Continuous Clopidogrel Dose Adjustment in Acute Coronary Syndrome Patients With High On-treatment Platelet Reactivity

NCT ID: NCT02096419

Last Updated: 2014-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2014-02-28

Brief Summary

The purpose of this study is to determine whether continuous clopidogrel dose adjustment targeted after platelet function testing improves outcomes during 12 months of follow-up in acute coronary syndrome patients treated with coronary artery stenting and with determined high platelet reactivity on clopidogrel.

Detailed Description

Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 receptor antagonists during 12 months presents cornerstone treatment in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Clopidogrel is the most widely used P2Y12 inhibitor despite it's limitations that include highly variable P2Y12-receptor inhibition which causes wide interindividual platelet reactivity variability. Since high on-treatment platelet reactivity (HTPR) on clopidogrel is strongly associated with adverse events, antiplatelet therapy tailoring has been vastly investigated to determine whether individualized approach could improve outcomes. In the time of progressive personalized approach to therapy, effective strategies are needed to minimize the risk of ischemic adverse events without increasing the risk for bleeding.

Aim of this study is to investigate whether continuous clopidogrel dose adjustment according to platelet function testing (PFT) using Multiplate® function analyzer (Roche Diagnostics, Mannheim, Germany) could decrease the rate of adverse events in ACS patients treated with PCI and with HTPR during early and late period of DAPT treatment.

Cut off values for HTPR and enhanced platelet response were set according to the consensus statement at >46 U and <19 U, respectively. PFT and therapy tailoring was performed at day 1, 2, 3, 7, 30 and month 2, 3, 6, 9 and 12.

Conditions

Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

control group

Patients in this group will receive standard clopidogrel dose

Group Type: NO_INTERVENTION

No interventions assigned to this group

interventional group

Patients in the interventional arm will receive clopidogrel dose adjustment to maintain optimal platelet reactivity determined by Multiplate function analyzer (19-46U).

They will undergo platelet function testing on day 1,2,3,7,30 and month 2,3,6,9 and 12.

On first two measurements patients will receive up to 2 additional clopidogrel loading doses (600 mg) and put on 150 mg and 75 mg a day if platelet reactivity >18U and <18U, respectively. Maintenance dose will be determined on following measurements - increased by 75 mg if >46U; not changed if 19-46U; decreased by 75 mg if <19U. Minimal dose - 75 mg; maximal dose 300 mg (for patients >70 years 150 mg)

Group Type: EXPERIMENTAL

Clopidogrel dose adjustment

Intervention Type: DRUG

Patients in the interventional arm will receive clopidogrel dose adjustment to maintain optimal platelet reactivity determined by Multiplate function analyzer (19-46U).

They will undergo platelet function testing on day 1,2,3,7,30 and month 2,3,6,9 and 12.

On first two measurements patients will receive up to 2 additional clopidogrel loading doses (600 mg) and put on 150 mg and 75 mg a day if platelet reactivity >18U and <18U, respectively. Maintenance dose will be determined on following measurements - increased by 75 mg if >46U; not changed if 19-46U; decreased by 75 mg if <19U. Minimal dose - 75 mg; maximal dose 300 mg (for patients >70 years 150 mg)

Interventions

Clopidogrel dose adjustment

Patients in the interventional arm will receive clopidogrel dose adjustment to maintain optimal platelet reactivity determined by Multiplate function analyzer (19-46U).

They will undergo platelet function testing on day 1,2,3,7,30 and month 2,3,6,9 and 12.

On first two measurements patients will receive up to 2 additional clopidogrel loading doses (600 mg) and put on 150 mg and 75 mg a day if platelet reactivity >18U and <18U, respectively. Maintenance dose will be determined on following measurements - increased by 75 mg if >46U; not changed if 19-46U; decreased by 75 mg if <19U. Minimal dose - 75 mg; maximal dose 300 mg (for patients >70 years 150 mg)

Intervention Type: DRUG

Other Intervention Names

antiplatelet therapy tailoring

Eligibility Criteria

Inclusion Criteria

• acute coronary syndrome patients treated with successful PCI
• age 18-80 years
• determined high on-treatment platelet reactivity

Exclusion Criteria

• continuous postinterventional glycoprotein (GP) IIbIIIa receptor inhibitor infusion
• thrombocytopenia (<150x109/L)
• significant renal insufficiency (creatinine>200 µmol/L)
• anemia (Htc<30%)
• hemorrhagic diathesis
• history of intracranial bleeding or ischemic cerebrovascular insult 6 months before
• major operation 6 weeks before
• concomitant chronic anticoagulation therapy
• age <18 years and >80 years

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Hospital Centre Zagreb

OTHER

Sponsor Role: collaborator

Ministry of Science, Education and Sport, Republic of Croatia

OTHER_GOV

Sponsor Role: collaborator

University of Zagreb

OTHER

Sponsor Role: lead

Responsible Party

Jure Samardzic

Jure Samardzic M.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Davor Milicic, MD, PhD

Role: STUDY_CHAIR

University of Zagreb School of Medicine

Jure Samardzic, MD

Role: PRINCIPAL_INVESTIGATOR

University of Zagreb School of Medicine

Locations

University Hospital Centre Zagreb

Zagreb, , Croatia

Countries

Croatia

Other Identifiers

108-1081875-1993-1

Identifier Type: -

Identifier Source: org_study_id