Ivy Dunbar, Beghetti Maurice, Juaneda-Simian Ernesto, Miller Diane, Lukas Mary Ann, Ioannou Chris, Okour Malek, Narita Jun, Berger Rolf M F
Pediatric Cardiology, Children's Hospital, Colorado, Aurora, CO.
Pediatric Cardiology Unit, University Children's Hospital HUG, Pulmonary Hypertension Program HUG, Centre Universitaire Romand de Cardiologie et Chirurgie Cardiaque Pédiatrique (CURCCCP), University of Geneva, Geneva, Switzerland.
J Pediatr X. 2020 Sep 22;5:100055. doi: 10.1016/j.ympdx.2020.100055. eCollection 2020 Spring.
To assess the safety and efficacy of the endothelin receptor antagonist ambrisentan in pediatric pulmonary arterial hypertension (PAH).
In this open-label, phase IIb study, patients with PAH aged 8 to <18 years were randomized to low- or high-dose ambrisentan for 24 weeks. Most patients were receiving other PAH medication(s) that could not be changed during the trial. The primary outcome was safety (treatment-emergent adverse events [TEAEs]); secondary outcome was efficacy (including change from baseline to week 24 in 6-minute walking distance and World Health Organization functional class). Study staff were blinded to treatment. No statistical testing was performed.
Most of the 41 patients randomized (80%) experienced ≥1 TEAE; most were mild (22%) or moderate (49%) in severity (no difference between dose groups). Most common TEAEs were headache (24%), nausea (17%), abdominal pain (12%), and nasopharyngitis (12%). Eight patients had serious TEAEs; 2 were fatal (unrelated to study treatment). Improved 6-minute walking distance was observed from baseline to week 24: total mean (SD) change, +40.69 (84.58) meters; World Health Organization functional class was maintained or improved in 70% and 27% patients, respectively.
Ambrisentan was well tolerated; TEAEs were consistent with the adult safety profile. Efficacy was similar to previous findings in adult PAH; however, interpretation is limited by small sample size. Findings support a potentially similar benefit:risk profile in pediatric (8 to <18 years) and adult patients with PAH.
ClinicalTrials.gov: NCT01332331.
评估内皮素受体拮抗剂安立生坦治疗儿童肺动脉高压（PAH）的安全性和有效性。
在这项开放标签的IIb期研究中，8至<18岁的PAH患者被随机分为低剂量或高剂量安立生坦组，治疗24周。大多数患者在试验期间正在接受其他无法改变的PAH药物治疗。主要结局是安全性（治疗期间出现的不良事件[TEAE]）；次要结局是有效性（包括从基线到第24周6分钟步行距离和世界卫生组织功能分级的变化）。研究人员对治疗分组不知情。未进行统计学检验。
41例随机分组的患者中，大多数（80%）经历了≥1次TEAE；大多数为轻度（22%）或中度（49%）（剂量组间无差异）。最常见的TEAE是头痛（24%）、恶心（17%）、腹痛（12%）和鼻咽炎（12%）。8例患者发生严重TEAE；2例死亡（与研究治疗无关）。从基线到第24周，6分钟步行距离有所改善：总平均（标准差）变化为+40.69（84.58）米；分别有70%和27%的患者世界卫生组织功能分级维持不变或得到改善。
安立生坦耐受性良好；TEAE与成人安全性概况一致。有效性与先前成人PAH的研究结果相似；然而，由于样本量小，解释受到限制。研究结果支持儿童（8至<18岁）和成人PAH患者潜在的相似获益：风险概况。
ClinicalTrials.gov：NCT01332331。
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