{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:46:03Z","timestamp":1793727963261,"version":"4.6.1"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":261,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005075","name":"Universitair Medisch Centrum Groningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005075","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015340","name":"Bayer Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015340","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010174","name":"University of Colorado","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010174","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005646","name":"Actelion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007150","name":"United Therapeutics Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["112529"],"award-info":[{"award-number":["112529"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pediatrics: X"],"published-print":{"date-parts":[[2020]]},"DOI":"10.1016\/j.ympdx.2020.100055","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T17:29:57Z","timestamp":1600795797000},"page":"100055","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["A Randomized Study of Safety and Efficacy of Two Doses of Ambrisentan to Treat Pulmonary Arterial Hypertension in Pediatric Patients Aged 8 Years up to 18 Years"],"prefix":"10.1016","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2541-3402","authenticated-orcid":false,"given":"Dunbar","family":"Ivy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Beghetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Juaneda-Simian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Ann","family":"Lukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Ioannou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malek","family":"Okour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Narita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.F.","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ympdx.2020.100055_bib1","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1136\/hrt.2009.182378","article-title":"Childhood idiopathic pulmonary arterial hypertension: a national cohort study","volume":"96","author":"Moledina","year":"2010","journal-title":"Heart"},{"key":"10.1016\/j.ympdx.2020.100055_bib2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/eurheartj\/ehv317","volume":"37","author":"Galie","year":"2016","journal-title":"Eur Heart J"},{"key":"10.1016\/j.ympdx.2020.100055_bib3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1750-1172-8-97","article-title":"Pulmonary arterial hypertension","volume":"8","author":"Montani","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"10.1016\/j.ympdx.2020.100055_bib4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1183\/09031936.00056110","article-title":"Pulmonary arterial hypertension: a comparison between children and adults","volume":"37","author":"Barst","year":"2011","journal-title":"Eur Respir J"},{"key":"10.1016\/j.ympdx.2020.100055_bib5","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1164\/rccm.201406-1052OC","article-title":"Assessing pulmonary hypertensive vascular disease in childhood. Data from the Spanish registry","volume":"190","author":"del Cerro Marin","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.ympdx.2020.100055_bib6","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1161\/CIRCULATIONAHA.110.969584","article-title":"Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005","volume":"124","author":"van Loon","year":"2011","journal-title":"Circulation"},{"key":"10.1016\/j.ympdx.2020.100055_bib7","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1086\/681226","article-title":"Trends in pediatric pulmonary hypertension-related hospitalizations in the United States from 2000-2009","volume":"5","author":"Frank","year":"2015","journal-title":"Pulm Circ"},{"key":"10.1016\/j.ympdx.2020.100055_bib8","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1542\/peds.2014-3834","article-title":"Trends in Hospitalization for Pediatric Pulmonary Hypertension","volume":"136","author":"Maxwell","year":"2015","journal-title":"Pediatrics"},{"key":"10.1016\/j.ympdx.2020.100055_bib9","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4103\/0022-3859.159421","article-title":"Sildenafil in pediatric pulmonary arterial hypertension","volume":"61","author":"Dhariwal","year":"2015","journal-title":"J Postgrad Med"},{"key":"10.1016\/j.ympdx.2020.100055_bib10","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0140-6736(11)61621-8","article-title":"Clinical features of paediatric pulmonary hypertension: a registry study","volume":"379","author":"Berger","year":"2012","journal-title":"Lancet"},{"key":"10.1016\/j.ympdx.2020.100055_bib11","doi-asserted-by":"crossref","first-page":"1801916","DOI":"10.1183\/13993003.01916-2018","article-title":"Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management","volume":"53","author":"Rosenzweig","year":"2019","journal-title":"Eur