Multiple Daily Doses of Aspirin to Overcome Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)- Part B
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|ClinicalTrials.gov Identifier: NCT01902498|
Recruitment Status : Completed
First Posted : July 18, 2013
Last Update Posted : March 19, 2015
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 at blocking platelet activity than giving aspirin once daily.
|Condition or disease||Intervention/treatment||Phase|
|Postoperative Dysfunction Following Cardiac Surgery||Drug: Aspirin||Phase 2|
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 162mg BID 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 162mg bid 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Investigator, Outcomes Assessor)|
|Official Title:||Multiple Daily Doses of Aspirin to Overcome Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)- Part B|
|Study Start Date :||July 2013|
|Actual Primary Completion Date :||March 2014|
|Actual Study Completion Date :||July 2014|
Experimental: Aspirin 162mg twice daily
Patients will receive 162mg twice daily during the postoperative period, until day 7 postop or the end of hospitalization.
Aspirin 81mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.
Active Comparator: Aspirin 325mg daily
Patients will receive 325mg daily during the postoperative period, until day 7 postop or the end of hospitalization.
Aspirin 325mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.
Active Comparator: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period, until day 7 postop or the end of hospitalization.
Aspirin 162mg po twice daily x 7days or end of hospitalization. First dose administered on post op day 1.
- Serum Thromboxane Concentration (ng/ml) [ Time Frame: Postoperative Day 4 ]
- 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. [ Time Frame: Postoperative Day 4 ]
- DNA genetic analyses for single nucleotide polymorphisms [ Time Frame: A single preoperative blood sample was drawn (on average 1 day prior to surgery) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01902498
|Hamilton General Hospital|
|Hamilton, Ontario, Canada, L8L2X2|
|Principal Investigator:||Jeremy Paikin, MD||Cardiology Fellow|
|Principal Investigator:||John Eikelboom, MBBS||Hematologist, PHRI researcher|
|Principal Investigator:||Richard Whitlock, MD||Cardiac Surgeon, PHRI researcher|
|Principal Investigator:||Guillaume Pare, MD||Medical Biochemist, PHRI researcher|
|Principal Investigator:||Jack Hirsh, MD||Hematologist, Professor Emeritus, PHRI researcher|