Multiple Daily Doses Of Aspirin To Overcome Aspirin Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)
Cardiac bypass surgery is an important treatment for patients with severely blocked arteries (tubes that delivery oxygen and nutrients to the heart). Hundreds of thousands of these operations are done each year to help relieve patients' chest pain and to prevent future heart attacks. The surgery is done by "bypassing" blood flow around badly clogged arteries by sewing on healthy vessels from another part of the body (usually from the leg or the chest). Aspirin (a blood thinner) is given to patients once a day after their surgery because it stops "sticky" cells in the blood (platelets) from blocking these new vessels (which may lead to a future heart attack).
Research has shown that aspirin does not work as well in people after they have bypass surgery as the investigators might expect (for reasons that are not fully understood). One reason aspirin may not work as well after surgery is because the body makes many more platelets after surgery than it would under normal circumstances. All of these new platelets overwhelm the aspirin and continue to be "sticky" and ready to block off arteries. The investigators believe that giving multiple daily doses of aspirin following bypass surgery is more effective than giving aspirin once daily at blocking platelet activity.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
Background:
Cardiovascular disease caused by athero-thrombosis is the number one cause of long-term morbidity and death worldwide. Many patients with advanced coronary disease benefit from Coronary Artery Bypass Graft (CABG) by improving symptoms and increasing their longevity.
However, the benefits of CABG surgery are attenuated by early graft failure. The administration of aspirin in the post-operative period has been shown in randomized controlled trials (RCT) to reduce the risk of graft occlusion, although rates remain unacceptably high. Patients undergoing CABG surgery transiently develop aspirin resistance, which likely contributes to vein graft failure.
The investigators believe the aspirin resistance is a consequence of rapid platelet turnover in the early postoperative period, resulting in a large number of platelets unexposed to aspirin (due to its short half life). The investigators hypothesize that by increasing the frequency of aspirin dosing, the investigators can reverse the aspirin resistance encountered post CABG surgery. The investigators are proposing a RCT comparing two different doses of aspirin (81mg and 325mg daily) to 81mg qid to determine whether multiple daily dosing can overcome aspirin resistance.
(1)Given that platelet production is increased many-fold after CABG surgery (and the short half-life of aspirin), the investigators hypothesize that increasing the frequency of aspirin dosing will lead to the acetylation of a greater number of platelets over the course of the day leading to an improved antiplatelet effect (as measured by serum thromboxane and platelet aggregation assays); (2) The investigators will examine three platelet-related single nucleotide polymorphisms (SNP) that have been implicated in aspirin hyporesponsiveness.
The investigators are proposing a single centre, randomized, open-label, RCT in 60 patients undergoing elective or urgent CABG surgery, to receive ASA 81mg daily, 325mg daily or 81 mg qid starting day 1 post-operatively. All patients will receive 325mg 6hrs following the procedure (day of operation) as long as there is no contraindication for antiplatelet therapy (ie significant bleeding) - as per the investigators centre's standard clinical practice. Further details on aspirin administration and outcome measurements are reported below.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Ontario
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Hamilton, Ontario, Canadá, L8L2X2
- Hamilton 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:
- Adult subjects who undergo elective or urgent CABG surgery who are on or off aspirin during the preoperative period
Exclusion Criteria:
- (a) initial platelet count <100,000 (b) significant liver disease (c) renal impairment (CrCl<30 ml/min/1.73 m2) (d) receiving (or planned) clopidogrel therapy (e) receiving NSAIDs or other drugs that might interfere with aspirin's platelet-inhibitory effect (f) need for therapeutic doses of parenteral or oral anticoagulants after surgery and (g) off-pump CABG (h) clinically important bleeding (chest tube drainage >200ml/hr for 6hrs)
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador activo: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
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Aspirina 81 mg po diarios x 7 días o fin de hospitalización.
Primera dosis administrada el día postoperatorio 1.
Aspirina 325 mg po diarios x 7 días o al final de la hospitalización.
Primera dosis administrada el día postoperatorio 1.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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Comparador activo: Aspirina 325 mg diarios
Los pacientes recibirán 325mg diarios durante el postoperatorio, hasta el día 7 postoperatorio o al final de la hospitalización.
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Aspirina 81 mg po diarios x 7 días o fin de hospitalización.
Primera dosis administrada el día postoperatorio 1.
Aspirina 325 mg po diarios x 7 días o al final de la hospitalización.
Primera dosis administrada el día postoperatorio 1.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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Experimental: Aspirin 81mg four times daily
Patients will receive ASA 81mg four times daily until postoperative day 7 or end of hospitalization
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Aspirina 81 mg po diarios x 7 días o fin de hospitalización.
Primera dosis administrada el día postoperatorio 1.
Aspirina 325 mg po diarios x 7 días o al final de la hospitalización.
Primera dosis administrada el día postoperatorio 1.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
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Serum Thromboxane: Define an inadequate aspirin response as a value >0.69 ng/ml, which is 2 SD above the mean of aspirin-treated patients
Periodo de tiempo: Postoperative Day 4
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Postoperative Day 4
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Agregometría de transmisión de luz inducida por ácido araquidónico (LTA): la agregación se expresará como el cambio porcentual máximo en la transmisión de luz desde el valor inicial, con plasma pobre en plaquetas utilizado como referencia.
Periodo de tiempo: Postoperatorio Día 4
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Postoperatorio Día 4
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Arachidonic Acid Induced Multiple Electrode Platelet Aggregometry (MEA):Aggregation was recorded for 6 minutes and will be reported as the area under the curve (aggregation units x min).
Periodo de tiempo: Postoperative Day 4
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Postoperative Day 4
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DNA genetic analyses for single nucleotide polymorphisms
Periodo de tiempo: A single preoperative blood sample was drawn (on average of 1 week prior to surgery)
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A single preoperative blood sample was drawn (on average of 1 week prior to surgery)
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Jeremy Paikin, MD, Cardiology Fellow
- Investigador principal: John Eikelboom, MBBS, Hematologist, PHRI researcher
- Investigador principal: Richard Whitlock, MD, Cardiac Surgeon, PHRI researcher
- Investigador principal: Guillaume Pare, MD, Medical Biochemist, PHRI researcher
- Silla de estudio: Jack Hirsh, MD, Hematologist, Professor Emeritus, PHRI researcher
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
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes del sistema nervioso periférico
- Inhibidores de enzimas
- Analgésicos
- Agentes del sistema sensorial
- Agentes antiinflamatorios no esteroideos
- Analgésicos no narcóticos
- Agentes antiinflamatorios
- Agentes antirreumáticos
- Agentes fibrinolíticos
- Agentes moduladores de fibrina
- Inhibidores de la agregación plaquetaria
- Inhibidores de la ciclooxigenasa
- Antipiréticos
- Aspirina
Otros números de identificación del estudio
- NIF-11271
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