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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Ontario
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Hamilton、Ontario、カナダ、L8L2X2
- Hamilton General Hospital
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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)
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
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アスピリン 81mg を毎日 7 日間経口投与、または入院終了。
最初の投与は術後 1 日目に投与されました。
アスピリン 325mg を毎日 7 日間経口投与、または入院終了。
最初の投与は術後 1 日目に投与されました。
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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|
アクティブコンパレータ：アスピリン 1日325mg
患者は、術後7日目または入院が終わるまで、術後期間中毎日325mgを投与されます。
|
アスピリン 81mg を毎日 7 日間経口投与、または入院終了。
最初の投与は術後 1 日目に投与されました。
アスピリン 325mg を毎日 7 日間経口投与、または入院終了。
最初の投与は術後 1 日目に投与されました。
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
|
|
実験的：Aspirin 81mg four times daily
Patients will receive ASA 81mg four times daily until postoperative day 7 or end of hospitalization
|
アスピリン 81mg を毎日 7 日間経口投与、または入院終了。
最初の投与は術後 1 日目に投与されました。
アスピリン 325mg を毎日 7 日間経口投与、または入院終了。
最初の投与は術後 1 日目に投与されました。
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
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
時間枠：Postoperative Day 4
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Postoperative Day 4
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
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アラキドン酸誘導光透過凝集測定法 (LTA): 凝集は、参照として使用される乏血小板血漿を使用した、ベースラインからの光透過率の最大変化パーセントとして表されます。
時間枠：術後4日目
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術後4日目
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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).
時間枠：Postoperative Day 4
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Postoperative Day 4
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DNA genetic analyses for single nucleotide polymorphisms
時間枠：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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協力者と研究者
捜査官
- 主任研究者：Jeremy Paikin, MD、Cardiology Fellow
- 主任研究者：John Eikelboom, MBBS、Hematologist, PHRI researcher
- 主任研究者：Richard Whitlock, MD、Cardiac Surgeon, PHRI researcher
- 主任研究者：Guillaume Pare, MD、Medical Biochemist, PHRI researcher
- スタディチェア：Jack Hirsh, MD、Hematologist, Professor Emeritus, PHRI researcher
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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