The primary objective of this study is to provide expanded access of S-nitrosylation therapy for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection.
Randomized controlled trial for safety of a 6-hour escalating dose of S-nitrosylation therapy or placebo to ventilated patients. This will be a single-site study conducted within the UH-CMC medical ICU designated COVID-19 quarantine areas.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Six-hour SNO treatment by inhalation at a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr. Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization.
Six-hour nitrogen gas treatment by inhalation.Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization.
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Treatment Emergent Adverse Events
Adverse events related to SNO therapy.
Time frame: 30 days
Frequency of Intubation
Number of intubations required.
Time frame: 30 days
Progression to use of ECMO
Use of ECMO required.
Time frame: 30 days
Time to Clinical Status Improvement
Number of days required to see a greater than or equal to 2 point improvement on the WHO 9-point clinical status assessment ordinal scale. Clinical status will be assessed using the WHO 9-point ordinal scale as follows: 0\. Uninfected - no clinical or virological evidence of infection 1. Ambulatory - no limitation of activities 2. Ambulatory - Limitation of activities 3. Hospitalized, mild disease - no oxygen therapy 4. Hospitalized, mild disease - oxygen by mask or nasal prongs 5. Hospitalized, severe disease - non-invasive ventilation or high-flow oxygen 6. Hospitalized, severe disease - intubation and mechanical ventilation 7. Hospitalized, severe disease - ventilation + additional organ support (pressors, RRT, ECMO) 8. Dead
Time frame: 30 days
Clinical Status
Proportion of patients in each stage at maximum severity on the 9-point clinical status assessment ordinal scale. Clinical status will be assessed using the WHO 9-point ordinal scale as follows: 0\. Uninfected - no clinical or virological evidence of infection 1. Ambulatory - no limitation of activities 2. Ambulatory - Limitation of activities 3. Hospitalized, mild disease - no oxygen therapy 4. Hospitalized, mild disease - oxygen by mask or nasal prongs 5. Hospitalized, severe disease - non-invasive ventilation or high-flow oxygen 6. Hospitalized, severe disease - intubation and mechanical ventilation 7. Hospitalized, severe disease - ventilation + additional organ support (pressors, RRT, ECMO) 8. Dead
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Time frame: 30 days
Respiratory Clinical Status
Respiratory clinical status assessed by a 7-point respiratory status ordinal scale that captures oxygen requirement, ventilator support or death. 7-Point Respiratory Severity Scale Range: 1-7 Higher values = worse 1. Not receiving oxygen supplementation; AND room air oxygen saturation ≥ 95% 2. Supplemental oxygen ≤ 2 liters/min; OR room air oxygen saturation ≤ 94% 3. Supplemental nasal oxygen \>2 and \<= 5 liters/min 4. Supplemental nasal oxygen \>5 liters/min 5. HFNC or NIV with FiO2 \> 50% 6. Intubation or ECMO 7. Death
Time frame: 30 days
Duration of Hospitalization
Duration of total hospitalization days as measured by total hospitalization, ventilator and ICU days
Time frame: 30 days
All-Cause Mortality
All-cause mortality
Time frame: 30, 60 days
Time to Discontinuation of Oxygen Therapy
Number of days required to discontinue oxygen supportive therapy
Time frame: 30 days
Discontinuation of Oxygen Therapy
Proportion of patients alive and with discontinued oxygen supportive therapy at day 30
Time frame: 30 days