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.
研究概览
详细说明
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.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Ontario
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Hamilton、Ontario、加拿大、L8L2X2
- Hamilton General Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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)
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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有源比较器：Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
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阿司匹林 81mg po 每日 x 7 天或住院结束。
第一剂在术后第 1 天给药。
阿司匹林 325mg po 每日 x 7 天或住院结束。
第一剂在术后第 1 天给药。
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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有源比较器：阿司匹林 325mg 每日
患者将在术后期间每天接受 325mg，直至术后第 7 天或住院结束。
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阿司匹林 81mg po 每日 x 7 天或住院结束。
第一剂在术后第 1 天给药。
阿司匹林 325mg po 每日 x 7 天或住院结束。
第一剂在术后第 1 天给药。
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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实验性的：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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阿司匹林 81mg po 每日 x 7 天或住院结束。
第一剂在术后第 1 天给药。
阿司匹林 325mg po 每日 x 7 天或住院结束。
第一剂在术后第 1 天给药。
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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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
大体时间：Postoperative Day 4
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Postoperative Day 4
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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花生四烯酸诱导的光透射聚集测定法 (LTA)：聚集将表示为相对于基线的光透射率的最大百分比变化，贫血小板血浆用作参考。
大体时间：术后第 4 天
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术后第 4 天
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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).
大体时间：Postoperative Day 4
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Postoperative Day 4
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DNA genetic analyses for single nucleotide polymorphisms
大体时间：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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合作者和调查者
调查人员
- 首席研究员：Jeremy Paikin, MD、Cardiology Fellow
- 首席研究员：John Eikelboom, MBBS、Hematologist, PHRI researcher
- 首席研究员：Richard Whitlock, MD、Cardiac Surgeon, PHRI researcher
- 首席研究员：Guillaume Pare, MD、Medical Biochemist, PHRI researcher
- 学习椅：Jack Hirsh, MD、Hematologist, Professor Emeritus, PHRI researcher
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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