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Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID19 Infection (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: NCT04290858
Recruitment Status : Withdrawn (New coordinating center has been defined (Massachusetts General Hospital))
First Posted : March 2, 2020
Last Update Posted : March 24, 2020
Sponsor:
Collaborator:
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Information provided by (Responsible Party):
chonglei, Xijing Hospital

Brief Summary:
The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (COVID-19) 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 COVID-19 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.

Condition or disease Intervention/treatment Phase
Coronavirus Infections Pneumonia, Viral Dyspnea Drug: Nitric Oxide Phase 2

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 progress 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 morbility 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 eukaryotic cells.Based on the genetic similarities between the two viruses, similar effects of NO on COVID-19 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 COVID-19 related disease, when administered at an early stage.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID19 Infection: a Randomized Clinical Trial
Estimated Study Start Date : March 1, 2020
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : February 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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 concentration will have a tidal oscillation between 100 and 300 ppm, in order to maintain an average inhaled concentration from 140 to 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or trough a non-rebreathing mask without positive end expiratory pressure, depending on the clinical needs of the patient.
Other Name: Nitric Oxide inhalation

No Intervention: Control
The control group will receive the standard of treatment without any active, placebo or sham Comparator.



Primary Outcome Measures :
  1. Reduction in the incidence of intubation and mechanical ventilation [ Time Frame: 28 days ]
    The primary outcome will be the proportion of patients with mild COVID2019 who deteriorate to a severe form of the disease requiring intubation and mechanical ventilation. 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 :
  1. Mortality [ Time Frame: 28 days ]
    Mortality from all causes

  2. 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 a nasopahryngeal swab

  3. 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) and alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent).



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Laboratory confirmed COVID19 infection defined with a positive RT-PCR from any specimen.
  2. 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
  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.
  4. ≤ 8 days since onset of the symptoms

Exclusion Criteria:

  1. Pregnancy, or positive pregnancy test in a predose examination
  2. Open tracheostomy
  3. Therapy with high flow nasal cannula
  4. Clinical controindication, as deemed by the attending physician

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): NCT04290858


Sponsors and Collaborators
Xijing Hospital
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Investigators
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Principal Investigator: Lei Chong, MD, PhD Xijing Hospital
Principal Investigator: Lorenzo Berra, MD Massachusetts General Hospital
Publications:
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Responsible Party: chonglei, M.D. & Ph.D., Xijing Hospital
ClinicalTrials.gov Identifier: NCT04290858    
Other Study ID Numbers: COVID19 NOgas mild
First Posted: March 2, 2020    Key Record Dates
Last Update Posted: March 24, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by chonglei, Xijing Hospital:
COVID-19
Pneumonia
dyspnea
Non-invasive ventilation
Respiratory failure
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia, Viral
Pneumonia
Dyspnea
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Respiration Disorders
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
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