Platelet Function Monitoring in Patients Treated With Clopidogrel at the Time of Primary Percutaneous Coronary Angioplasty
Information source: Ottawa Heart Institute Research Corporation
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Platelet Reactivity
Intervention: Clopidogrel (Drug); Clopidogrel (Drug); Clopidogrel (Drug); Clopidogrel (Drug)
Phase: Phase 2/Phase 3
Status: Completed
Sponsored by: Ottawa Heart Institute Research Corporation Official(s) and/or principal investigator(s): Michel R Le May, MD FRCPC FACC, Principal Investigator, Affiliation: Ottawa Heart Institute Research Corporation
Summary
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.
Clinical Details
Official title: Platelet Function Monitoring in Patients Treated With Clopidogrel at the Time of Primary Percutaneous Coronary Angioplasty
Study design: Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Primary outcome: 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
Secondary outcome: Clinical events (death reinfarction, stroke, bleeding)The percent TIMI grade 3 coronary flow at first contrast injection on the base-line angiogram, to TIMI flow after the PCI,
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
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada
Additional Information
Starting date: January 2009
Last updated: April 28, 2011
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