title: Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension.
abstract: 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  Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury.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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Heart Institute, Mexico City, Mexico. sandovalzarate@prodigy.net.mx
authors.forename: Julio
authors.initials: J
authors.lastname: Sandoval
authors.forename: Adam
authors.initials: A
authors.lastname: Torbicki
authors.forename: Rogerio
authors.initials: R
authors.lastname: Souza
authors.forename: Alicia
authors.initials: A
authors.lastname: Ramírez
authors.forename: Marcin
authors.initials: M
authors.lastname: Kurzyna
authors.forename: Carlos
authors.initials: C
authors.lastname: Jardim
authors.forename: Carlos
authors.initials: C
authors.lastname: Jerjes-Sánchez Díaz
authors.forename: Simon A
authors.initials: SA
authors.lastname: Teal
authors.forename: Lie-Ju
authors.initials: LJ
authors.lastname: Hwang
authors.forename: Tomas
authors.initials: T
authors.lastname: Pulido
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004417:Dyspnea / Q000503:physiopathology; D065128:Endothelin Receptor Antagonists; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D057194:Intention to Treat Analysis; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D018401:Sample Size; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D055815:Young Adult
chemical_list: D065128:Endothelin Receptor Antagonists; D007555:Isoxazoles; D013876:Thiophenes; C106276:sitaxsentan