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.
연구 개요
상세 설명
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.
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Ontario
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Hamilton, Ontario, 캐나다, L8L2X2
- Hamilton General Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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)
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 더블
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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활성 비교기: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
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매일 아스피린 81mg 포 x 7일 또는 입원 종료.
수술 후 1일째에 투여된 첫 번째 용량.
매일 아스피린 325mg 포 x 7일 또는 입원 종료.
수술 후 1일째에 투여된 첫 번째 용량.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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활성 비교기: 매일 아스피린 325mg
환자는 수술 후 7일째 또는 입원이 끝날 때까지 매일 325mg을 투여받습니다.
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매일 아스피린 81mg 포 x 7일 또는 입원 종료.
수술 후 1일째에 투여된 첫 번째 용량.
매일 아스피린 325mg 포 x 7일 또는 입원 종료.
수술 후 1일째에 투여된 첫 번째 용량.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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실험적: 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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매일 아스피린 81mg 포 x 7일 또는 입원 종료.
수술 후 1일째에 투여된 첫 번째 용량.
매일 아스피린 325mg 포 x 7일 또는 입원 종료.
수술 후 1일째에 투여된 첫 번째 용량.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
|---|---|
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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
기간: Postoperative Day 4
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Postoperative Day 4
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2차 결과 측정
결과 측정 |
기간 |
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아라키돈산 유도 광투과 응집계(LTA): 응집은 혈소판 부족 혈장을 기준으로 사용하여 기준선으로부터 광투과율의 최대 변화 백분율로 표현됩니다.
기간: 수술 후 4일차
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수술 후 4일차
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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).
기간: Postoperative Day 4
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Postoperative Day 4
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DNA genetic analyses for single nucleotide polymorphisms
기간: 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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공동 작업자 및 조사자
수사관
- 수석 연구원: Jeremy Paikin, MD, Cardiology Fellow
- 수석 연구원: John Eikelboom, MBBS, Hematologist, PHRI researcher
- 수석 연구원: Richard Whitlock, MD, Cardiac Surgeon, PHRI researcher
- 수석 연구원: Guillaume Pare, MD, Medical Biochemist, PHRI researcher
- 연구 의자: Jack Hirsh, MD, Hematologist, Professor Emeritus, PHRI researcher
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- NIF-11271
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아스피린에 대한 임상 시험
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Montreal Heart InstituteInstitut de Recherches Cliniques de Montreal모병제2형 당뇨병 | 제2형 당뇨병 | 혈소판 응집 | 아스피린 | 혈소판 응집 억제제캐나다