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

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 x m(2), 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.