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0 0.5 1 1.5 2+ Mortality 90% Improvement Relative Risk Ventilation 90% <2 point WOS improvem.. 42% Time to viral load reduc.. 64% Time to viral load r.. (b) 63% Nitric Oxide  Moni et al.  ICU PATIENTS  RCT Is very late treatment with nitric oxide beneficial for COVID-19? RCT 25 patients in India (September - December 2020) Lower mortality (p=0.026) and ventilation (p=0.026) Moni et al., Infectious Microbes and D.., Apr 2021 Favors nitric oxide Favors control

Clinical Efficacy of Inhaled Nitric Oxide in Preventing the Progression of Moderate to Severe COVID-19 and Its Correlation to Viral Clearance: Results of a Pilot Study

Moni et al., Infectious Microbes and Diseases, doi:10.1097/IM9.0000000000000079 (date from preprint), ISRCTN16806663
Apr 2021  
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RCT 29 ICU patients in India, showing improved clinical outcomes and faster viral clearance with inhaled nitric oxide treatment. The treatment group was younger (mean 54 vs. 66) and had more patients on NIV at baseline (29% vs. 18%).
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects (early treatment may be more beneficial).
risk of death, 90.1% lower, RR 0.10, p = 0.03, treatment 0 of 14 (0.0%), control 4 of 11 (36.4%), NNT 2.8, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 28.
risk of mechanical ventilation, 90.1% lower, RR 0.10, p = 0.03, treatment 0 of 14 (0.0%), control 4 of 11 (36.4%), NNT 2.8, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 28.
risk of <2 point WOS improvement, 42.5% better, RR 0.58, p = 0.47, treatment 3 of 14 (21.4%), control 7 of 11 (63.6%), NNT 2.4, adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk, day 14.
time to viral load reduction, 64.4% lower, RR 0.36, p = 0.005, treatment 14, control 11, adjusted per study, inverted to make RR<1 favor treatment, N gene.
time to viral load reduction, 63.4% lower, RR 0.37, p = 0.005, treatment 14, control 11, adjusted per study, inverted to make RR<1 favor treatment, Orf1ab gene.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Moni et al., 20 Apr 2021, Randomized Controlled Trial, India, peer-reviewed, 16 authors, study period September 2020 - December 2020, average treatment delay 6.78 days, trial ISRCTN16806663.
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Clinical Efficacy of Inhaled Nitric Oxide in Preventing the Progression of Moderate to Severe COVID-19 and Its Correlation to Viral Clearance: Results of a Pilot Study
Merlin Moni, Thushara Madathil, Dipu T Sathyapalan, Veena Menon, Georg Gutjahr, Fabia Edathadathil, Deepthi Sureshkumar, Preetha Prasanna, Soumya Jose, Roshni Jerome, Ajai Krishnan, Indulekha C L Pillai, Geetha Kumar, Bipin Nair, Victor Nizet, Aveek Jayant
Infectious Microbes and Diseases, doi:10.1097/im9.0000000000000079
Hypoxic patients with coronavirus disease 2019 (COVID-19) are at high risk of adverse outcomes. Inhaled nitric oxide (iNO) has shown anti-viral and immunomodulatory effects in vitro. However, in vivo evidence of efficacy in hypoxic COVID-19 is sparse. This open label feasibility study was conducted at a single referral center in South India and evaluated the effectiveness of repurposed iNO in improving clinical outcomes in COVID-19 and its correlation with viral clearance. We recruited hypoxemic COVID-19 patients and allocated them into treatment (iNO) and control groups (1:1). Viral clearance on day 5 favored the treatment group (100% vs 72%, P < 0.01). The speed of viral clearance as adjudged by normalized longitudinal cycle threshold (Ct) values was positively impacted in the treatment group. The proportion of patients who attained clinical improvement, defined as a ≥2-point change on the World Health Organization ordinal scale, was higher in the iNO cohort (n = 11, 79%) as compared to the control group (n = 4, 36%) (odds ratio 6.42, 95% confidence interval 1.09-37.73, P = 0.032). The proportion of patients progressing to mechanical ventilation in the control group (4/11) was significantly higher than in the treatment group (0/14). The all-cause 28-day mortality was significantly different among the study arms, with 36% (4/11) of the patients dying in the control group while none died in the treatment group. The numbers needed to treat to prevent an additional poor outcome of death was estimated to be 2.8. Our study demonstrates the putative role of repurposed iNO in hypoxemic COVID-19 patients and calls for extended validation.
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Late treatment
is less effective
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