Randomized Controlled Trials of Pulmonary Vasodilator Therapy Adjunctive to Inhaled Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn: A Systematic Review

This systematic review demonstrates that recruitment challenges limit the ability to draw conclusions regarding the efficacy and safety of pulmonary vasodilator therapy adjunctive to iNO for PPHN. The results demonstrate several complexities inherent to recruiting critically ill neonates with an increasingly rare disease. Overcoming these barriers is ethically necessary. The authors suggest that a PPHN consortium may address issues of heterogeneity in eligibility criteria and outcomes and propose that alternative trial design strategies are necessary. These may include deferred consent, real -world controls, nonrandomized database assessments, and Bayesian statistical approaches.