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

Acute Coronary Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02096419
• Other study ID #: 108-1081875-1993-1
• Status: Completed
• Phase: Phase 4
• First received: March 19, 2014
• Last updated: August 14, 2014
• Start date: February 2012
• Est. completion date: February 2014

Study information

• Verified date: August 2014
• Source: University of Zagreb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Croatia: Ministry of Science, Education and Sports
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: February 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Syndrome

Intervention

Drug:
• 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)

Locations

Country	Name	City	State
Croatia	University Hospital Centre Zagreb	Zagreb

Sponsors (3)

Lead Sponsor	Collaborator
University of Zagreb	Clinical Hospital Centre Zagreb, Ministry of Science, Education and Sport, Republic of Croatia

Country where clinical trial is conducted

Croatia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	clinical outcome - composite endpoint of total cardiovascular death, non-fatal myocardial infarction, target vessel revascularization and ischemic stroke	Data will be collected during the entire follow up period on interviews and analyzing patient medical data.	12 months	No
Secondary	number of bleeding events	BARC classification (Bleeding Academic Research Consortium); Type 0: no evidence of bleeding; Type 1: bleeding without need for hospitalization or treatment (e.g. bruising, hematoma, nosebleeds, etc.); Type 2: any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3, 4 or 5.; Type 3: clinical, laboratory, and/or imaging evidence of bleeding, with healthcare provider responses; Type 4: Coronary Artery Bypass Graft-related bleeding; Type 5: Fatal bleeding	12 months	Yes