A clinical trial to evaluate the effects of inhaled nitric oxide gas among COVID-19 patients with pneumonia

INTERVENTION: Eligible patients will be randomized into two arms either receiving standard of care only (control arm), or standard of care and inhaled Nitric Oxide (iNO) using a helmet or tight sealing oronasal mask (case arm). iNO will be deluvered as pulses lasting for 30 min at 12 h intervals, for 3 consecutive days. iNO will be administered at the minimum FiO2 to maintain saturations above 92%, using a V60 bilevel positive airway pressure (BiPAP) machine. The flow rates will be titrated to administer escalating doses of iNO starting from 10 ppm to 80 ppm over a period of 30 min. Following this iNO will be weaned off at the rate of 10 ppm per min. Study patients will be started on oral Sildenafil 10 mg TID for 5 days, to prevent rebound rise in pulmonary pressures after iNO discontinuation, provided their MAP is >60 mmHg. Standard of care therapies including antivirals, steroids, anticoagulants, and other medications will be administered in both study arms as per institutional protocol. CONDITION: Adult COVID‐19 pneumonia patients with hypoxic respiratory failure ; Infections and Infestations ; COVID‐19 (SARS‐CoV‐2 infection) PRIMARY OUTCOME: Viral load as defined by cycle threshold measured using Real‐Time Polymerase Chain Reaction Surrogate CT ratio from nasopharyngeal swab collected at baseline 3, 5, 7, 10, and 14 days SECONDARY OUTCOME: ; 1. Duration of non‐invasive ventilation (NIV) measured from the nursing chart and medical record evaluation recorded at 8 am and 8 pm daily by investigators during the study period collected at end of NIV; 2. Duration of oxygen therapy measured from the nursing chart and medical record evaluation recorded at 8 am and 8 pm daily by investigators during the study period collected at end of oxygen therapy; 3. Methaemoglobin levels measured using arterial blood gas analysis using a co‐ oximeter RADIOMETER ABL 800 on blood gas samples drawn after each pulse of iNO therapy at baseline, 1, 2, and 3 days; 4. Incidence of methaemoglobin levels >3% during the trial measured using arterial blood gas analysis using a co‐ oximeter RADIOMETER ABL 800 on blood gas samples drawn after each pulse of iNO therapy at baseline, 1, 2, and 3 days; 5. Severe acute respiratory infection (SARI) scale performance assessed during daily rounds by the clinical team collected daily until ICU discharge or achievement of the lowest numeric, whichever is earlier; 6. Patient status measured using the Sequential Organ Failure Assessment (SOFA) score from medical chart/investigations obtained at 8 am at baseline and 72 h; 7. Length of hospital stay measured from medical chart review on the day of hospital discharge; 8. Length of intensive care unit (ICU) stay measured from medical chart review on the day of ICU discharge; 9. Deaths measured by investigators for all patients in each arm and followed up daily recorded on the day of death or the immediate day after; INCLUSION CRITERIA: 1. Severe acute respiratory infection (SARI) class 4 and 5 (hospitalized with the requirement of oxygen supplementation, high flow oxygen device, or non‐invasive ventilation assistance) 2. Respiratory rates <30 and saturating >90% with oxygen or Non‐Invasive Ventilation (NIV)