Journal of Pediatric Cardiology and Cardiac Surgery

Online ISSN: 2433-1783 Print ISSN: 2433-2720
Japanese Society of Pediatric Cardiology and Cardiac Surgery
Japanese Society of Pediatric Cardiology and Cardiac Surgery Academy Center, 358-5 Yamabuki-cho, Shinju-ku, Tokyo 162-0801, Japan
Journal of Pediatric Cardiology and Cardiac Surgery 3(2): 88-96 (2019)

Original ArticleOriginal Article

Efficacy and Safety of Sildenafil in Japanese Pediatric Patients with Pulmonary Arterial Hypertension

1Department of Pediatrics and Neonatology, Osaka General Medical Center ◇ Osaka, Japan

2Department of Pediatrics, Osaka University Graduate School of Medicine ◇ Osaka, Japan

3Advanced and Integrated Cardiovascular Research Course in the Young and Adolescence, Toho University ◇ Tokyo, Japan

4Division of Cardiology, National Center for Child Health and Development ◇ Tokyo, Japan

5Ishii Pediatrics and Pediatric Cardiology Office ◇ Kanagawa, Japan

6Department of Pediatrics, Kitasato University Hospital ◇ Kanagawa, Japan

7Development Japan, Pfizer R&D Japan ◇ Tokyo, Japan

Deceased on May 22, 2017

受付日:2018年9月28日Received: September 28, 2018
受理日:2019年4月3日Accepted: April 3, 2019
発行日:2019年7月1日Published: July 1, 2019

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)

Key words: efficacy; pediatric; pulmonary arterial hypertension; safety; sildenafil

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