Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial

Chest. 2014 Apr;145(4):810-817. doi: 10.1378/chest.13-1766.

Abstract

Background: Sarcoidosis-associated pulmonary hypertension (SAPH) is a common problem in patients with persistent dyspneic sarcoidosis. The objective of this study was to determine the effect of bosentan therapy on pulmonary arterial hemodynamics in patients with SAPH.

Methods: This 16-week study was a double-blind, placebo-controlled trial of either bosentan or placebo in patients with SAPH confirmed by right-sided heart catheterization. Patients were enrolled from multiple academic centers specializing in sarcoidosis care. They were stable on sarcoidosis therapy and were receiving no therapy for pulmonary hypertension. The cohort was randomized two to one to receive bosentan at a maximal dose of 125 mg or placebo bid for 16 weeks. Pulmonary function studies, 6-min walk test, and right-sided heart hemodynamics, including pulmonary artery mean pressure and pulmonary vascular resistance (PVR), were performed before and after 16 weeks of therapy.

Results: Thirty-five patients completed 16 weeks of therapy (23 treated with bosentan, 12 with placebo). For those treated with bosentan, repeat hemodynamic studies at 16 weeks demonstrated a significant mean±SD fall in PA mean pressure (-4±6.6 mm Hg, P=.0105) and PVR (-1.7±2.75 Wood units, P=.0104). For the patients treated with placebo, there was no significant change in either PA mean pressure (1±3.7 mm Hg, P>.05) or PVR (0.1±1.42 Wood units, P>.05). There was no significant change in 6-min walk distance for either group. Two patients treated with bosentan required an increase of supplemental oxygen by >2 L after 16 weeks of therapy.

Conclusions: This study demonstrated that bosentan significantly improved pulmonary hemodynamics in patients with SAPH.

Trial registry: ClinicalTrials.gov; No: NCT00581607; URL: www.clinicaltrials.gov.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / therapeutic use*
  • Bosentan
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / etiology
  • Male
  • Middle Aged
  • Sarcoidosis, Pulmonary / complications
  • Sulfonamides / therapeutic use*

Substances

  • Antihypertensive Agents
  • Sulfonamides
  • Bosentan

Associated data

  • ClinicalTrials.gov/NCT00581607