Dual Antiplatelet Therapy in Patients With Aspirin Resistance Following Coronary Artery Bypass Grafting

Coronary Artery Disease Clinical Trial

Official title:

Dual Antiplatelet Therapy in Patients With Aspirin Resistance Following Coronary Artery Bypass Grafting

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01159639
• Other study ID #: 8.1-10/41-2
• Status: Completed
• Phase: Phase 4
• First received: July 8, 2010
• Last updated: August 27, 2013
• Start date: June 2010
• Est. completion date: February 2013

Study information

• Verified date: June 2010
• Source: University of Zagreb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Croatia: Agency for Medicinal Product and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Reactive platelet hyperactivity following coronary artery bypass grafting (CABG) might lead to thrombotic complications and major ischemic cardiac events. The aim of this study is to evaluate the changes in platelet reactivity following CABG and to clarify a potentially beneficial effect of dual antiplatelet therapy in the group of patients with documented aspirin resistance following CABG. Platelet function will be assessed by multiple electrode aggregometry. Aortocoronary vein graft disease is comprised of three distinct but interrelated pathological processes: thrombosis, intimal hyperplasia and atherosclerosis. Early vein thrombosis is a major cause of vein graft attrition during the first month after CABG.

Bypass patency can be improved with antiplatelet therapy which is the mainstay of treatment for patients after CABG. A beneficial effect of acetylsalicylic acid (ASA) on vein graft patency has been previously shown. Some patients experience thrombotic events despite continuous aspirin administration after CABG. The investigators hypothesized that low responsiveness to aspirin might be a precipitating factor for adverse thrombotic events following CABG.

Low responsiveness to ASA, as assessed by platelet function tests, varies widely among patients. The etiology of postoperative platelet hyperactivity remains to be elucidated.

In this study a new point-of-care assay named multiple electrode aggregometry (MEA) using a device called Multiplate analyzer (Dynabyte, Munich, Germany) has been utilized. It allows for rapid and standardized assessment of platelet function parameters.

This is a prospective randomized trial. The aim of the study is to document whether introduction of dual antiplatelet therapy in patients with ASA resistance will lead to a lower incidence of major adverse cardiac events (MACE) at a six month follow up. The composite endpoint will include death, non-fatal myocardial infarction, stroke and cardiac rehospitalization. All patients will receive 300 mg of ASA starting 6 hours after surgery, provided that the chest tube output is minimal. On postoperative day 4 their platelet function will be assessed using the above mentioned MEA. The patients found to be aspirin resistant will then undergo the process of randomization. The first arm will include patients with ASA resistance in whom no additional antiaggregation will be administered. In the second arm the investigators will include patients who were randomized to receive 75 mg of clopidogrel in addition to the standard antiplatelet regimen of 300 mg of ASA.

Platelet function monitoring allows for individual tailoring of the antiplatelet therapy. The goal of this study is to define whether this strategy will lead to improved patient outcomes. Both major and minor bleeding complications will be strictly monitored and reported.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Isolated coronary artery bypass grafting

• Patients older than 18 years

• Written informed consent

• Accurate antiplatelet therapy administration documentation

Exclusion Criteria:

• Missing consent

• Patients with cardiac surgical procedures other than isolated CABG

• Antiplatelet therapy other than aspirin 300 mg after CABG

• Previous PCI requiring clopidogrel therapy after CABG

• Patients with unknown preoperative anti-platelet status

• Urgent or emergent surgery

• Off-pump CABG

• Re-Do CABG

• Patients younger than 18 years

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Aspirin Resistance
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Clopidogrel
patients with inappropriate response to aspirin 300 mg after CABG, assessed by multiple electrode aggregometry are randomized to receive clopidogrel 75 mg daily dose

Locations

Country	Name	City	State
Croatia	Medical school Zagreb, University hospital center Zagreb	Zagreb

Sponsors (1)

Lead Sponsor	Collaborator
University of Zagreb

Country where clinical trial is conducted

Croatia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MACE events	MACE: death; non-fatal myocardial infarction; stroke; cardiac rehospitalization	6 months	Yes