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 hospitalized patients. To evaluate safety and efficacy of inhaled nitric oxide 160 ppm on supplemental oxygen in patients hospitalized with COVID-19. Methods We conducted an open-label, randomized clinical trial in hospitalized 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 endpoint was assessed by incidence of adverse events (AEs). The secondary efficacy endpoint was the number of days free of supplemental oxygen within 15 days after randomization. Results Fifty-five 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 NO. Number of days free of supplemental oxygen (median, IQR) was 11 (8.0 to 13.0) in the iNO group and 8 (2.5 to 10.5) in the control group; p=0.044. The iNO group had a shorter length of hospital stay, 4.5 days (3.0 to 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 hospitalized for COVID-19, iNO 160 ppm for 6 h increased the number of days free from supplemental oxygen, shortened the days of ventilatory support, the length of hospital stay and improved the clinical score. Clinical trial registration: ensaiosclinicos.gov.br, Identifier: RBR-8nfx26