Inhaled nitric oxide for the treatment of COVID-19: an open-label, parallel, randomised controlled trial

Background: Inhaled nitric oxide (iNO) in high concentration inhibits SARS-CoV-2 replication in epithelial cells and may prevent severe disease in hospitalised patients. The aim of this study was to evaluate safety and efficacy of iNO 160 ppm on supplemental oxygen in patients hospitalised with COVID-19. Methods: We conducted an open-label, randomised clinical trial in hospitalised patients with COVID-19 receiving supplemental oxygen. Patients were randomly assigned to receive iNO for 6 h in addition to standard of care. The primary safety end-point was assessed by incidence of adverse events. The secondary efficacy end-point was the number of days free of supplemental oxygen within 15 days after randomisation. Results: 55 patients were enrolled, 27 in the iNO group and 27 in the control group, and one patient was excluded. No adverse events occurred with the inhalation of nitric oxide. Median (IQR) number of days free of supplemental oxygen was 11 (8.0-13.0) in the iNO group and 8 (2.5-10.5) in the control group (p=0.044). The iNO group had a shorter length of hospital stay (4.5 days (3.0-6.3) compared to 7.0 days (6.0-10.0) in the control group; p=0.004). Clinical score was lower in the iNO group on days 3 and 5 (p=0.010 and p=0.033). The number of patients weaned from ventilatory support on day 3 was higher in the iNO group (n=9 (33%)) when compared to controls (n=1 (4%)); p=0.005. Respiratory failure and mortality did not differ between the groups. Conclusion: The iNO treatment was well tolerated and safe. Among adults hospitalised for COVID-19, iNO 160 ppm for 6 h increased the number of days free from supplemental oxygen, shortened the days of ventilatory support and the length of hospital stay, and improved the clinical score.