Platelet Function Monitoring in Patients Treated With Clopidogrel at the Time of Primary Percutaneous Coronary Angioplasty

This study has been completed.
Sponsor:
Information provided by:
University of Ottawa Heart Institute
ClinicalTrials.gov Identifier:
NCT00827346
First received: January 20, 2009
Last updated: April 28, 2011
Last verified: April 2011
  Purpose

Platelets are a major component of clot formation which can lead to clotting events such as heart attack. During treatment for a heart attack, doctors try to remove this blockage as quickly as possible so that the heart can recover and start to work properly again. The standard of care at the Heart Institute for patients having a heart attack is a procedure called a Percutaneous Coronary Angioplasty. A drug called Clopidogrel (Plavix) is routinely used prior to the angioplasty to prevent blood clots. Patients usually remain on Clopidogrel for at least one year following the angioplasty. Clopidogrel works by preventing the blood from forming sticky substances called platelets, which clump together to form clots. Despite the routine use of Clopidogrel, some patients still return to the hospital with another heart attack, or with more chest pain. There is a growing body of evidence that recurrence of these complications may be attributed to some patients having a poor response to Clopidogrel.

This pilot study will examine how platelets react to different doses of Clopidogrel given to patients having a heart attack.


Condition Intervention Phase
Platelet Reactivity
Drug: Clopidogrel
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Platelet Function Monitoring in Patients Treated With Clopidogrel at the Time of Primary Percutaneous Coronary Angioplasty

Resource links provided by NLM:


Further study details as provided by University of Ottawa Heart Institute:

Primary Outcome Measures:
  • The primary objective of this randomized pilot study is to evaluate the inhibition of platelet aggregation (IPA) amongst 4 different loading doses of clopidogrel in patients with STEMI treated with bivalirudin as anticoagulant for PCI [ Time Frame: Up to 48hrs ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical events (death reinfarction, stroke, bleeding) [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
  • The percent TIMI grade 3 coronary flow at first contrast injection on the base-line angiogram, to TIMI flow after the PCI, [ Time Frame: Pre and post ballon injection ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: January 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1
600-mg double dose
Drug: Clopidogrel
600 mg now
Active Comparator: Group 2
600/600-mg double loading dose (first dose 600 mg given immediately upon arrival at the hospital and the second dose 600 mg, 3 hours after the first loading dose for a total of 900 mg
Drug: Clopidogrel
600 mg now and 600 mg in 3 hours
Active Comparator: Group 3
Clopidogrel 900mg
Drug: Clopidogrel
900 mg now
Active Comparator: Group 4
First dose 600 mg given immediately upon arrival at the hospital and the second dose 300 mg, 3 hours after the first loading dose for a total of 900 mg
Drug: Clopidogrel
600 mg now and 300 mg in 3 hours

Detailed Description:

Platelets are a major component of clot formation which can lead to thrombotic events. Antiplatelet agents have been found to reduce cardiovascular events in different clinical settings. The commonest agent that has been used is aspirin which works by inhibiting the cyclooxygenase pathway within the platelet and consequently preventing the release of tromboxane A2. A second group of agents called thienopyridines can inhibit platelets by blocking the P2Y12 receptor. Clopidogrel (Plavix) is currently a widely used thienopyridine that has been used for the treatment of patients presenting with the acute coronary syndrome and patients undergoing percutaneous coronary angioplasty (PCI). Antiplatelet therapy has reduced the occurrence of thrombotic events following PCI, including myocardial infarction and stent thrombosis. However, despite dual therapy with aspirin and clopidogrel, a significant number of patients continue to experience cardiovascular events. There is a now growing body of evidence that recurrence of ischemic complications may be attributed to poor response to clopidogrel and that persistence of enhanced platelet reactivity despite the use of clopidogrel is believed to be clinically relevant.1 The mechanisms leading to poor clopidogrel effects are not fully explained.

Our pilot study will use the VerifyNow device as an ex vivo method to measure platelet inhibition in patients treated with clopidogrel in the setting of STEMI. Since July 2004, the standard of care at the University of Ottawa Heart Institute for the treatment of STEMI has been primary PCI in which all patients receive aspirin 160 mg po either in the field or on arrival in the emergency department and clopidogrel 600 mg po given on arrival to the hospital. Little is known of the pharmacokinetics of clopidogrel in the setting of STEMI. Clopidogrel must be absorbed and activated by the liver to be effective. The physiological mechanisms for these steps may be greatly disturbed in patients presenting with STEMI. Therefore, the purpose of this study will be to examine the degree of platelet inhibition at various time points in this select patient population using the current 600 mg dose of clopidogrel and comparing this dose to other doses of clopidogrel to determine the optimal loading dose in the context of STEMI.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ischemic chest discomfort of greater than 30 minutes duration
  2. Onset of chest pain less than 12 hrs prior to entry into the study
  3. ST segment elevation of > 1 mm (0.1 mV) in two or more contiguous electrocardiographic leads (on a standard 12 lead ECG) or left bundle branch block not known to be old

Exclusion Criteria:

  1. Active bleeding
  2. GI or GU bleed within 2 weeks, or any major bleeding episode within 2 weeks
  3. Stroke within 90 days or intracranial bleeding at any time
  4. Major surgery or trauma within the past six weeks
  5. Uncontrolled hypertension (SBP > 200 mm Hg and/or DBP > 110 mm Hg despite treatment)
  6. Prolonged (>10 min) cardiopulmonary resuscitation
  7. Inadequate vascular access
  8. PCI within the last 30 days
  9. Thrombolytic agents within the preceding 7 days
  10. GP IIb/IIIa antagonists within the preceding 7 days
  11. Coagulation disorder (i.e. INR >2.0, platelets <100,000 / mm3, or hematocrit <30%)
  12. Current warfarin treatment
  13. A subcutaneous therapeutic dose of any LMWH within 12 hours
  14. Intolerance to aspirin or clopidogrel
  15. Patient already on chronic clopidogrel therapy
  16. Other medical condition that is likely to result in death within 12 months
  17. Participation in a study with another investigational device or drug < four weeks
  18. Pregnancy
  19. Known severe renal impairment (creatinine clearance rate of less than 30 ml per minute)
  20. Sustained hypotension defined as SBP < 80 mmHg or the need for IV inotropes and/or intraaortic balloon counterpulsation to support the blood pressure
  21. Known severe contrast (dye) allergy
  22. Inability to provide informed consent
  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: NCT00827346

Locations
Canada, Ontario
University of Ottawa Heart Institute
Ottawa, Ontario, Canada, K1Y 4W7
Sponsors and Collaborators
University of Ottawa Heart Institute
Investigators
Principal Investigator: Michel R Le May, MD FRCPC FACC University of Ottawa Heart Institute
  More Information

No publications provided

Responsible Party: Michel Le May, UOHI
ClinicalTrials.gov Identifier: NCT00827346     History of Changes
Other Study ID Numbers: MRL-A2, 2008239-01H
Study First Received: January 20, 2009
Last Updated: April 28, 2011
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
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 August 28, 2014