Background: An international multicenter, placebo-controlled, double-blind study (STARTS-1) and its subsequent extension study (STARTS-2) demonstrated that sildenafil monotherapy with medium dose was well tolerated and improved exercise tolerance, functional class, and hemodynamics in patients with pediatric pulmonary arterial hypertension (PAH). However, clinical studies of pediatric PAH had not been performed in Japan at the time. We therefore aimed to investigate the efficacy, safety and pharmacokinetics of sildenafil in Japanese pediatric patients with PAH.

Methods: We conducted an open-label study consisting of both a 16-week treatment period (Part 1) and a long-term treatment period (Part 2). The efficacy endpoints were improvement in the parameters of pulmonary vascular resistance index (PVRI), mean pulmonary arterial pressure (mPAP), World Health Organization functional class, brain natriuretic peptide (BNP) and N-terminal pro-BNP. The patients received sildenafil at 10 mg or 20 mg that was administered 3 times a day based on body weight.

Results: Six children aged 1 to 14 years with PAH were screened, and sildenafil was assigned. Four patients completed Part 1, and one patient completed Part 2. In Part 1, among the 5 patients with available cardiac catheterization data, PVRI and mPAP decreased in 3 and 2 patients, respectively. There were 11 treatment-related adverse events that were already known, but no serious adverse events including death occurred.

Conclusions: This study suggests that oral sildenafil is well tolerated and acceptable as a therapeutic option in Japanese pediatric patients with PAH. (Clinical Trial Registration: NCT01642407)