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Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID19 Infection (NoCovid)

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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Recruitment Status : Withdrawn (New coordinating center has been defined (Massachusetts General Hospital))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

Tracking Information
First Submitted Date  ICMJE February 27, 2020
First Posted Date  ICMJE March 2, 2020
Last Update Posted Date March 24, 2020
Estimated Study Start Date  ICMJE March 1, 2020
Estimated Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 9, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 28, 2020)
Reduction in the proportion of early stage patients [ Time Frame: 28 days ]
who progress to a severe form of the disease defined as: SpO2 < 93% without oxygen supplementation sustained for more than 12 hours; or, PaO2/FiO2 ratio < 300 mmHg sustained for more than 12 hours; or, necessity of high flow nasal cannula oxygen or intubation and mechanical ventilation or ECMO therapy.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2020)
  • Mortality [ Time Frame: 28 days ]
    Mortality 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 a nasopahryngeal 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) and alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent).
Original Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2020)
  • Mortality [ Time Frame: 28 days ]
    Mortality from all causes
  • Time to negative conversion of COVID-19 RT-PCR from upper respiratory tract [ Time Frame: 28 days ]
    Time to negative conversion of COVID-19 RT-PCR from upper respiratory tract
  • 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), with SpO2 or SaO2 >=93 % in ambient air . All of these improvements have to last for at least 72 hours.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nitric Oxide Gas Inhalation Therapy for Mild/Moderate COVID19 Infection
Official Title  ICMJE Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID19 Infection: 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 (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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronavirus Infections
  • Pneumonia, Viral
  • Dyspnea
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 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
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
    The control group will receive the standard of treatment without any active, placebo or sham Comparator.
Publications *

*   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 Withdrawn
Actual Enrollment  ICMJE
 (submitted: March 22, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: February 28, 2020)
400
Estimated Study Completion Date  ICMJE February 1, 2022
Estimated Primary Completion Date March 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.
  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
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 Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04290858
Other Study ID Numbers  ICMJE COVID19 NOgas mild
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party chonglei, Xijing Hospital
Study Sponsor  ICMJE Xijing Hospital
Collaborators  ICMJE Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Investigators  ICMJE
Principal Investigator: Lei Chong, MD, PhD Xijing Hospital
Principal Investigator: Lorenzo Berra, MD Massachusetts General Hospital
PRS Account Xijing Hospital
Verification Date March 2020

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