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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04306393
Recruitment Status : Recruiting
First Posted : March 12, 2020
Last Update Posted : May 21, 2020
Sponsor:
Collaborators:
Xijing Hospital
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Niguarda Hospital
Information provided by (Responsible Party):
Lorenzo Berra, MD, 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

Condition or disease Intervention/treatment Phase
SARS (Severe Acute Respiratory Syndrome) Coronavirus Drug: Nitric Oxide Gas Phase 2

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.

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Study Type : Interventional
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: The patient is blinded to the treatment.
Primary Purpose: Treatment
Official Title: Nitric Oxide Gas Inhalation Therapy for Mechanically Ventilated Patients With Severe Acute Respiratory Syndrome Caused by SARS-CoV2: a Randomized Clinical Trial.
Actual Study Start Date : March 21, 2020
Estimated Primary Completion Date : March 21, 2021
Estimated Study Completion Date : March 21, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Group
Inhaled Nitric Oxide until PaO2/FiO2 >/= 300 mmHg
Drug: Nitric Oxide Gas

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.


No Intervention: Control Group



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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".

  2. 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".

  3. Survival at 28 days from enrollment [ Time Frame: 28 days ]
    Proportion of patients surviving at 28 days within each group and comparison between groups.

  4. Survival at 90 days from enrollment [ Time Frame: 90 days ]
    Proportion of patients surviving at 90 days within each group and comparison between groups.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. Mechanical support of circulation during the first 28 days [ Time Frame: 28 days ]
    Proportion of patients needing (i.e., ECMO, intra-aortic balloon pump, VADs) within each group and comparison between groups.

  4. 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.

  5. Ventilator-free day at 28 days [ Time Frame: 28 days ]
    Average days without need for mechanical ventilation within each group and comparison between groups.

  6. Time to SARS-CoV-2 rt-PCR negative in upper respiratory tract specimen [ Time Frame: 28 days ]
    Time to obtain first negative upper respiratory trait sample in the 2019-nCoV rt-PCR assay. Average within groups and comparison between groups.

  7. ICU-free days at 28 days [ Time Frame: 28 days ]
    Average days out of ICU within each group and comparison between groups.

  8. ICU length of stay [ Time Frame: 90 days ]
    Average days of ICU admission within each group and comparison between groups.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04306393


Contacts
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Contact: Lorenzo Berra, MD +16176437733 lberra@mgh.harvard.edu
Contact: Chong Lei, MD, PhD +8618629011362 crystalleichong@126.com

Locations
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United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
United States, Louisiana
Louisiana State University Health Shreveport Recruiting
Shreveport, Louisiana, United States, 71103
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Lorenzo Berra, MD         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Massachusetts General Hospital
Xijing Hospital
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Niguarda Hospital
Investigators
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Study Director: Lorenzo Berra, MD Massachusetts General Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Lorenzo Berra, MD, Medical Doctor, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04306393    
Other Study ID Numbers: NO-SARS-COVID-19
First Posted: March 12, 2020    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Syndrome
Disease
Pathologic Processes
Respiratory Tract Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents