Multiple Daily Doses Of Aspirin To Overcome Aspirin Hyporesponsiveness Post Cardiac Bypass Surgery

NCT ID: NCT01618006

Last Updated: 2015-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2013-08-31

Brief Summary

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.

Detailed Description

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.

Conditions

Postoperative; Dysfunction Following Cardiac Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Aspirin 81mg daily

Patients will receive 81mg daily during the postoperative period.

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

Aspirin 81mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.

Aspirin 325mg daily

Patients will receive 325mg daily during the postoperative period, until day 7 postop or the end of hospitalization.

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

Aspirin 325mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.

Aspirin 81mg four times daily

Patients will receive ASA 81mg four times daily until postoperative day 7 or end of hospitalization

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

Aspirin 81mg po four times daily x 7days or end of hospitalization. First dose administered on post op day 1.

Interventions

Aspirin

Aspirin 81mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.

Intervention Type: DRUG

Aspirin

Aspirin 325mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.

Intervention Type: DRUG

Aspirin

Aspirin 81mg po four times daily x 7days or end of hospitalization. First dose administered on post op day 1.

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: lead

Responsible Party

Jeremy Paikin

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeremy Paikin, MD

Role: PRINCIPAL_INVESTIGATOR

Cardiology Fellow

John Eikelboom, MBBS

Role: PRINCIPAL_INVESTIGATOR

Hematologist, PHRI researcher

Richard Whitlock, MD

Role: PRINCIPAL_INVESTIGATOR

Cardiac Surgeon, PHRI researcher

Guillaume Pare, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Biochemist, PHRI researcher

Jack Hirsh, MD

Role: STUDY_CHAIR

Hematologist, Professor Emeritus, PHRI researcher

Locations

Hamilton General Hospital

Hamilton, Ontario, Canada

Countries

Canada

Other Identifiers

NIF-11271

Identifier Type: -

Identifier Source: org_study_id