Clinical trial NCT04338828: Nitric Oxide Inhalation Therapy for COVID-19 Infections in the ED
Official title: Nitric Oxide Inhalation Therapy for COVID-19 Infections in the Emergency Department
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID19
Keywords: inhaled nitric oxide
emergency department
emergency medicine
respiratory infection
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2020-04-08
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rates of return visits to the ED
timeFrame: 28 days
Secondary outcomes:
measure: Inpatient hospitalizations required
timeFrame: 28 days
measure: Rates of intubation
timeFrame: 28 days
measure: Rates of mortality
timeFrame: 28 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References: