Nitric Oxide Inhalation Therapy for COVID-19 Infections in the ED (NO COV-ED)

Nitric Oxide Inhalation Therapy for COVID-19 Infections in the Emergency Department

The spread of novel Coronavirus (2019-nCoV) related infection (COVID-19) has led to many patient presentations in the emergency department for respiratory complaints, with many of these patients requiring ICU admission and ventilatory support. While COVID-19 patients have an increased need for supportive care, there is currently no specific treatment directed against 2019-nCoV. Nitric oxide inhalation has been used as a pulmonary vasodilator and has been found to have antiviral activity against other coronavirus strains. The primary aim of this study is to determine whether inhaled NO improves short term respiratory status, prevents future hospitalization, and improves the clinical course in patients diagnosed with COVID-19 specifically in the emergency department.

Study Overview

• Status: Terminated
• Conditions: COVID19
• Intervention / Treatment: Drug: Nitric Oxide Gas; Other: Inhaled Supplemental Oxygen

Detailed Description

The spread of novel Coronavirus (2019-nCoV) related infection (COVID-19) has led to many patient presentations in the emergency department for respiratory complaints, with many of these patients requiring ICU admission and ventilatory support. While COVID-19 patients have an increased need for supportive care, there is currently no specific treatment directed against 2019-nCoV. Nitric oxide inhalation has been used as a pulmonary vasodilator and has been found to have antiviral activity against other coronavirus strains.

Preliminary data support a microbicidal effect of high concentration inhaled NO. We hypothesize that high concentration inhaled NO can have a viricidal effect against SARS-Cov-2 and prevent the deterioration to a severe form of COVID-19 when administered at an early stage of the disease. Additional potential mechanisms why INO may be effective in this indication: 1)improves V/Q ratio, 2) reduces PVR and PAP, 3) Anti-thrombotic in lung. This would have potential benefit for the patients in terms of reducing the severity of the clinical course and time to recovery. An additional benefit could be for the society since a faster and a less severe clinical course could protect limited hospital resources (ED, floor, and ICU) from being overwhelmed.

The primary aim is to prevent the deterioration of mild COVID-19 infection (defined by a RT-PCR positive for SARS-CoV-2 in a specimen from any site) with respiratory signs/ symptoms to a more severe form of the disease as defined by the patient needing to 1) return to the ED, 2) be admitting to the hospital, 3) be intubated, 4) and all cause 28 day mortality.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years old
• Presentation to the ED with respiratory symptoms likely caused by COVID-19

• Patient displays at least one of the following

  1. respiratory rate ≥ 24
  2. new cough
  3. new atypical chest pain
  4. new dyspnea
  5. oxygen saturation < 97% at rest
  6. chest x-ray with new changes consistent with COVID-related airspace disease
• Cleared for discharge home by attending physician
• Obtained COVID testing (results not required at time of enrollment)
• Onset of symptoms ≤12 days prior to ED visit

Exclusion Criteria:

• Attending physician estimation (< 50% likelihood) of other more likely non-COVID etiology
• Presence of tracheostomy
• Requirement of oxygen therapy to maintain resting oxygen saturation of > 94%
• Clinical contraindication to use of inhaled nitric oxide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Inhaled nitric oxide	Drug: Nitric Oxide Gas; Inhaled NO administered at target inspired concentration 140 - 300 ppm for 20-30 minutes
Placebo Comparator: Control Group; Inhaled supplemental oxygen	Other: Inhaled Supplemental Oxygen; 2 L/min oxygen therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of return visits to the ED	Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to return to the ED with worsening symptoms	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inpatient hospitalizations required	Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to require hospitalization during their COVID-19 course	28 days
Rates of intubation	Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to require intubation during their COVID-19 course	28 days
Rates of mortality	Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to die of any cause within 28 days of their initial ED visit	28 days

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2020
• Primary Completion (Actual): January 14, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: April 5, 2020
• First Submitted That Met QC Criteria: April 5, 2020
• First Posted (Actual): April 8, 2020

Study Record Updates

• Last Update Posted (Actual): January 6, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: emergency department; respiratory infection; emergency medicine; inhaled nitric oxide
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: 2019P00XXXX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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