A Feasibility Trial to Evaluate the Composite Efficacy of Inhaled Nitric Oxide in the Treatment of Covid 19 Pneumonia : Impact on Viral Load and Clinical Outcomes

Moni, M.; Madathil, T.; Sathyapalan, D.; Menon, V.; Gutjahr, G.; Edathadathil, F.; Sureshkumar, D.; Prasanna, P.; Jose, S.; Jerome, R.; Krishnan, A.; Pillai, I.; Kumar, G.; Nair, B.; Jayant, A.

Background: Hypoxic patients with Covid 19 pneumonia are at high risk of adverse outcomes. Inhaled Nitric Oxide (iNO) inhibits viral entry and replication of SARS-CoV2 and in vivo proof of its antiviral actions is unavailable to date. This feasibility study was conducted to test the antiviral effects of iNO and to describe clinical outcomes. Methods: The phase II open label, randomised controlled feasibility trial(ISRCTN 16806663) conducted at a South Indian tertiary care referral centre, recruited COVID-19 pneumonia patients with hypoxic respiratory failure and allocated them into iNO cases and control groups(1:1). iNO was administered as pulses for 30 minutes for three consecutive days at 12-hour intervals in cases, in addition to standard of care received by the control group. The primary outcome was decline in viral load, as defined by a surrogate change in the RT-PCR cycle threshold. The co-primary clinical outcome was time to improvement of >2 points on the WHO Ordinal Scale(WOS). Results: Among the 29 patients enrolled, 14 iNO cases and 11 controls completed the study protocol. Longitudinal analysis revealed a significant difference in the decline (p <0.002, N= 23) in viral load among the iNO cases compared to controls. The proportion of patients achieving 2-point improvement in the WOS within 14 days of randomisation was significantly higher in the iNO cases (n=11, 79%), as compared to the controls (n=4, 36%) (p=0.05). Conclusions: Our study demonstrated significant improvement in virological and clinical outcomes among patients with adjunct iNO therapy and no adverse effects were reported.