Pierce CM, Zhang MH, Jonsson B, et al. - In this multicenter, randomized, placebo-controlled trial, researchers tested the safety and effectiveness of sildenafil added to inhaled nitric oxide (iNO) for newborn infants with persistent pulmonary hypertension of newborn (PPHN) or hypoxic respiratory failure (HRF) at risk of PPHN. For up to 14 days, infants ≤ 96hrs-old, > 34 weeks of gestation, receiving iNO (10-20 ppm on ≥ 50% FiO2) for PPHN or HRF at risk of PPHN, and oxygen index > 15-< 60, were randomized (1:1) to IV sildenafil (loading: 0.1 mg/kg, over 30 mins; maintenance: 0.03 mg/kg/h) or placebo. Of the 87 infants screened, 29 were randomly assigned to IV sildenafil and 30 to placebo; 13 discontinued treatment (sildenafil, n = 6; placebo: n = 7), including 3 deaths (sildenafil: n = 2; placebo: n = 1). The most common adverse events were hypotension, hypokalemia, anemia, drug withdrawal syndrome, bradycardia. In infants with PPHN or HRF at risk of PPHN, IV sildenafil combined with iNO was not superior to placebo. A review of adverse events revealed no pattern of events suggestive of a safety issue with IV sildenafil.