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Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks: A Post-hoc Analysis From the FUTURE 3 Study

FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion (FUTURE) 3 was a 24-week open-label, prospective, and randomized phase 3 study that assessed the pharmacokinetics of bosentan 2 mg/kg b.i.d. or t.i.d. in children with pulmonary arterial hypertension (PAH). We report findings from a post-hoc...

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Autores principales: Beghetti, Maurice, Berger, Rolf M. F., Bonnet, Damien, Grill, Simon, Lesage, Catherine, Lemarie, Jean-Christophe, Ivy, D. Dunbar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242164/
https://www.ncbi.nlm.nih.gov/pubmed/34222150
http://dx.doi.org/10.3389/fped.2021.681538
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author Beghetti, Maurice
Berger, Rolf M. F.
Bonnet, Damien
Grill, Simon
Lesage, Catherine
Lemarie, Jean-Christophe
Ivy, D. Dunbar
author_facet Beghetti, Maurice
Berger, Rolf M. F.
Bonnet, Damien
Grill, Simon
Lesage, Catherine
Lemarie, Jean-Christophe
Ivy, D. Dunbar
author_sort Beghetti, Maurice
collection PubMed
description FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion (FUTURE) 3 was a 24-week open-label, prospective, and randomized phase 3 study that assessed the pharmacokinetics of bosentan 2 mg/kg b.i.d. or t.i.d. in children with pulmonary arterial hypertension (PAH). We report findings from a post-hoc analysis that explored the prognostic value of echocardiographic changes during FUTURE 3 in relation to clinical outcomes observed during the 24-week core study and 48-week extension. Patients aged ≥3 months to <12 years (n = 64) received oral doses of bosentan 2 mg/kg b.i.d. or t.i.d. (1:1) for 24 weeks, after which they were eligible to enter the extension with continued bosentan administration. Echocardiographic evaluations were performed at baseline, Week 12, and 24 of the core study via central reading, and analyzed post-hoc for correlation with clinical outcomes (time to PAH worsening, time to death, and vital status). Sixty-four patients were randomized in the core study [median (IQR) age 3.8 (1.7–7.8) years]; and 58 patients (90.6%) entered the 48-week extension. Most of the patients (68.8%) were receiving ≥1 PAH medication at baseline. Echocardiographic changes during the core study were small but with high variability. There were statistically significant associations at Week 24 between worsening of the parameters, systolic left ventricular eccentricity index (LVEIS) and E/A ratio mitral valve flow, and the outcomes of time to death and time to PAH worsening. Additional studies that utilize simple and reproducible echocardiographic assessments are needed to confirm these findings and subsequently identify potential treatment goals in pediatric PAH.
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spelling pubmed-82421642021-07-01 Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks: A Post-hoc Analysis From the FUTURE 3 Study Beghetti, Maurice Berger, Rolf M. F. Bonnet, Damien Grill, Simon Lesage, Catherine Lemarie, Jean-Christophe Ivy, D. Dunbar Front Pediatr Pediatrics FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion (FUTURE) 3 was a 24-week open-label, prospective, and randomized phase 3 study that assessed the pharmacokinetics of bosentan 2 mg/kg b.i.d. or t.i.d. in children with pulmonary arterial hypertension (PAH). We report findings from a post-hoc analysis that explored the prognostic value of echocardiographic changes during FUTURE 3 in relation to clinical outcomes observed during the 24-week core study and 48-week extension. Patients aged ≥3 months to <12 years (n = 64) received oral doses of bosentan 2 mg/kg b.i.d. or t.i.d. (1:1) for 24 weeks, after which they were eligible to enter the extension with continued bosentan administration. Echocardiographic evaluations were performed at baseline, Week 12, and 24 of the core study via central reading, and analyzed post-hoc for correlation with clinical outcomes (time to PAH worsening, time to death, and vital status). Sixty-four patients were randomized in the core study [median (IQR) age 3.8 (1.7–7.8) years]; and 58 patients (90.6%) entered the 48-week extension. Most of the patients (68.8%) were receiving ≥1 PAH medication at baseline. Echocardiographic changes during the core study were small but with high variability. There were statistically significant associations at Week 24 between worsening of the parameters, systolic left ventricular eccentricity index (LVEIS) and E/A ratio mitral valve flow, and the outcomes of time to death and time to PAH worsening. Additional studies that utilize simple and reproducible echocardiographic assessments are needed to confirm these findings and subsequently identify potential treatment goals in pediatric PAH. Frontiers Media S.A. 2021-06-16 /pmc/articles/PMC8242164/ /pubmed/34222150 http://dx.doi.org/10.3389/fped.2021.681538 Text en Copyright © 2021 Beghetti, Berger, Bonnet, Grill, Lesage, Lemarie and Ivy. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Beghetti, Maurice
Berger, Rolf M. F.
Bonnet, Damien
Grill, Simon
Lesage, Catherine
Lemarie, Jean-Christophe
Ivy, D. Dunbar
Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks: A Post-hoc Analysis From the FUTURE 3 Study
title Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks: A Post-hoc Analysis From the FUTURE 3 Study
title_full Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks: A Post-hoc Analysis From the FUTURE 3 Study
title_fullStr Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks: A Post-hoc Analysis From the FUTURE 3 Study
title_full_unstemmed Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks: A Post-hoc Analysis From the FUTURE 3 Study
title_short Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks: A Post-hoc Analysis From the FUTURE 3 Study
title_sort echocardiographic changes and long-term clinical outcomes in pediatric patients with pulmonary arterial hypertension treated with bosentan for 72 weeks: a post-hoc analysis from the future 3 study
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242164/
https://www.ncbi.nlm.nih.gov/pubmed/34222150
http://dx.doi.org/10.3389/fped.2021.681538
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