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

This study has been completed.
Sponsor:
Information provided by:
University of Zagreb
ClinicalTrials.gov Identifier:
NCT01159639
First received: July 8, 2010
Last updated: August 27, 2013
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Aspirin Resistance
Drug: Clopidogrel
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Dual Antiplatelet Therapy in Patients With Aspirin Resistance Following Coronary Artery Bypass Grafting

Resource links provided by NLM:


Further study details as provided by University of Zagreb:

Primary Outcome Measures:
  • MACE events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    MACE: death; non-fatal myocardial infarction; stroke; cardiac rehospitalization


Enrollment: 200
Study Start Date: June 2010
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: aspirin low responders monotherapy
patients with inappropriate response to aspirin assessed by multiple electrode aggregometry
Active Comparator: 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
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01159639

Locations
Croatia
Medical school Zagreb, University hospital center Zagreb
Zagreb, Croatia, 10000
Sponsors and Collaborators
University of Zagreb
  More Information

No publications provided by University of Zagreb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hrvoje Gasparovic,MD.PhD, Medical school, University of Zagreb, University hospital center Zagreb-Rebro
ClinicalTrials.gov Identifier: NCT01159639     History of Changes
Other Study ID Numbers: 8.1-10/41-2
Study First Received: July 8, 2010
Last Updated: August 27, 2013
Health Authority: Croatia: Agency for Medicinal Product and Medical Devices

Keywords provided by University of Zagreb:
aspirin resistance
coronary artery bypass grafting
multiple electrode aggregometry
multiplate

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Aspirin
Clopidogrel
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014