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.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
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 estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
-
-
Ontario
-
Hamilton, Ontario, Canadá, L8L2X2
- Hamilton General Hospital
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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)
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Comparador Ativo: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
|
Aspirina 81mg VO diariamente x 7 dias ou fim da internação.
Primeira dose administrada no 1º dia pós-operatório.
Aspirina 325mg VO diariamente x 7 dias ou fim da internação.
Primeira dose administrada no 1º dia pós-operatório.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
|
|
Comparador Ativo: Aspirina 325mg ao dia
Os pacientes receberão 325mg diariamente durante o pós-operatório, até o 7º dia de pós-operatório ou o término da internação.
|
Aspirina 81mg VO diariamente x 7 dias ou fim da internação.
Primeira dose administrada no 1º dia pós-operatório.
Aspirina 325mg VO diariamente x 7 dias ou fim da internação.
Primeira dose administrada no 1º dia pós-operatório.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
|
|
Experimental: Aspirin 81mg four times daily
Patients will receive ASA 81mg four times daily until postoperative day 7 or end of hospitalization
|
Aspirina 81mg VO diariamente x 7 dias ou fim da internação.
Primeira dose administrada no 1º dia pós-operatório.
Aspirina 325mg VO diariamente x 7 dias ou fim da internação.
Primeira dose administrada no 1º dia pós-operatório.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
|
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
Prazo: Postoperative Day 4
|
Postoperative Day 4
|
Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
|
Agregometria de Transmissão de Luz Induzida por Ácido Araquidônico (LTA): A agregação será expressa como a variação percentual máxima na transmitância de luz desde a linha de base, com plasma pobre em plaquetas usado como referência.
Prazo: Dia pós-operatório 4
|
Dia pós-operatório 4
|
|
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).
Prazo: Postoperative Day 4
|
Postoperative Day 4
|
|
DNA genetic analyses for single nucleotide polymorphisms
Prazo: A single preoperative blood sample was drawn (on average of 1 week prior to surgery)
|
A single preoperative blood sample was drawn (on average of 1 week prior to surgery)
|
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
- Cadeira de estudo: Jack Hirsh, MD, Hematologist, Professor Emeritus, PHRI researcher
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Agentes do Sistema Nervoso Periférico
- Inibidores Enzimáticos
- Analgésicos
- Agentes do Sistema Sensorial
- Agentes anti-inflamatórios não esteróides
- Analgésicos, Não Narcóticos
- Antiinflamatórios
- Agentes Antirreumáticos
- Agentes Fibrinolíticos
- Agentes Moduladores de Fibrina
- Inibidores da agregação plaquetária
- Inibidores da Ciclooxigenase
- Antipiréticos
- Aspirina
Outros números de identificação do estudo
- NIF-11271
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .