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Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19 (NoCovid)

Primary Purpose

Coronavirus Infections, Pneumonia, Viral, Acute Respiratory Distress Syndrome

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nitric Oxide
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronavirus Infections focused on measuring COVID-19, ARDS, Mechanical Ventilation, Nitric Oxide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Laboratory confirmed COVID19 infection defined with a positive RT-PCR from any specimen and/or detection of SARS-CoV-2 IgM/IgG antibodies.
  2. Hospital admission with at least one of the following:

    1. fever ≥ 36.6 °C from axillary site; or ≥ 37.2°C from oral site; or ≥ 37.6°C from tympanic or rectal site.
    2. Respiratory rate ≥ 24 bpm
    3. cough
  3. Spontaneous breathing with or without hypoxia of any degree. Gas exchange and ventilation maybe assisted by any continuous continuous airway pressure (CPAP), or any system of Non Invasive Ventilation (NIV), with Positive End-Expiratory Pressure (PEEP) ≤ 10 cmH2O.

Exclusion Criteria:

  1. Tracheostomy
  2. Therapy with high flow nasal cannula
  3. Any clinical contraindications, as judged by the attending physician
  4. Patients enrolled in another interventional study
  5. Hospitalized and confirmed diagnosis of COVID-19 for more than 72 hours
  6. Previous intubation for COVID-19
  7. Patient not committed to full support (DNR, DNI or CMO)
  8. Patient requiring oxygen at home for lung comorbidities
  9. Primary cause of hopitalization not due to COVID-19

Sites / Locations

  • Providence HealthCare Network
  • Louisiana State University Health Shreveport
  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

Experimental

Arm Label

Nitric Oxide inhalation

Control

Nitric Oxide Inhalation (Non-Randomized)

Arm Description

Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system.

Patients assigned to the control group will not receive any gas therapy.

All subjects part of this arm will receive nitric oxide gas either as an inpatient or outpatient. Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system. Patients in this arm will not be randomized, so that all patients receive the study medication.

Outcomes

Primary Outcome Measures

Reduction in the incidence of patients with mild/moderate COVID-19 requiring intubation and mechanical ventilation
The primary outcome will be the reduction in the incidence of patients requiring intubation and mechanical ventilation, as a marker of deterioration from a mild to a severe form of COVID-19. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.

Secondary Outcome Measures

Mortality
Proportion of deaths from all causes
Time to clinical recovery
Time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air), alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent) and resolution of hypoxia (defined as SpO2 ≥ 93% in room air or P/F ≥ 300 mmHg). All these improvements must be sustained for 72 hours.

Full Information

First Posted
March 9, 2020
Last Updated
October 31, 2022
Sponsor
Massachusetts General Hospital
Collaborators
University of Alabama at Birmingham
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1. Study Identification

Unique Protocol Identification Number
NCT04305457
Brief Title
Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19
Acronym
NoCovid
Official Title
Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID-19: a Randomized Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 21, 2020 (Actual)
Primary Completion Date
April 2025 (Anticipated)
Study Completion Date
April 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
University of Alabama at Birmingham

