eprintid: 10084993 rev_number: 31 eprint_status: archive userid: 608 dir: disk0/10/08/49/93 datestamp: 2019-11-07 14:28:25 lastmod: 2021-09-26 23:12:31 status_changed: 2019-11-07 14:28:25 type: article metadata_visibility: show creators_name: Pan, Z creators_name: Marra, AM creators_name: Benjamin, N creators_name: Eichstaedt, CA creators_name: Blank, N creators_name: Bossone, E creators_name: Cittadini, A creators_name: Coghlan, G creators_name: Denton, CP creators_name: Distler, O creators_name: Egenlauf, B creators_name: Fischer, C creators_name: Harutyunova, S creators_name: Xanthouli, P creators_name: Lorenz, H-M creators_name: Grünig, E title: 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) ispublished: pub subjects: RFH divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G90 keywords: Ambrisentan, Borderline pulmonary hypertension, Exercise PH, Mildly elevated mPAP, Placebo-controlled, Treatment note: © 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. abstract: 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. date: 2019-10-26 date_type: published official_url: https://doi.org/10.1186/s13075-019-1981-0 oa_status: green full_text_type: pub pmcid: PMC6815440 language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1714909 doi: 10.1186/s13075-019-1981-0 pii: 10.1186/s13075-019-1981-0 lyricists_name: Denton, Christopher lyricists_id: CPDEN87 actors_name: Nonhebel, Lucinda actors_id: LNONH33 actors_role: owner full_text_status: public publication: Arthritis Research and Therapy volume: 21 article_number: 217 event_location: England issn: 1478-6362 citation: Pan, Z; Marra, AM; Benjamin, N; Eichstaedt, CA; Blank, N; Bossone, E; Cittadini, A; ... Grünig, E; + view all <#> Pan, Z; Marra, AM; Benjamin, N; Eichstaedt, CA; Blank, N; Bossone, E; Cittadini, A; Coghlan, G; Denton, CP; Distler, O; Egenlauf, B; Fischer, C; Harutyunova, S; Xanthouli, P; Lorenz, H-M; Grünig, E; - view fewer <#> (2019) 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). Arthritis Research and Therapy , 21 , Article 217. 10.1186/s13075-019-1981-0 <https://doi.org/10.1186/s13075-019-1981-0>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10084993/1/Denton_OA_s13075-019-1981-0.pdf