Effects of Intensive Antiplatelet Therapy for Patients With Clopidogrel Resistance After Coronary Stent Implantation

Clopidogrel resistance (CR) or low-responsiveness is associated with increased risk of ischemic events and can be detected by laboratory tests. This multicenter, randomized study is aimed to explore the efficacy and safety of intensive antiplatelet therapy (i.e. double clopidogrel maintenance dose and/or additional cilostazol)for patients with CR after coronary stenting.

Study Overview

• Status: Completed
• Conditions: Percutaneous Coronary Intervention; Acute Coronary Syndromes; Clopidogrel Low Responsiveness
• Intervention / Treatment: Drug: aspirin, clopidogrel; Drug: aspirin, clopidogrel, cilostazol

• Study Type: Interventional
• Enrollment (Actual): 840
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • 463 Hospital of PLA
    • Shenyang, Liaoning, China, 110016
      • Shengjing Hospital of China Medical University
    • Shenyang, Liaoning, China, 110840
      • Shenyang Northern Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criterial:

• aged 35 to 75 years
• acute coronary syndromes
• underwent successful coronary stent implantation
• informed consent

Exclusion Criteria:

• contraindications to antiplatelet therapy
• history of intracranial bleeding
• known bleeding disorders
• severe liver or kidney disease
• pregnancy
• left main coronary artery disease
• planned non cardiac surgery within 1 year
• end stage of other serious disease with life expectancy less than 1 year
• heart failure with NYHA grade 3 to 4

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: standard group; patients in this group received standard dual antiplatelet therapy, i.e. aspirin 300mg/d and clopidogrel 75mg/d	Drug: aspirin, clopidogrel; patients in the standard group received standard dual antiplatelet therapy: aspirin 300mg/d for 30 days followed by 100mg/d indefinitely, clopidogrel 75mg/d for at least 1 year
Experimental: intensive group; patients in this group received intensive antiplatelet therapy and the regimen can be adjusted according to results of platelet aggregation function test by LTA	Drug: aspirin, clopidogrel, cilostazol; Firstly,all patients in this group were received aspirin 300mg/d and clopidogrel 150mg/d for 3 days. Then a platelet aggregation function test was performed. The regimen will lasted for another 27 days if patients were judged as responsive to current clopidogrel dose. Patients still with clopidogrel resistance were then randomly assigned to receive clopidogrel 75mg/d plus cilostazol 100mg, twice per day or clopidogrel 150mg/d plus cilostazol 50mg, twice per day for 27 days. At 30-day, a repeat platelet aggregation function test wil performed for all patients. Then a standard dual antiplatelet regimen with aspirin 100mg/d indefinitely and clopidogrel 75mg/d for at least 1 year will be prescribed for all patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major ischemic cardiovascular events	defined as a composite of cardiac death, myocardial infarction or stroke	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stent thrombosis	according to ARC definition	1 year
major adverse cardiac and cerebral events(MACCE)	defined as a composite of cardiac death, myocardial infarction, target vessel revascularization or stroke	1 year
Hemorrhagic events	according to TIMI bleeding definition	within 1 year
reduction in ADP induced platelet aggregation	assessed by LTA (Packs-4 Aggregometer, Helena labs, Beaumont, Texas)	30 days

Collaborators and Investigators

• Sponsor: Shenyang Northern Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: March 26, 2010
• First Submitted That Met QC Criteria: March 26, 2010
• First Posted (Estimate): March 29, 2010

Study Record Updates

• Last Update Posted (Estimate): June 14, 2012
• Last Update Submitted That Met QC Criteria: June 13, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; cilostazol; antiplatelet therapy; acute coronary syndromes; clopidogrel low responsiveness
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Aspirin; Clopidogrel; Cilostazol
• Other Study ID Numbers: 825004-5