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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04305457
Recruitment Status : Active, not recruiting
First Posted : March 12, 2020
Last Update Posted : December 29, 2020
Sponsor:
Collaborator:
University of Alabama at Birmingham
Information provided by (Responsible Party):
Lorenzo Berra, MD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE March 9, 2020
First Posted Date  ICMJE March 12, 2020
Last Update Posted Date December 29, 2020
Actual Study Start Date  ICMJE March 21, 2020
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2020)
Reduction in the incidence of patients with mild/moderate COVID-19 requiring intubation and mechanical ventilation [ Time Frame: 28 days ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2020)
  • Mortality [ Time Frame: 28 days ]
    Proportion of deaths from all causes
  • Time to clinical recovery [ Time Frame: 28 days ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2020)
  • Mortality [ Time Frame: 28 days ]
    Proportion of deaths from all causes
  • Negative conversion of COVID-19 RT-PCR from upper respiratory tract [ Time Frame: 7 days ]
    Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or oropharyngeal swab.
  • Time to clinical recovery [ Time Frame: 28 days ]
    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.
Current Other Pre-specified Outcome Measures
 (submitted: March 17, 2020)
Negative conversion of COVID-19 RT-PCR from upper respiratory tract [ Time Frame: 7 days ]
Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or oropharyngeal swab.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID-19
Official Title  ICMJE Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID-19: a Randomized Clinical Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronavirus Infections
  • Pneumonia, Viral
  • Acute Respiratory Distress Syndrome
Intervention  ICMJE Drug: Nitric Oxide
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.
Other Name: Nitric Oxide inhalation
Study Arms  ICMJE
  • Experimental: Nitric Oxide inhalation
    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.
    Intervention: Drug: Nitric Oxide
  • No Intervention: Control
    Patients assigned to the control group will not receive any gas therapy.
  • Experimental: Nitric Oxide Inhalation (Non-Randomized)
    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: Drug: Nitric Oxide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 15, 2020)
70
Original Estimated Enrollment  ICMJE
 (submitted: March 11, 2020)
240
Estimated Study Completion Date  ICMJE April 1, 2022
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04305457
Other Study ID Numbers  ICMJE NOgas mildCOVID-19
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Lorenzo Berra, MD, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE University of Alabama at Birmingham
Investigators  ICMJE
Principal Investigator: Lorenzo Berra, MD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP