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

February 5, 2023 updated by: Chong Lei, MD & phD, Xijing Hospital

Nitric Oxide Gas Inhalation Therapy for Severe Acute Respiratory Syndrome Due to COVID-19.

The investigators will enroll 104 patients with severe COVID-19 infection that mechanical ventilation is needed for respiratory support. Patients will be randomized to receive either inhaled nitric oxide (per protocol) or a placebo. ICU Standards of care will be the institution's own protocols (such as ventilation strategies and use and dose of antivirals and antimicrobials, steroids, inotropic and vasopressor agents).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The outbreak of COVID-19 and its global pandemic have posed a threat to public health. The deadly virus, SARS-CoV-2, has been evolving to new, more infectious variant and other lineages with additional immune escape mutations. The highly transmissible Omicron variant has been present for around one year and has supplanted Delta as the leading strain in the global pandemic. Although the severity of symptoms caused by the Omicron variant is significantly reduced when compared to its earlier variants, people who are infected with Omicron have the full spectrum of disease, everything from asymptomatic infection all the way through severe disease and death. People with underlying conditions, advanced age, and unvaccinated can have a severe form of COVID-19 following infection from Omicron. On December 7, 2022, the State Council of China issued an announcement on further optimization of measures for preventing and controlling the COVID-19 epidemic ( easing of rigorous "zero COVID" policies). Since then, the rapid spread of COVID-19 has caused surge of COVID-19 infections in majority of China, which caused a dramatic increase of severe cases.

In severe cases with COVID-19 infection significantly affects the respiratory functions by massively disrupting the pulmonary oxygenation and activating the synthesis of proinflammatory cytokines, inducing severe oxidative stress, enhanced vascular permeability, and endothelial dysfunction which have rendered researchers and clinicians to depend on prophylactic treatment due to the unavailability of proper disease management approaches. Inhaled nitric oxide gas (NO) has shown antiviral activity against Coronavirus during the 2003 SARS outbreak. Previous studies have indicated that nitric oxide (NO) application appears to be significant concerning the antiviral activities, antioxidant, and anti-inflammatory properties in relieving disease-related symptoms. Inhaled nitric oxide had been widely used during the Covid-19 pandemic. In the scoping and systemic reviews, it was demonstrated that nitric oxide inhalation was effective in improve oxygenation, cardiopulmonary function, and fasten virus clearance. The investigators designed this study to assess whether inhaled NO improves respiratory recovery in patients affected with severe COVID-19 infection.

Here, the investigators propose a randomized clinical trial aimed to improve recovery of the disease in patients with severe acute respiratory syndrome.

Control group: the institutional standard of care will be delivered. Treatment group: In addition to standard therapy, the subjects will receive inhalation of NO. Inspired NO/N2 will be delivered at 80 parts per million (ppm) in the first 48 hours of enrollment (within 48 hours after initiation of mechanical ventilation). Weaning from NO will start after 48-h consecutive NO inhalation. Physician will follow their own institutional weaning protocols. In the absence of institutional protocols, NO will be reduced every 4 hours in step-wise fashion starting from 40 ppm to 20, 10, 5, 3, 2 and 1 ppm. If hypoxemia (SpO2 < 93%) or acute hypotension (systolic blood pressure < 90 mmHg) occurs during weaning, NO should be increased to a prior higher concentration.

Safety: prolonged treatment with inhaled NO can lead to increased methemoglobin levels. Blood levels of methemoglobin will be monitored via a non-invasive CO-oximeter or MetHb levels in blood. If methemoglobin levels rise above 5% at any point of the study, inhaled NO concentration will be halved.

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥18 years
  2. Diagnosed Covid-19 infection
  3. Severe cases of Covid-19 infection needs mechanical ventilation

Exclusion Criteria:

  1. Physician makes a decision that trial involvement is not in the patient's best interest or any condition that does not allow the protocol to be followed safely
  2. Pregnant or positive pregnancy test in a pre-dose examination
  3. mechanical ventilation initiated for more than 48 hrs
  4. Rescue Use ECMO
  5. With severe organ dysfunction or failure (Child Pugh≥12, eGFRC30 ml/min/1.73m2, on RRT or dialysis)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment Group
Nitric Oxide gas will be administered in the ventilatory circuit.
Drug: Nitric Oxide Gas
Inspired NO/N2 will be delivered at 80 parts per million (ppm) in the first 48 hours of enrollment (within 48 hours after initiation of mechanical ventilation). Weaning from NO will start after 48-h consecutive NO inhalation. The physicians will follow their own institutional weaning protocols.
Other Names:
  • Nitric Oxide inhalation
SHAM_COMPARATOR: Control Group
The delivery system will be set up anyway without study gas administration
Other: The delivery system will be set up anyway without study gas administration
The delivery system will be set up anyway without study gas administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ventilation free days (VFDs)
Time Frame: 28 days since beginning of treatment
count the days that patients do not need mechanical ventilation
28 days since beginning of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival at 28 days
Time Frame: 28 days
count the number of patients that survive to 28 days after randomization
28 days
Survival at 90 days
Time Frame: 90 days
count the number of patients that survive to 90 days after randomization
90 days
WHO COVID Ordinal Outcomes Scale
Time Frame: 28 days
8 score scale, where no limitation of activity =1, death = 8
28 days
time to improvement of oxygenation
Time Frame: through oxygenation improvement, an average of 2 days
time from randomization to PaO2/FiO2 ≥300 at room air
through oxygenation improvement, an average of 2 days
MODS needs life support
Time Frame: 28 days
Incidence of organ failure need support of RRT, VA-ECMO, LVAD, IABP, Prone ventilation, etc
28 days
duration of mechanical ventilation
Time Frame: through wean of mechanical ventilation, an average of 10 days
days when mechanical ventilation are used
through wean of mechanical ventilation, an average of 10 days
Length of ICU stay and hospital stay
Time Frame: through discharge from ICU or hospital, an average of 20 days
count days when patients stay in ICU and hospital
through discharge from ICU or hospital, an average of 20 days
SOFA score
Time Frame: at 48 hours, 72 hours, and 7 days after randomization
Sequential (sepsis-related) organ failure assessment (SOFA) score.
at 48 hours, 72 hours, and 7 days after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xijing Hospital

Collaborators

Massachusetts General Hospital
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

January 16, 2023

Primary Completion (ANTICIPATED)

December 31, 2023

Study Completion (ANTICIPATED)

April 1, 2024

Study Registration Dates

First Submitted

February 27, 2020

First Submitted That Met QC Criteria

February 27, 2020

First Posted (ACTUAL)

March 2, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2023

Last Update Submitted That Met QC Criteria

February 5, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NO-SARS-COVID-19

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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