Artículos de revistas
Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension
Fecha
2012Registro en:
PULMONARY PHARMACOLOGY & THERAPEUTICS, LONDON, v. 25, n. 1, supl. 1, Part 3, pp. 33-39, FEB, 2012
1094-5539
10.1016/j.pupt.2011.10.002
Autor
Sandoval, Julio
Torbicki, Adam
Souza, Rogerio
Ramirez, Alicia
Kurzyna, Marcin
Jardim, Carlos
Jerjes-Sanchez Diaz, Carlos
Teal, Simon A.
Hwang, Lie-Ju
Pulido, Tomas
Institución
Resumen
Objective: To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension (PAH). Background: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury. Methods: Before sitaxsentan withdrawal, this 18-week double-blind, placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily. The primary efficacy endpoint was change from baseline in 6-min walk distance (6MWD) at week 18. Changes in World Health Organization (WHO) functional class and time to clinical worsening (TTCW) were secondary endpoints. The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo. Results: Of 98 randomized patients, 61% were WHO functional class II at baseline. Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg; a strong placebo effect was observed. At week 18, WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo (P = 0.038); 0% versus 12% of patients deteriorated, respectively. TTCW was not significantly different for 100-mg sitaxsentan patients than placebo (P = 0.090). Adverse events (AEs) occurring more frequently with sitaxsentan (50 or 100 mg) included headache, peripheral edema, dizziness, nausea, extremity pain, and fatigue; most AEs were of mild or moderate severity. Conclusion: Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline. No patient receiving sitaxsentan 100 mg experienced clinical worsening; sitaxsentan was well tolerated. (C) 2011 Elsevier Ltd. All rights reserved.