sPLA2 Inhibition to Decrease Enzyme Release After PCI Trial (SPIDER-PCI)
sPLA2 Inhibition to Decrease Enzyme Release After PCI (SPIDER-PCI) Trial
As evidence accumulates that atherogenesis or Coronary Artery Disease (CAD) may not be simply a disorder of lipid metabolism, but an inflammatory disease, the focus of treatment has shifted. A-002 or Varespladib is an anti-inflammatory drug for treatment of chronic and acute diseases. It acts by inhibiting secretory phospholipase A2 (sPLA2 ) - one of a family of enzymes leading to inflammation - which may be important in: 1) the development of atherosclerosis and 2) the increase in occurence of cardiovascular events after angioplasty. Previous studies have demonstrated that sPLA2: 1) facilitates the pro-atherogenic effects of low-density (LDL or bad cholesterol) and 2) increased levels post-angioplasty correlate with an increased risk of events at followup contact. Therefore this study proposes to investigate the ability of A-002 to prevent or reduce myocardial damage after angioplasty by inhibiting the cascade of inflammatory mediators.
Substudy - Subjects who agree will also have a vascular ultrasound 24h post-PCI to assess endothelial function.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Tissue injury after angioplasty is likely due to micro-emboli from mechanical trauma to a thrombotic lesion during angioplasty. In response to the ischemia sPLA2, possibly localized within atherosclerotic vascular tissue as well as from macrophages and monocytes, is released. Following ischemia-induced release, sPLA2 can bind to ischemically challenged cardiomyocytes and adversely affect their survival either directly through toxic effects on cardiomyocytes or indirectly by facilitating inflammation. It may be possible through sPLA2 inhibition to salvage non-lethally jeopardized cells following an ischemic episode thereby reducing the infarcted area and amount of tissue damage. Previous studies in patients with unstable angina support this hypothesis, and conclude that sPLA2 levels can be used to predict clinical outcomes. We hypothesize that sPLA2 inhibition with A-002 will reduce myocardial injury post-angioplasty.
Substudy - Peripheral vascular ultrasound should be done prior to receiving study drug and 24h post-PCI. Coronary endothelial function will be assessed at the time of PCI.
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Ontario
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Toronto, Ontario, Canadá, M5G 2C4
- Toronto General Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Men or women ≥ 18 years of age undergoing elective PCI, with or without stenting
Exclusion Criteria:
- ST elevation MI or any troponin elevation (non-STEMI) within preceding 10days
- Elevation of CK-MB or troponin I at baseline
- Recent (4 weeks) coronary bypass surgery
- NYHA class III-IV heart failure
- Left ventricular ejection fraction < 0.30
- Severe valvular heart disease
- Chronic inflammatory disease (e.g., lupus, rheumatoid arthritis, inflammatory bowel disease), or patients receiving steroid drugs
- Presence of severe liver disease with cirrhosis
- Recent active hepatitis
- Active chronic hepatitis
- ALT or AST > 3 × upper limit of normal (ULN)
- Biliary obstruction with hyperbilirubinemia (total bilirubin > 2 × ULN)
- Moderate or severe renal impairment (creatinine > 1.5 × ULN)
- Nephrotic syndrome or subjects undergoing dialysis
- Uncontrolled diabetes (HbA1c > 11% 1 month prior to screening)
- Initiation of statin therapy within 30 days
- Inability to provide consent.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador de placebos: Control
Subjects take 2 tablets BID.
Placebo tablets are identical to active medication.
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250mg tablets BID 3-5 days pre-angioplasty and 5 days post-angioplasty.
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Experimental: Varespladib (A-002)
Subjects take 250mg tablets BID beginning 3-5 days pre-angioplasty and for 5 days post-angioplasty.
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250mg tablets BID for 3-5 days pre-angioplasty and 5 days post-angioplasty.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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The primary endpoint will be incidence of myocardial injury as evidenced by elevation of CK-MB or troponin I above the upper limit of normal.
Periodo de tiempo: 8 hours and 18-24 hours post-angioplasty
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8 hours and 18-24 hours post-angioplasty
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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A secondary endpoint will be occurrence of elevation of CK-MB or troponin I above the upper limit of normal.
Periodo de tiempo: 8 and 18-24 hours post-angioplasty
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8 and 18-24 hours post-angioplasty
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A secondary endpoint will be occurrence of any major adverse cardiac events (MACE).
Periodo de tiempo: 30 days post-angioplasty
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30 days post-angioplasty
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A secondary outcome will be serum sPLA2 activity.
Periodo de tiempo: 5-7 days post-angioplasty
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5-7 days post-angioplasty
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Isquemia miocardica
- Enfermedades cardíacas
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Arteriosclerosis
- Enfermedades arteriales oclusivas
- Enfermedad coronaria
- Enfermedad de la arteria coronaria
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Inhibidores de la fosfolipasa A2
- Varespladib metilo
Otros números de identificación del estudio
- SPIDER001
- A Sub-study of SPIDER-PCI
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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