Clinical trial NCT02096419: Continuous Clopidogrel Dose Adjustment in Acute Coronary Syndrome Patients With High On-treatment Platelet Reactivity
Official title: Effect of Continuous Clopidogrel Dosing Targeted After Platelet Function Testing in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention With High On-treatment Platelet Reactivity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: clopidogrel
platelet reactivity
acute coronary syndrome
tailoring therapy
outcome
Lead sponsor: University of Zagreb
Sponsor class: OTHER
Collaborators: name: Clinical Hospital Centre Zagreb
name: Ministry of Science, Education and Sport, Republic of Croatia
First posted: 2014-03-26
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: clinical outcome - composite endpoint of total cardiovascular death, non-fatal myocardial infarction, target vessel revascularization and ischemic stroke
timeFrame: 12 months
Secondary outcomes:
measure: number of bleeding events
timeFrame: 12 months
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
Study officials:
affiliation: University of Zagreb School of Medicine
name: Davor Milicic, MD, PhD
role: STUDY_CHAIR
affiliation: University of Zagreb School of Medicine
name: Jure Samardzic, MD
role: PRINCIPAL_INVESTIGATOR
References: