Dunbar Ivy, Maurice Beghetti, Ernesto Juaneda‑Simian, Ramiya Ravindranath, Mary Ann Lukas, Sandra Machlitt‑Northen, Nicola Scott, Jun Narita, Rolf M. F. Berger
Children’s Hospital Colorado. University Children’s Hospital HUG and University of Geneva. Hospital de Niños de la Santísma Trinidad. Glaxo-Smith-Kline. Osaka University Graduate School of Medicine. Beatrix Children’s Hospital, University Medical Center Groningen and University of Groningen.
United States, Switzerland, Argentina, India, United Kingdom, Japan and Netherlands
European Journal of Pediatrics
Eur J Pediatr 2024;
DOI: 10.1007/s00431-024-05446-1
Abstract
This open-label, extension study assessed long-term safety, tolerability, and efficacy of ambrisentan in a pediatric population (age 8- < 18 years) with pulmonary arterial hypertension (PAH). Following completion of a 6-month, randomized study, participants entered the long-term extension at individualized ambrisentan dosages (2.5/5/7.5 or 10 mg/day). Safety assessments included adverse events (AEs), AEs of special interest, and serious AEs (SAEs); efficacy outcomes included 6-min walking distance (6MWD) and World Health Organization functional class (WHO FC). Thirty-eight of 41 (93%) randomized study participants entered the extension; 21 (55%) completed (reaching age 18 years). Most participants received concomitant phosphodiesterase-5 inhibitors (n = 25/38, 66%). Median ambrisentan exposure was 3.5 years. Most participants experienced ≥ 1 AE (n = 34/38, 89%), and 21 (55%) experienced SAEs, most commonly worsening PAH (n = 3/38, 8%), acute cardiac failure, pneumonia, or anemia (n = 2/38; 5% each); none considered ambrisentan-related. Seven participants (18%) died, with recorded reasons (MedDRA preferred term): cardiac failure (n = 2), PAH (n = 2), COVID-19 (n = 1), acute right ventricular failure (n = 1), and failure to thrive (n = 1); median time to death: 5.2 years. Anemia and hepatotoxicity AEs were generally mild to moderate and did not require ambrisentan dose adjustment. Assessed at study end in 29 participants (76%), mean 6MWD improved by 17% (standard deviation: 34.3%), and all (29/29, 100%) had improved or unchanged WHO FC. Conclusion: Long-term weight-based ambrisentan dosing, alone or combined with other PAH therapies in children with PAH aged 8- < 18 years, exhibited tolerability and clinical improvements consistent with prior randomized study results.
Category
Class I. Idiopathic Pulmonary Hypertension
Class I. Heritable Pulmonary Hypertension
Class I. Pulmonary Hypertension Associated with Congenital Cardiovascular Disease
Class I. Pulmonary Hypertension Associated with Connective Tissue Disease
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes