TY  - JOUR
TI  - Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study)
VL  - 21
AV  - public
Y1  - 2019/10/26/
N1  - © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/ 1.0/) applies to the data made available in this article, unless otherwise stated.
ID  - discovery10084993
N2  - OBJECTIVE: The objective of this randomized, placebo-controlled, double-blind, parallel group, trial was to assess the effect of ambrisentan on mean pulmonary arterial pressure (mPAP) in patients with systemic sclerosis (SSc) and mildly elevated pulmonary hypertension (PH). METHODS: Thirty-eight SSc patients with mildly elevated mPAP at rest between 21 and 24?mmHg and/or >?30?mmHg during low-dose exercise were randomly assigned to treatment with either ambrisentan 5-10?mg/day or placebo. Right heart catheterization and further clinical parameters were assessed at baseline and after 6?months. The primary endpoint was the difference of mPAP change at rest between groups. RESULTS: After 6?months, the two groups did not differ in the primary endpoint (ambrisentan mPAP -?1?±?6.4?mmHg vs. placebo -?0.73?±?3.59?mmHg at rest, p?=?0.884). However, three patients from the placebo group but none of the ambrisentan group progressed to SSc-associated pulmonary arterial hypertension. Furthermore, ambrisentan treatment showed significant improvements in the secondary endpoints cardiac index (CI) and pulmonary vascular resistance (PVR) at rest (CI 0.36?±?0.66?l/min/m2 vs. -?0.31?±?0.71?l/min/m2, p?=?0.010; PVR -?0.70?±?0.78 WU vs. 0.01?±?0.71 WU, p?=?0.012) and during exercise (CI 0.7?±?0.81?l/min/m2 vs. -?0.45?±?1.36?l/min/m2, p?=?0.015; PVR -?0.84?±?0.48 WU vs. -?0.0032?±?0.34 WU, p?<?0.0001). CONCLUSION: This is the first randomized, double-blind, placebo-controlled study testing the effect of ambrisentan in patients with mildly elevated mPAP and/or exercise PH. The primary endpoint change in mPAP did only tendentially improve in the ambrisentan group, but the significant improvement of other hemodynamic parameters points to a possible benefit of ambrisentan and will be helpful to design future trials. TRIAL REGISTRATION: www.ClinicalTrials.gov, unique identifier NCT: NCT02290613 , registered 14th of November 2014.
SN  - 1478-6362
UR  - https://doi.org/10.1186/s13075-019-1981-0
JF  - Arthritis Research and Therapy
KW  - Ambrisentan
KW  -  Borderline pulmonary hypertension
KW  -  Exercise PH
KW  -  Mildly elevated mPAP
KW  -  Placebo-controlled
KW  -  Treatment
A1  - Pan, Z
A1  - Marra, AM
A1  - Benjamin, N
A1  - Eichstaedt, CA
A1  - Blank, N
A1  - Bossone, E
A1  - Cittadini, A
A1  - Coghlan, G
A1  - Denton, CP
A1  - Distler, O
A1  - Egenlauf, B
A1  - Fischer, C
A1  - Harutyunova, S
A1  - Xanthouli, P
A1  - Lorenz, H-M
A1  - Grünig, E
ER  -