52727
document
Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension . 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 BACKGROUND Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury .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 .
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Intervention_Pharmacological
sitaxsentan
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Outcome_Mental
6MWD
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Outcome_Adverse-effects
Adverse events
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Outcome_Adverse-effects
headache , peripheral edema , dizziness , nausea , extremity pain , and
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Participant_Condition
with pulmonary arterial hypertension
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Participant_Condition
with pulmonary arterial hypertension ( PAH )
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Participant_Sample-size
98
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Participant_Sample-size
61 %
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Participant_Condition
baseline
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Participant_Condition
not 6MWD in PAH patients who were mostly WHO functional class II at