4. Oversight

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

5. Study Description

Brief Summary
The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (SARS-Cov-2) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on SARS-CoV-2 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.
Detailed Description
To date, no targeted therapeutic treatments for the ongoing COVID-19 outbreak have been identified. Antiviral combined with adjuvant therapies are currently under investigation. The clinical spectrum of the infection is wide, ranging from mild signs of upper respiratory tract infection to severe pneumonia and death. In the patients who progress, the time period from symptoms onset to development of dyspnea is reported to be between 5 to 10 days, and that one to severe respiratory distress syndrome from 10 to 14 days. Globally, 15 to 18% of patients deteriorates to the need of mechanical ventilation, despite the use of non-invasive ventilatory support in the earliest phases of the disease. Probability of progression to end stage disease is unpredictable, with the majority of these patients dying from multi-organ failure. Preventing progression in spontaneously breathing patients with mild to moderate disease would translate in improved morbidity and mortality and in a lower use of limited healthcare resources. In 2004, during the SARS-coronavirus (SARS-CoV) outbreak, a pilot study showed that low dose ( max 30 ppm) inhaled NO for 3 days was able to shorten the time of ventilatory support. At the same time, NO donor compound S-nitroso-N-acetylpenicillamine increased survival rate in an in-vitro model of SARS-CoV infected epithelial cells.Based on the genetic similarities between the two viruses, similar effects of NO on SARS-CoV-2 can be hypothesized. While further in-vitro testing is recommended, we proposed a randomized clinical trial to test the effectiveness of inhaled NO in preventing the progression of SARS-CoV-2 related disease, when administered at an early stage.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Infections, Pneumonia, Viral, Acute Respiratory Distress Syndrome
Keywords
COVID-19, ARDS, Mechanical Ventilation, Nitric Oxide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This study includes a randomized, parallel arm clinical trial in which subjects will be randomized to receive either inhaled nitric oxide (in addition to the standard of care) or the standard of care alone. In a third arm, COVID-19 subjects will be enrolled at Providence HealthCare Network, Anchorage (AK). Subjects in this arm will not be randomized and will all receive nitric oxide gas either as an inpatient or outpatient.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nitric Oxide inhalation
Arm Type
Experimental
Arm Description
Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Patients assigned to the control group will not receive any gas therapy.
Arm Title
Nitric Oxide Inhalation (Non-Randomized)
Arm Type
Experimental
Arm Description
All subjects part of this arm will receive nitric oxide gas either as an inpatient or outpatient. Nitric Oxide will be delivered through a non invasive CPAP system (with minimal pressure support to decrease discomfort due to the facial mask) or through a non-rebreathing mask system. Patients in this arm will not be randomized, so that all patients receive the study medication.
Intervention Type
Drug
Intervention Name(s)
Nitric Oxide
Other Intervention Name(s)
Nitric Oxide inhalation
Intervention Description
Nitric Oxide (NO) will be delivered together with the standard of care for a period of 20-30 minutes 2 times per day for 14 consecutive days from time of enrollment. Targeted No inhaled concentration will be maintained between 140 and 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or through a non-rebreathing mask without positive end-expiratory pressure, depending on the clinical needs of the subject.
Primary Outcome Measure Information:
Title
Reduction in the incidence of patients with mild/moderate COVID-19 requiring intubation and mechanical ventilation
Description
The primary outcome will be the reduction in the incidence of patients requiring intubation and mechanical ventilation, as a marker of deterioration from a mild to a severe form of COVID-19. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Mortality
Description
Proportion of deaths from all causes
Time Frame
28 days
Title
Time to clinical recovery
Description
Time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air), alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent) and resolution of hypoxia (defined as SpO2 ≥ 93% in room air or P/F ≥ 300 mmHg). All these improvements must be sustained for 72 hours.
Time Frame
28 days
Other Pre-specified Outcome Measures:
Title
Negative conversion of COVID-19 RT-PCR from upper respiratory tract
Description
Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or oropharyngeal swab.
Time Frame
7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Laboratory confirmed COVID19 infection defined with a positive RT-PCR from any specimen and/or detection of SARS-CoV-2 IgM/IgG antibodies. Hospital admission with at least one of the following: fever ≥ 36.6 °C from axillary site; or ≥ 37.2°C from oral site; or ≥ 37.6°C from tympanic or rectal site. Respiratory rate ≥ 24 bpm cough Spontaneous breathing with or without hypoxia of any degree. Gas exchange and ventilation maybe assisted by any continuous continuous airway pressure (CPAP), or any system of Non Invasive Ventilation (NIV), with Positive End-Expiratory Pressure (PEEP) ≤ 10 cmH2O. Exclusion Criteria: Tracheostomy Therapy with high flow nasal cannula Any clinical contraindications, as judged by the attending physician Patients enrolled in another interventional study Hospitalized and confirmed diagnosis of COVID-19 for more than 72 hours Previous intubation for COVID-19 Patient not committed to full support (DNR, DNI or CMO) Patient requiring oxygen at home for lung comorbidities Primary cause of hopitalization not due to COVID-19
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorenzo Berra, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Providence HealthCare Network
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99508
Country
United States
Facility Name
Louisiana State University Health Shreveport
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114-2621
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19

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