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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)


Pan, Zixuan; Marra, Alberto M; Benjamin, Nicola; Eichstaedt, Christina A; Blank, Norbert; Bossone, Eduardo; Cittadini, Antonio; Coghlan, Gerry; Denton, Christopher P; Distler, Oliver; Egenlauf, Benjamin; Fischer, Christine; Harutyunova, Satenik; Xanthouli, Panagiota; Lorenz, Hanns-Martin; Grünig, Ekkehard (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 & Therapy, 21(1):217.

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/m vs. - 0.31 ± 0.71 l/min/m, 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/m vs. - 0.45 ± 1.36 l/min/m, 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 14 of November 2014.

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/m vs. - 0.31 ± 0.71 l/min/m, 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/m vs. - 0.45 ± 1.36 l/min/m, 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 14 of November 2014.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Rheumatology
Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:26 October 2019
Deposited On:08 Nov 2019 13:22
Last Modified:13 May 2020 23:14
Publisher:BioMed Central
ISSN:1478-6354
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s13075-019-1981-0
PubMed ID:31655622

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