Bosentan Improves Exercise Capacity in Adolescents and Adults After Fontan Operation: The TEMPO (Treatment With Endothelin Receptor Antagonist in Fontan Patients, a Randomized, Placebo-Controlled, Double-Blind Study Measuring Peak Oxygen Consumption) Study
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Bosentan Improves Exercise Capacity in Adolescents and Adults After Fontan Operation : The TEMPO (Treatment With Endothelin Receptor Antagonist in Fontan Patients, a Randomized, Placebo-Controlled, Double-Blind Study Measuring Peak Oxygen Consumption) Study. / Hebert, Anders; Mikkelsen, Ulla Ramer; Thilen, Ulf; Idorn, Lars; Jensen, Annette Schophuus; Nagy, Edit; Hanseus, Katarina; Sørensen, Keld E; Søndergård, Lars.
I: Circulation, Bind 130, Nr. 23, 2014, s. 2021-2030.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Bosentan Improves Exercise Capacity in Adolescents and Adults After Fontan Operation
T2 - The TEMPO (Treatment With Endothelin Receptor Antagonist in Fontan Patients, a Randomized, Placebo-Controlled, Double-Blind Study Measuring Peak Oxygen Consumption) Study
AU - Hebert, Anders
AU - Mikkelsen, Ulla Ramer
AU - Thilen, Ulf
AU - Idorn, Lars
AU - Jensen, Annette Schophuus
AU - Nagy, Edit
AU - Hanseus, Katarina
AU - Sørensen, Keld E
AU - Søndergård, Lars
N1 - © 2014 American Heart Association, Inc.
PY - 2014
Y1 - 2014
N2 - BACKGROUND: The Fontan procedure has improved survival in children with functionally univentricular hearts. With time, however, complications such as reduced exercise capacity are seen more frequently. Exercise intolerance is multifactorial, but pulmonary vascular resistance probably plays a crucial role. Elevated pulmonary vascular resistance has been associated with raised levels of endothelin-1, which are common both before and after Fontan operations. Treatment with endothelin-1 receptor antagonists could theoretically improve cardiopulmonary hemodynamics and exercise capacity. The aim of this study was therefore to examine the efficacy and safety of bosentan in Fontan patients.METHODS AND RESULTS: Seventy-five adolescents and adults were randomized 1:1 to 14 weeks of treatment with bosentan or placebo. Cardiopulmonary exercise test, functional class, blood samples, and quality-of-life questionnaires were evaluated at baseline and at the end of treatment. Sixty-nine patients (92%) completed the study. Peak oxygen consumption increased 2.0 mL·kg(-1)·min(-1) (from 28.7 to 30.7 mL·kg(-1)·min(-1)) in the bosentan group compared with 0.6 mL·kg(-1)·min(-1) (from 28.4 to 29.0 mL·kg(-1)·min(-1)) in the placebo group (P=0.02). Cardiopulmonary exercise test time increased by 0.48 minute (from 6.79 to 7.27 minutes) versus 0.08 minute (from 6.94 to 7.02 minutes; P=0.04). Nine bosentan-treated patients improved 1 functional class, whereas none improved in the placebo group (P=0.0085). Side effects were mild and occurred equally in both groups. No serious adverse effects were seen, and no patients had liver enzyme levels above the 3-fold upper limit.CONCLUSIONS: Bosentan improves exercise capacity, exercise time, and functional class in Fontan patients without serious adverse events or hepatotoxicity.CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01292551.
AB - BACKGROUND: The Fontan procedure has improved survival in children with functionally univentricular hearts. With time, however, complications such as reduced exercise capacity are seen more frequently. Exercise intolerance is multifactorial, but pulmonary vascular resistance probably plays a crucial role. Elevated pulmonary vascular resistance has been associated with raised levels of endothelin-1, which are common both before and after Fontan operations. Treatment with endothelin-1 receptor antagonists could theoretically improve cardiopulmonary hemodynamics and exercise capacity. The aim of this study was therefore to examine the efficacy and safety of bosentan in Fontan patients.METHODS AND RESULTS: Seventy-five adolescents and adults were randomized 1:1 to 14 weeks of treatment with bosentan or placebo. Cardiopulmonary exercise test, functional class, blood samples, and quality-of-life questionnaires were evaluated at baseline and at the end of treatment. Sixty-nine patients (92%) completed the study. Peak oxygen consumption increased 2.0 mL·kg(-1)·min(-1) (from 28.7 to 30.7 mL·kg(-1)·min(-1)) in the bosentan group compared with 0.6 mL·kg(-1)·min(-1) (from 28.4 to 29.0 mL·kg(-1)·min(-1)) in the placebo group (P=0.02). Cardiopulmonary exercise test time increased by 0.48 minute (from 6.79 to 7.27 minutes) versus 0.08 minute (from 6.94 to 7.02 minutes; P=0.04). Nine bosentan-treated patients improved 1 functional class, whereas none improved in the placebo group (P=0.0085). Side effects were mild and occurred equally in both groups. No serious adverse effects were seen, and no patients had liver enzyme levels above the 3-fold upper limit.CONCLUSIONS: Bosentan improves exercise capacity, exercise time, and functional class in Fontan patients without serious adverse events or hepatotoxicity.CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01292551.
KW - Adolescent
KW - Adult
KW - Child
KW - Child, Preschool
KW - Double-Blind Method
KW - Endothelin Receptor Antagonists
KW - Exercise Tolerance
KW - Female
KW - Fontan Procedure
KW - Hemodynamics
KW - Humans
KW - Infant
KW - Male
KW - Oxygen Consumption
KW - Placebos
KW - Postoperative Complications
KW - Receptor, Endothelin A
KW - Statistics, Nonparametric
KW - Sulfonamides
KW - Treatment Outcome
KW - Young Adult
U2 - 10.1161/CIRCULATIONAHA.113.008441
DO - 10.1161/CIRCULATIONAHA.113.008441
M3 - Journal article
C2 - 25446057
VL - 130
SP - 2021
EP - 2030
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 23
ER -
ID: 137359069