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

This study has been completed.
Sponsor:
Collaborators:
Clinical Hospital Centre Zagreb
Ministry of Science, Education and Sport, Republic of Croatia
Information provided by (Responsible Party):
Jure Samardzic, University of Zagreb
ClinicalTrials.gov Identifier:
NCT02096419
First received: March 19, 2014
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Acute Coronary Syndrome
Drug: Clopidogrel dose adjustment
Phase 4

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

Resource links provided by NLM:


Further study details as provided by University of Zagreb:

Primary Outcome Measures:
  • clinical outcome - composite endpoint of total cardiovascular death, non-fatal myocardial infarction, target vessel revascularization and ischemic stroke [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Data will be collected during the entire follow up period on interviews and analyzing patient medical data.


Secondary Outcome Measures:
  • number of bleeding events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

    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


Enrollment: 87
Study Start Date: February 2012
Study Completion Date: February 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: control group
Patients in this group will receive standard clopidogrel dose
Experimental: 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)

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)

Other Name: antiplatelet therapy tailoring

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT02096419

Locations
Croatia
University Hospital Centre Zagreb
Zagreb, Croatia, 10000
Sponsors and Collaborators
University of Zagreb
Clinical Hospital Centre Zagreb
Ministry of Science, Education and Sport, Republic of Croatia
Investigators
Study Chair: Davor Milicic, MD, PhD University of Zagreb School of Medicine
Principal Investigator: Jure Samardzic, MD University of Zagreb School of Medicine
  More Information

No publications provided

Responsible Party: Jure Samardzic, Jure Samardzic M.D., University of Zagreb
ClinicalTrials.gov Identifier: NCT02096419     History of Changes
Other Study ID Numbers: 108-1081875-1993-1
Study First Received: March 19, 2014
Last Updated: August 14, 2014
Health Authority: Croatia: Ministry of Science, Education and Sports

Keywords provided by University of Zagreb:
clopidogrel
platelet reactivity
acute coronary syndrome
tailoring therapy
outcome

Additional relevant MeSH terms:
Acute Coronary Syndrome
Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Disease
Pathologic Processes
Clopidogrel
Ticlopidine
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on October 19, 2014