Randomized controlled trials of pulmonary vasodilator therapy adjunctive to inhaled nitric oxide for persistent pulmonary hypertension of the newborn: A systematic review

Inhaled nitric oxide (iNO) is a pulmonary vasodilator considered standard of care to treat persistent pulmonary hypertension of the newborn. However, not all infants respond to iNO. We performed a systematic review to examine methodology, outcomes and challenges of randomized controlled trials testing pulmonary vasodilator medications adjunctive to iNO. The five trials identified showed heterogeneity in eligibility criteria and outcomes assessed. No trial achieved recruitment goals, limiting conclusions regarding efficacy, safety and pharmacology, despite overall high methodologic quality. Trial design consensus and alternative methodologic strategies such as deferred consent, real-world controls, non-randomized database assessments, and Bayesian statistical approaches are needed.