Evaluation of Macitentan in Patients With Eisenmenger Syndrome.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_2B3253EE0026
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evaluation of Macitentan in Patients With Eisenmenger Syndrome.
Journal
Circulation
Author(s)
Gatzoulis M.A., Landzberg M., Beghetti M., Berger R.M., Efficace M., Gesang S., He J., Papadakis K., Pulido T., Galiè N.
Working group(s)
MAESTRO Study Investigators
ISSN
1524-4539 (Electronic)
ISSN-L
0009-7322
Publication state
Published
Issued date
02/01/2019
Peer-reviewed
Oui
Volume
139
Number
1
Pages
51-63
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome.
Patients with Eisenmenger syndrome aged ≥12 years and in World Health Organization functional class II-III were randomized 1:1 to placebo or macitentan 10 mg once daily for 16 weeks. Patients with complex cardiac defects, Down syndrome and background PAH therapy were eligible. The primary end point was change from baseline to week 16 in 6-minute walk distance. Secondary end points included change from baseline to week 16 in World Health Organization functional class. Exploratory end points included NT-proBNP (N-terminal pro-B-type natriuretic peptide) at end of treatment expressed as a percentage of baseline. In a hemodynamic substudy, exploratory end points included pulmonary vascular resistance index (PVRi) at week 16 as a percentage of baseline.
Two hundred twenty six patients (macitentan n=114; placebo n=112) were randomized. At baseline, 60% of patients were in World Health Organization functional class II and 27% were receiving phosphodiesterase type-5 inhibitors. At week 16, the mean change from baseline in 6-minute walk distance was 18.3 m and 19.7 m in the macitentan and placebo groups (least-squares mean difference, -4.7 m; 95% confidence limit (CL), -22.8, 13.5; P=0.612). World Health Organization functional class improved from baseline to week 16 in 8.8% and 14.3% of patients in the macitentan and placebo groups (odds ratio, 0.53; 95% CL, 0.23, 1.24). NT-proBNP levels decreased with macitentan versus placebo (ratio of geometric means, 0.80; 95% CL, 0.68, 0.94). In the hemodynamic substudy (n=39 patients), macitentan decreased PVRi compared with placebo (ratio of geometric means, 0.87; 95% CL, 0.73, 1.03). The most common adverse events with macitentan versus placebo were headache (11.4 versus 4.5%) and upper respiratory tract infection (9.6 versus 6.3%); a hemoglobin decrease from baseline of ≥2 g/dL occurred in 36.0% versus 8.9% of patients. Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment and 1 patient died (macitentan group).
Macitentan did not show superiority over placebo on the primary end point of change from baseline to week 16 in exercise capacity in patients with Eisenmenger syndrome.
URL: https://www.clinicaltrials.gov . Unique identifier: NCT01743001.
Keywords
Adolescent, Adult, Aged, Aged, 80 and over, Antihypertensive Agents/adverse effects, Antihypertensive Agents/therapeutic use, Biomarkers/blood, Child, Double-Blind Method, Down Syndrome/complications, Eisenmenger Complex/complications, Eisenmenger Complex/diagnostic imaging, Eisenmenger Complex/physiopathology, Endothelin Receptor Antagonists/adverse effects, Endothelin Receptor Antagonists/therapeutic use, Exercise Tolerance/drug effects, Female, Hemodynamics/drug effects, Humans, Hypertension, Pulmonary/diagnostic imaging, Hypertension, Pulmonary/drug therapy, Hypertension, Pulmonary/etiology, Hypertension, Pulmonary/physiopathology, Male, Middle Aged, Natriuretic Peptide, Brain/blood, Peptide Fragments/blood, Pulmonary Artery/drug effects, Pulmonary Artery/physiopathology, Pyrimidines/adverse effects, Pyrimidines/therapeutic use, Recovery of Function, Sulfonamides/adverse effects, Sulfonamides/therapeutic use, Time Factors, Treatment Outcome, Walk Test, Young Adult, Down syndrome, Eisenmenger syndrome, congenital heart disease, endothelin receptor antagonist, macitentan, pulmonary arterial hypertension
Pubmed
Web of science
Open Access
Yes
Create date
14/01/2019 9:43
Last modification date
16/06/2020 5:21
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