A phase-III multicenter, randomized, double-blind, controlled trial of high-dose inhaled nitric oxide in infants with acute bronchiolitis.

Abstract

Acute viral bronchiolitis is the most common lower respiratory infection in early infancy and a leading cause of infant hospitalization. The treatment of bronchiolitis is largely supportive. Inhaled nitric oxide (NO) has pulmonary vasodilatory properties and has been approved for the treatment of persistent pulmonary hypertension of the newborn. Furthermore, preclinical studies show that high-dose NO possesses anti-bacterial and anti-viral properties. In a recent pilot study, we have shown safety and tolerability of high-dose NO (160 ppm) in infants with moderately severe bronchiolitis. In this study, we are conducting a randomized, multicenter, double-blind, controlled pivotal trial comparing the efficacy of intermittent 160 ppm NO (30min, 5 times/day, up to 5 days) with standard supportive care (O2/air) in 94 infants (0-12 months old, clinical score 7-10, requiring >24hr hospitalization) admitted to 10 hospitals across Israel. All subjects receive standard of care treatment. The primary outcome measure is the length of hospital stay (LOS). The secondary outcome measures are time to reach clinical score of 5 and below (Modified Tal score) and time to reach O2 saturation of 92% and above in room air. Adverse events (AE’s) and NO-related AE’s including methemoglobin and nitrogen dioxide levels are closely monitored. At the time of submission, the trial is ongoing with 46 out of 94 subjects enrolled at 5 sites. We anticipate demonstrating efficacy by reducing LOS and improving clinical symptoms in infants treated with NO. We predict completing the trial by April 30, 2018 and present final results at the next 2018 ERS International meeting, Paris.