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.