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)

Zixuan Pan, Alberto M. Marra, Nicola Benjamin, Christina A. Eichstaedt, Norbert Blank, Eduardo Bossone, Antonio Cittadini, Gerry Coghlan, Christopher P. Denton, Oliver Distler, Benjamin Egenlauf, Christine Fischer, Satenik Harutyunova, Panagiota Xanthouli, Hanns Martin Lorenz, Ekkehard Grünig

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number217
JournalArthritis Research and Therapy
Volume21
Issue number1
DOIs
Publication statusPublished - Oct 26 2019

Keywords

  • Ambrisentan
  • Borderline pulmonary hypertension
  • Exercise PH
  • Mildly elevated mPAP
  • Placebo-controlled
  • Treatment

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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