Respir J"},{"key":"10.1016\/j.ympdx.2020.100055_bib12","doi-asserted-by":"crossref","first-page":"e011306","DOI":"10.1161\/JAHA.118.011306","article-title":"New strategies for the conduct of clinical trials in pediatric pulmonary arterial hypertension: outcome of a multistakeholder meeting with patients, academia, industry, and regulators, held at the European Medicines Agency on Monday, June 12, 2017","volume":"8","author":"Ollivier","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.ympdx.2020.100055_bib13","series-title":"Revatio (sildenafil) Summary of Product Characteristics","year":"2019"},{"key":"10.1016\/j.ympdx.2020.100055_bib15","series-title":"TRACLEER (bosentan) Prescribing Information","year":"2017"},{"key":"10.1016\/j.ympdx.2020.100055_bib16","series-title":"Tracleer (bosentan) Summary of Product Characteristics","year":"2019"},{"key":"10.1016\/j.ympdx.2020.100055_bib17","series-title":"FLOLAN (epoprostenol) Prescribing Information","year":"2017"},{"key":"10.1016\/j.ympdx.2020.100055_bib18","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/14779072.2019.1576523","article-title":"Diagnosis and treatment of pediatric pulmonary arterial hypertension","volume":"17","author":"Farhat","year":"2019","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"10.1016\/j.ympdx.2020.100055_bib19","doi-asserted-by":"crossref","first-page":"ii67","DOI":"10.1136\/heartjnl-2015-309103","article-title":"Treatment of children with pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK","volume":"102","author":"Hansmann","year":"2016","journal-title":"Heart"},{"key":"10.1016\/j.ympdx.2020.100055_bib20","series-title":"Volibris - Summary of Product Characteristics","year":"2008"},{"key":"10.1016\/j.ympdx.2020.100055_bib21","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1161\/CIRCULATIONAHA.107.742510","article-title":"Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2","volume":"117","author":"Galie","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.ympdx.2020.100055_bib22","first-page":"401","article-title":"Ambrisentan for the treatment of pulmonary arterial hypertension: improving outcomes","volume":"7","author":"Elshaboury","year":"2013","journal-title":"Patient Prefer Adherence"},{"key":"10.1016\/j.ympdx.2020.100055_bib23","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/j.jacc.2009.07.033","article-title":"Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension","volume":"54","author":"Oudiz","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.ympdx.2020.100055_bib24","doi-asserted-by":"crossref","first-page":"253","DOI":"10.2147\/VHRM.S133921","article-title":"Endothelin-receptor antagonists in the management of pulmonary arterial hypertension: where do we stand?","volume":"14","author":"Correale","year":"2018","journal-title":"Vasc Health Risk Manag"},{"key":"10.1016\/j.ympdx.2020.100055_bib25","series-title":"EMEA-000434-PIP01-08-M05","year":"2019"},{"key":"10.1016\/j.ympdx.2020.100055_bib26","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"Declaration of Helsinki: ethical principles\u00a0for medical research involving human subjects","volume":"310","author":"World Medical Association","year":"2013","journal-title":"JAMA"},{"key":"10.1016\/j.ympdx.2020.100055_bib27","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1016\/j.jacc.2009.04.012","article-title":"Updated clinical classification of pulmonary hypertension","volume":"54","author":"Simonneau","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.ympdx.2020.100055_bib28","series-title":"LETAIRIS (ambrisentan) Prescribing Information","year":"2019"},{"key":"10.1016\/j.ympdx.2020.100055_bib29","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1056\/NEJMoa1413687","article-title":"Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension","volume":"373","author":"Galie","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ympdx.2020.100055_bib30","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s40256-018-0272-5","article-title":"Pulmonary arterial hypertension: combination therapy in practice","volume":"18","author":"Burks","year":"2018","journal-title":"Am J Cardiovasc Drugs"},{"key":"10.1016\/j.ympdx.2020.100055_bib31","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/ppul.22555","article-title":"Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension","volume":"48","author":"Takatsuki","year":"2013","journal-title":"Pediatr Pulmonol"},{"key":"10.1016\/j.ympdx.2020.100055_bib32","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S0009-9236(03)00005-5","article-title":"Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension","volume":"73","author":"Barst","year":"2003","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.ympdx.2020.100055_bib33","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1056\/NEJMoa012212","article-title":"Bosentan therapy for pulmonary arterial hypertension","volume":"346","author":"Rubin","year":"2002","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ympdx.2020.100055_bib34","series-title":"Opsumit (macitentan) Annex I: Summary of Product Characteristics","year":"2013"},{"key":"10.1016\/j.ympdx.2020.100055_bib35","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2147\/DHPS.S173050","article-title":"Safety and tolerability of macitentan in the management of pulmonary arterial hypertension: an update","volume":"11","author":"Wong","year":"2019","journal-title":"Drug Healthc Patient Saf"},{"key":"10.1016\/j.ympdx.2020.100055_bib36","doi-asserted-by":"crossref","first-page":"271","DOI":"10.5694\/mja16.00468","article-title":"Update on pharmacotherapy for pulmonary hypertension","volume":"205","author":"Prior","year":"2016","journal-title":"Med J Aust"},{"key":"10.1016\/j.ympdx.2020.100055_bib37","series-title":"Brain weight effect of ambrisentan in juvenile rats associated with breathing sounds, apnea and sustained hypoxemia","author":"Laffan","year":"2019"},{"key":"10.1016\/j.ympdx.2020.100055_bib38","doi-asserted-by":"crossref","first-page":"249","DOI":"10.5152\/akd.2015.5834","article-title":"Six-minute walk test in pulmonary arterial hypertension","volume":"15","author":"Demir","year":"2015","journal-title":"Anatol J Cardiol"},{"key":"10.1016\/j.ympdx.2020.100055_bib39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ijcard.2015.08.155","article-title":"Six-minute walking distance and decrease in oxygen saturation during the six-minute walk test in pediatric pulmonary arterial hypertension","volume":"202","author":"Douwes","year":"2016","journal-title":"Int J Cardiol"},{"key":"10.1016\/j.ympdx.2020.100055_bib40","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1007\/s00246-017-1575-z","article-title":"Six-minute walk test in evaluation of children with pulmonary arterial hypertension","volume":"38","author":"Zuk","year":"2017","journal-title":"Pediatr Cardiol"},{"key":"10.1016\/j.ympdx.2020.100055_bib41","doi-asserted-by":"crossref","first-page":"D22","DOI":"10.1016\/j.jacc.2013.10.027","article-title":"Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology","volume":"62","author":"Vonk-Noordegraaf","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.ympdx.2020.100055_bib42","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1183\/09031936.00016006","article-title":"NT-proBNP reflects right ventricular structure and function in pulmonary hypertension","volume":"28","author":"Gan","year":"2006","journal-title":"Eur Respir J"},{"key":"10.1016\/j.ympdx.2020.100055_bib43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ijcard.2008.03.009","article-title":"Prognostic value of B-type natriuretic peptide in children with pulmonary hypertension","volume":"135","author":"Lammers","year":"2009","journal-title":"Int J Cardiol"},{"key":"10.1016\/j.ympdx.2020.100055_bib44","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1378\/chest.08-0187","article-title":"Brain natriuretic peptide levels in managing pediatric patients with pulmonary arterial hypertension","volume":"135","author":"Bernus","year":"2009","journal-title":"Chest"},{"key":"10.1016\/j.ympdx.2020.100055_bib45","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1183\/09031936.00030414","article-title":"Identification of treatment goals in paediatric pulmonary arterial hypertension","volume":"44","author":"Ploegstra","year":"2014","journal-title":"Eur Respir J"},{"key":"10.1016\/j.ympdx.2020.100055_bib46","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1161\/CIRCULATIONAHA.110.016667","article-title":"A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension","volume":"125","author":"Barst","year":"2012","journal-title":"Circulation"},{"key":"10.1016\/j.ympdx.2020.100055_bib47","series-title":"The management of clinical trials","article-title":"Challenges in Paediatric Clinical Trials: How to Make It Feasible","author":"Chiaruttini","year":"2018"}],"container-title":["The Journal of Pediatrics: X"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2590042020300367?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2590042020300367?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T04:40:42Z","timestamp":1778906442000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2590042020300367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":46,"alternative-id":["S2590042020300367"],"URL":"https:\/\/doi.org\/10.1016\/j.ympdx.2020.100055","relation":{},"ISSN":["2590-0420"],"issn-type":[{"value":"2590-0420","type":"print"}],"subject":[],"published":{"date-parts":[[2020]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Randomized Study of Safety and Efficacy of Two Doses of Ambrisentan to Treat Pulmonary Arterial Hypertension in Pediatric Patients Aged 8 Years up to 18 Years","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pediatrics: X","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ympdx.2020.100055","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 GlaxoSmithKline. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"100055"}}