High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure due to COVID-19: A Multicenter Phase 2 Trial.
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Di Fenza R, Shetty NS, Gianni S, Parcha V, Giammatteo V, Safaee Fakhr B, Tornberg D, Wall O, Harbut P, Lai PS, Li JZ, Paganoni S, Cenci S, Mueller AL, Houle TT, Akeju O, Bittner EA, Bose S, Scott LK, Carroll RW, Ichinose F, Hedenstierna M, Arora P, Berra L
Am J Respir Crit Care Med - (-) - [2023-09-29; online 2023-09-29]
The effects of high-dose inhaled nitric oxide on hypoxemia in COVID-19 acute respiratory failure are unknown. Mechanically ventilated adults with COVID-19 pneumonia were enrolled in a phase II, multicenter, single-blind, randomized, controlled, parallel-arm trial. Participants in the intervention arm received inhaled nitric oxide at 80 parts-per-million (ppm) for 48h, compared with the control group receiving usual care (without placebo). The primary outcome was the change in arterial oxy-genation (PaO2/FiO2) at 48h. The secondary outcomes included: time to reach a PaO2/FiO2>300 mmHg for at least 24h, the proportion of participants with a PaO2/FiO2>300 mmHg at 28 days, and survival at 28- and 90-days. 193 participants were included in the modified intention-to-treat analysis. The mean change in PaO2/FiO2 ratio at 48h was 28.3 mmHg in the intervention group and -1.4 mmHg in the control group (mean difference: 39.1 mmHg (95%CrI:18.1-60.3). The mean time to reach a PaO2/FiO2>300 mmHg in the interventional group was 8.7 days com-pared to 8.4 days for the control group (mean difference:0.44(95%CrI:-3.63 to 4.53)). At 28 days, the proportion of participants attaining a PaO2/FiO2>300 mmHg was 27.7% in the inhaled nitric oxide group and 17.2% in the controls (RR:2.03(95%CrI:1.11 to 3.86)). Duration of ventilation and mortality at 28 and 90 days did not differ. No serious adverse events were reported. The use of high-dose inhaled nitric oxide resulted in an improvement of PaO2/FiO2 at 48h compared with usual care in adults with acute hypoxemic respiratory failure due to COVID-19. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www. gov, ID: NCT04306393.
PubMed 37774011
DOI 10.1164/rccm.202304-0637OC
Crossref 10.1164/rccm.202304-0637OC