Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: Open-label pilot study

Robyn J. Barst*, Stuart Rich, Allison Widlitz, Evelyn M. Horn, Vallerie McLaughlin, Joyce McFarlin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

215 Scopus citations

Abstract

Study objectives: To evaluate the safety and efficacy of sitaxsentan, an endothelin-A receptor antagonist, in a 12-week, open-label trial of patients with pulmonary arterial hypertension (PAH). Patients: Six children and 14 adults with New York Heart Association (NYHA) functional class II, III, or IV primary pulmonary hypertension or PAH associated with either congenital systemic-to-pulmonary shunts or collagen vascular disease were enrolled. Measurements: Sitaxsentan was administered orally at 100 to 500 mg bid for 12 weeks. Cardiopulmonary hemodynamics via cardiac catheterization were obtained at baseline and week 12. Six-minute walk test distance was measured at baseline, week 6, and week 12. Results: Sitaxsentan treatment resulted in significant improvement in exercise capacity as assessed by the 6-min walk distance (baseline [mean ± SD], 466 ± 132 m; week 12, 515 ± 141 m, n = 20, p = 0.006). Mean pulmonary artery pressure and pulmonary vascular resistance index also improved (63 ± 20 to 52 ± 22 mm Hg, n = 17, p = 0.0002; and 20 ± 11 to 14 ± 13 U × m2, n = 17, p = 0.008, respectively). Serious adverse events included two cases of acute hepatitis (fatal in one patient). Conclusions: Patients with NYHA functional class II, III, or IV PAH showed a significant improvement in exercise capacity and cardiopulmonary hemodynamics over a 12-week period of treatment with sitaxsentan, an endothelin-A receptor antagonist. Further investigation is warranted to evaluate the safety and efficacy of sitaxsentan in patients with PAH.

Original languageEnglish (US)
Pages (from-to)1860-1868
Number of pages9
JournalCHEST
Volume121
Issue number6
DOIs
StatePublished - Jun 2002

Keywords

  • Clinical trials
  • Endothelin
  • Hypertension, pulmonary
  • Pulmonary heart disease

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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