Multiple Daily Doses Of Aspirin To Overcome Aspirin Hyporesponsiveness Post Cardiac Bypass Surgery
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects who undergo elective or urgent CABG surgery who are on or off aspirin during the preoperative period
排除标准
- •(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)
研究组 & 干预措施
Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
干预措施: Aspirin (Drug)
Aspirin 325mg daily
Patients will receive 325mg daily during the postoperative period, until day 7 postop or the end of hospitalization.
干预措施: Aspirin (Drug)
Aspirin 81mg four times daily
Patients will receive ASA 81mg four times daily until postoperative day 7 or end of hospitalization
干预措施: Aspirin (Drug)
结局指标
主要结局
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
时间窗: Postoperative Day 4
次要结局
- Arachidonic Acid Induced Light Transmission Aggregometry (LTA): Aggregation will be expressed as the maximum percent change in light transmittance from baseline, with platelet-poor plasma used as a reference.(Postoperative Day 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).(Postoperative Day 4)
- DNA genetic analyses for single nucleotide polymorphisms(A single preoperative blood sample was drawn (on average of 1 week prior to surgery))
研究者
Jeremy Paikin
Principal Investigator
Hamilton Health Sciences Corporation