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

NCT ID: NCT01159639

Last Updated: 2013-08-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2013-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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Coronary Artery Disease Aspirin Resistance

Keywords

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aspirin resistance coronary artery bypass grafting multiple electrode aggregometry multiplate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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aspirin low responders monotherapy

patients with inappropriate response to aspirin assessed by multiple electrode aggregometry

Group Type NO_INTERVENTION

No interventions assigned to this group

aspirin low responders dual antiplatelet therapy

patients with inappropriate response to aspirin 300 mg therapy after CABG, randomized to receive clopidogrel 75 mg in addition to aspirin

Group Type ACTIVE_COMPARATOR

Clopidogrel

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Zagreb

OTHER

Sponsor Role lead

Responsible Party

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Medical school, University of Zagreb, University hospital center Zagreb-Rebro

Locations

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Medical school Zagreb, University hospital center Zagreb

Zagreb, Croatia, Croatia

Site Status

Countries

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Croatia

References

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Kopjar T, Petricevic M, Gasparovic H, Svetina L, Milicic D, Biocina B. Postoperative Atrial Fibrillation Is Associated With High On-Aspirin Platelet Reactivity. Ann Thorac Surg. 2015 Nov;100(5):1704-11. doi: 10.1016/j.athoracsur.2015.05.001. Epub 2015 Jul 26.

Reference Type DERIVED
PMID: 26215778 (View on PubMed)

Petricevic M, Kopjar T, Gasparovic H, Milicic D, Svetina L, Zdilar B, Boban M, Mihaljevic MZ, Biocina B. Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639). J Thromb Thrombolysis. 2015 May;39(4):522-31. doi: 10.1007/s11239-014-1127-9.

Reference Type DERIVED
PMID: 25095738 (View on PubMed)

Gasparovic H, Petricevic M, Kopjar T, Djuric Z, Svetina L, Biocina B. Impact of dual antiplatelet therapy on outcomes among aspirin-resistant patients following coronary artery bypass grafting. Am J Cardiol. 2014 May 15;113(10):1660-7. doi: 10.1016/j.amjcard.2014.02.024. Epub 2014 Mar 1.

Reference Type DERIVED
PMID: 24666617 (View on PubMed)

Gasparovic H, Petricevic M, Kopjar T, Djuric Z, Svetina L, Biocina B. Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639]. Trials. 2012 Aug 25;13:148. doi: 10.1186/1745-6215-13-148.

Reference Type DERIVED
PMID: 22920307 (View on PubMed)

Other Identifiers

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8.1-10/41-2

Identifier Type: -

Identifier Source: org_study_id