Stockholm, Sweden, 18288
- Danderyd sjukhus AB
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-
-
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama
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Louisiana
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Shreveport, Louisiana, United States, 71103
- Louisiana State University Health Shreveport
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Control Group
|
|
Experimental: Treatment Group
Inhaled Nitric Oxide until PaO2/FiO2 >/= 300 mmHg
|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of arterial oxygenation at 48 hours from enrollment
Time Frame: 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.
|
48 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to reach normoxemia during the first 28 days after enrollment
Time Frame: 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".
|
28 days
|
Proportion of SARS-nCoV-2 free patients during the first 28 days after enrollment
Time Frame: 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".
|
28 days
|
Survival at 28 days from enrollment
Time Frame: 28 days
|
Proportion of patients surviving at 28 days within each group and comparison between groups.
|
28 days
|
Survival at 90 days from enrollment
Time Frame: 90 days
|
Proportion of patients surviving at 90 days within each group and comparison between groups.
|
90 days
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Daily oxygenation in the two groups until day 28
Time Frame: 28 days
|
Expressed as PaO2/FiO2 ratio within each group and comparison between groups.
|
28 days
|
Need for new renal replacement therapy during the first 28 days
Time Frame: 28 days
|
Proportion of patients needing RRT within each group and comparison between groups.
|
28 days
|
Mechanical support of circulation during the first 28 days
Time Frame: 28 days
|
Proportion of patients needing mechanical support of circulation (i.e., ECMO, intra-aortic balloon pump, VADs) within each group and comparison between groups.
|
28 days
|
Days free of vasopressors during the first 28 days
Time Frame: 28 days
|
Average days without need for vasopressors within each group and comparison between groups.
|
28 days
|
Ventilator-free days at 28 days
Time Frame: 28 days
|
Average days without need for mechanical ventilation within each group and comparison between groups.
|
28 days
|
Time to SARS-CoV-2 rt-PCR negative in upper respiratory tract specimen
Time Frame: 28 days
|
Time to obtain first negative upper respiratory tract sample in the 2019-nCoV rt-PCR assay.
Average within groups and comparison between groups.
|
28 days
|
ICU-free days at 28 days
Time Frame: 28 days
|
Average days out of ICU within each group and comparison between groups.
|
28 days
|
ICU length of stay
Time Frame: 90 days
|
Average days of ICU admission within each group and comparison between groups.
|
90 days
|
SARS-CoV-2 Viral Load in Sputum
Time Frame: 28 days
|
Number of copies of SARS-CoV-2 Viral Load measured with rt-PCR on sputum samples within each group and comparison between groups.
|
28 days
|
SARS-CoV-2 Viral Load in Plasma
Time Frame: 28 days
|
Number of copies of SARS-CoV-2 Viral Load measured with rt-PCR on blood samples within each group and comparison between groups.
|
28 days
|
Acute Kidney Injury at 28 days
Time Frame: 28 days
|
Proportion of patients with acute kidney injury and severity of acute kidney injury within each group and comparison between groups.
|
28 days
|
Daily Vasoactive Inotropic Score
Time Frame: 28 days
|
Daily calculation of the vasoactive inotropic score in each group and comparison between groups.
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28 days
|
Requirement for VV-ECMO
Time Frame: 28 days
|
Proportion of patients requiring venous-venous extracorporeal membrane oxygenation within each group and comparison between groups.
|
28 days
|
Daily Sequential Organ Failure Assessment
Time Frame: 28 days
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Daily calculation of the sequential organ failure assessment within each group and comparison between groups.
|
28 days
|
Hospital-free days at 28 days
Time Frame: 28 days
|
Average days after hospital discharge within each group and comparison between groups.
|
28 days
|
Hospital length of stay
Time Frame: 90 days
|
Average days of hospital stay within each group and comparison between groups.
|
90 days
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Lorenzo Berra, MD, Massachusetts General Hospital
Publications and helpful links
General 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.
- Lei C, Su B, Dong H, Bellavia A, Di Fenza R, Safaee Fakhr B, Gianni S, Grassi LG, Kacmarek R, Araujo Morais CC, 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. 2020 Mar 13:2020.03.09.20033530. doi: 10.1101/2020.03.09.20033530. Preprint.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Disease
- Severe Acute Respiratory Syndrome
- Syndrome
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Protective Agents
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Antioxidants
- Free Radical Scavengers
- Endothelium-Dependent Relaxing Factors
- Gasotransmitters
- Nitric Oxide
Other Study ID Numbers
- NO-SARS-COVID-19
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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