Journal Article

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)

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

2019

Overview

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 2 vs. − 0.31 ± 0.71 l/min/m 2 , 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 2 vs. − 0.45 ± 1.36 l/min/m 2 , 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 th of November 2014.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Aged / Ambrisentan / Antihypertensive Agents - administration & dosage / Blood pressure / Borderline pulmonary hypertension / Catheterization / Clinical trials / Cohort Studies / Comorbidity / Dosage and administration / Double-Blind Method / Drug therapy / Exercise / Exercise PH / Female / Heart catheterization / Humans / Hypertension / Hypertension, Pulmonary - diagnosis / Hypertension, Pulmonary - drug therapy / Hypertension, Pulmonary - epidemiology / Male / Medicine / Medicine & Public Health / Middle Aged / Mildly elevated mPAP / Orthopedics / Patient outcomes / Phenylpropionates - administration & dosage / Placebo-controlled / Prospective Studies / Pulmonary hypertension / Pyridazines - administration & dosage / Research Article / Rheumatology / Scleroderma (Disease) / Scleroderma, Systemic - diagnosis / Scleroderma, Systemic - drug therapy / Scleroderma, Systemic - epidemiology / Time-to-Treatment - trends / Treatment