Efficacy and Safety of IV Sildenafil in the Treatment of Newborn Infants With, or at Risk of Persistent Pulmonary Hypertension of the Newborn (PPHN): A Multicenter, Randomized, Placebo-Controlled Trial
Abstract
OBJECTIVE
To investigate the efficacy and safety 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.
STUDY DESIGN
Part A of a multinational, randomized, double-blind, placebo-controlled trial. Infants ≤96hrs-old, >34 weeks of gestation, receiving iNO (10-20ppm on ≥50% FiO2) for PPHN or HRF at risk of PPHN, and oxygen index >15-<60, were randomized (1:1) to IV sildenafil (loading: 0.1mg/kg, over 30 mins; maintenance: 0.03mg/kg/h) or placebo, for up to 14 days. Coprimary endpoints were treatment failure rate (day 14/discharge) and time on iNO without treatment failure. Secondary endpoints included time on ventilation and oxygenation measures.
RESULTS
Of 87 infants screened, 29 were randomized 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). Treatment failure rates did not differ with sildenafil (27.6%) vs. placebo (20.0%; P=0.4935). Mean time on iNO was not different with sildenafil (4.1-days) vs placebo (4.1-days; P=0.9850). No differences were noted in secondary endpoints. Most common adverse events (AEs) with sildenafil (≥10% infants) were: hypotension (n=8/29), hypokalemia (n=7/29), anemia, drug withdrawal syndrome (n=4/29, each), bradycardia (n=3/29). One serious AE (hypotension) was considered treatment-related.
CONCLUSION
IV sildenafil added to…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 87 participants or records.
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