Nitric Oxide Inhalation Therapy for COVID-19 Infections in the ED (NO COV-ED)
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ClinicalTrials.gov Identifier: NCT04338828 |
Recruitment Status :
Terminated
(Absence of patients meeting criteria following initial COVID surge. DMSB recommended analysis of results to date and early closure.)
First Posted : April 8, 2020
Last Update Posted : January 6, 2022
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Condition or disease | Intervention/treatment | Phase |
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COVID19 | Drug: Nitric Oxide Gas Other: Inhaled Supplemental Oxygen | Phase 2 |
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 (Clinical Trial) |
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 : | April 18, 2020 |
Actual Primary Completion Date : | January 14, 2021 |
Actual Study Completion Date : | March 1, 2021 |

Arm | Intervention/treatment |
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Experimental: Treatment Group
Inhaled nitric oxide
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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
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Other: Inhaled Supplemental Oxygen
2 L/min oxygen therapy |
- Rates of return visits to the ED [ Time Frame: 28 days ]Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to return to the ED with worsening symptoms
- Inpatient hospitalizations required [ Time Frame: 28 days ]Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to require hospitalization during their COVID-19 course
- Rates of intubation [ Time Frame: 28 days ]Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to require intubation during their COVID-19 course
- Rates of mortality [ Time Frame: 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

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
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
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Patient displays at least one of the following
- respiratory rate ≥ 24
- new cough
- new atypical chest pain
- new dyspnea
- oxygen saturation < 97% at rest
- 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

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): NCT04338828
United States, Massachusetts | |
Massachusetts General Hospital | |
Boston, Massachusetts, United States, 02114 |
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: | April 8, 2020 Key Record Dates |
Last Update Posted: | January 6, 2022 |
Last Verified: | December 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
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 |
inhaled nitric oxide emergency department emergency medicine respiratory infection |
Infections COVID-19 Respiratory Tract Infections Pneumonia, Viral Pneumonia Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases Respiratory Tract Diseases 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 Gasotransmitters Protective Agents |