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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04338828
• Collaborator: (none)
• Enrollment: 47
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.4
• Patients Per Site Per Month: 4.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
COVID19	Drug: Nitric Oxide Gas; Other: Inhaled Supplemental Oxygen	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Nitric Oxide Inhalation Therapy for COVID-19 Infections in the Emergency Department
• Actual Study Start Date: Apr 18, 2020
• Actual Primary Completion Date: Jan 14, 2021
• Actual Study Completion Date: Mar 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Rates of return visits to the ED [28 days]

   Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to return to the ED with worsening symptoms

Secondary Outcome Measures

1. Inpatient hospitalizations required [28 days]

   Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to require hospitalization during their COVID-19 course

2. Rates of intubation [28 days]

   Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to require intubation during their COVID-19 course

3. Rates of mortality [28 days]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: N. Stuart Harris MD MFA, Principal Investigator, Division Chief of Wilderness Medicine, Department of Emergency Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT04338828
• Other Study ID Numbers: 2019P00XXXX
• First Posted: Apr 8, 2020
• Last Update Posted: Jan 6, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by N. Stuart Harris MD MFA, Principal Investigator, Division Chief of Wilderness Medicine, Department of Emergency Medicine, Massachusetts General Hospital: inhaled nitric oxide; emergency department; emergency medicine; respiratory infection
• Additional relevant MeSH terms: Infections; COVID-19; Nitric Oxide

Study Results

No Results Posted as of Jan 6, 2022