Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension

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art_SOUZA_Safety_and_efficacy_of_sitaxsentan_50_and_100_2012_eng.pdf (304.7 KB)
Citações na Scopus
33
Tipo de produção
article
Data de publicação
2012
Editora
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
SANDOVAL, Julio
TORBICKI, Adam
RAMIREZ, Alicia
KURZYNA, Marcin
DIAZ, Carlos Jerjes-Sanchez
TEAL, Simon A.
HWANG, Lie-Ju
PULIDO, Tomas
Autor de Grupo de pesquisa
STRIDE-4 Investigators
Editores
Coordenadores
Organizadores
Citação
PULMONARY PHARMACOLOGY & THERAPEUTICS, v.25, n.1, p.33-39, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 Background: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury.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.
Palavras-chave
Sitaxsentan, Pulmonary arterial hypertension, Endothelin, Endothelin receptor antagonist, Functional class
URI
https://observatorio.fm.usp.br/handle/OPI/138
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/09