Inhaled Nitric Oxide for the Treatment of Acute Bronchiolitis: A Multicenter Randomized Controlled Clinical Trial to Evaluate Dose Response

Autor: Aviv Goldbart, Moran Lavie, Ronit Lubetzky, Giora Pillar, Daniel Landau, Yechiel Schlesinger, Ronen Spiegel, Inbal Golan-Tripto, Amit Nahum, David Greenberg, Asher Tal
Rok vydání: 2023
Předmět:
Zdroj: Annals of the American Thoracic Society. 20:236-244
ISSN: 2325-6621
2329-6933
DOI: 10.1513/annalsats.202103-348oc
Popis: Inhaled nitric oxide (iNO) has potential anti-inflammatory, anti-microbial, and anti-viral properties for patients with lower respiratory tract infections.We compared the safety and efficacy of iNO administered in two concentrations in addition to standard supportive treatment (SST) compared to SST alone with the aim to improve clinical outcomes of infants with bronchiolitis.In this prospective, multicenter, double-blind, randomized-controlled study, 89 infants hospitalized with moderate-severe bronchiolitis were randomly assigned to three treatment groups: 150 parts per million (ppm) NO+SST(1); 85 ppm NO+SST(2); and the control treatment O2/air+SST(3). Treatment was given for 40 minutes, 4 times/day for up to 5 days. The primary endpoint was time to reach "fit for discharge". This was a composite endpoint comprised of both reaching a sustained oxygen saturation (SpO2) ≥92% in room air, and reaching a clinical score ≤5. Secondary endpoints included time to reach sustained SpO2 ≥92% in room air, time to clinical score ≤5, and time to hospital discharge. Safety was assessed by the number of treatment-related adverse-events (AEs) or serious adverse-events (SAEs). Time-to-event efficacy outcomes were analyzed by Cox proportional-hazards regression-model. Hazard ratio (HR) describes how many times more likely an individual is to experience an event, if such an individual receives the NO rather than the control treatment during the observational period.Group 1 demonstrated significant efficacy for time to reach "fit to discharge" compared to Groups 2 (HR=2.11, p=0.041) and 3 (HR=2.32, p=0.049). Group 1 also demonstrated significant efficacy for time to hospital discharge compared to Groups 2 (HR=2.01, p=0.046) and 3 (HR=2.28, p=0.043). No significant differences were observed between Groups 2 and 3 for either endpoint. There were no differences between treatment groups in time to reach clinical score ≤5. The iNO therapy was well-tolerated with no treatment-related SAEs.Treatment with high dose intermittent iNO at 150 ppm showed reduced time to clinical improvement when compared to 85 ppm or control treatment of hospitalized infants with acute bronchiolitis. The 150 ppm iNO dose is well-tolerated, with significant benefit compared to both standard therapy and 85 ppm iNO, improving respiratory outcome and reducing length of stay.
Databáze: OpenAIRE
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