Blood Platelets, Clopidogrel
Conditions
Keywords
blood platelets, platelet aggregation inhibitors, antiplatelet drugs, clopidogrel
Brief summary
Clopidogrel is a medication that is used to decrease the ability of platelets to form blood clots. The theory has been proposed that, in patients with coronary artery disease or stroke, increased platelet function after discontinuation of clopidogrel therapy is associated with an increased clotting risk. However, this theory has never been rigorously tested. The goal of this research is to determine whether discontinuation of clopidogrel results in increased platelet function.
Detailed description
In this study, we will address the question: does discontinuation of clopidogrel result in platelet hyperreactivity? We will perform a double-blind, placebo-controlled, crossover study in normal subjects, in whom platelet reactivity will be measured before clopidogrel or placebo, during clopidogrel or placebo, and at various time points after discontinuation of clopidogrel or placebo. The dose of clopidogrel will be the standard, FDA-approved dose: 75 mg daily. All subjects will be treated with aspirin 81 mg daily throughout the 57 days of study assessment in both the clopidogrel arm and the placebo arm, because the clinically relevant question is: in patients who remain on aspirin, does discontinuation of clopidogrel result in platelet hyperreactivity?
Interventions
Clopidogrel 75mg plus aspirin 81mg, tablet by mouth daily for 14 days.
DRUGplacebo
Placebo plus aspirin 81 mg, tablet by mouth daily for 14 days.
DRUGAspirin
Aspirin 81mg tablet by mouth continued daily alone for 43 days after day 14.
Sponsors
Sanofi
Bristol-Myers Squibb
University of Massachusetts, Worcester
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be a normal healthy subject * Must be between 21-70 years old * Must be able to take aspirin and clopidogrel. * Must be able to have blood drawn 16 times over approximately 3 months.
Exclusion criteria
* Subject who is currently taking aspirin or another anti-platelet drug such as clopidogrel. Subject must be free of these medications for 10 days before enrolling in this study. * Subject who is currently taking a non-steroidal anti-inflammatory drug such as ibuprofen or naproxen. Subject must be free of these medications for 3 days before enrolling in this study. * Subject who is currently taking medications for depression or medications that lower blood pressure or lower blood sugar. * Subject who are pregnant or may become pregnant during the study or who is breast feeding. * Subject with a known allergy to aspirin or clopidogrel. * Cigarette smoking or use of other nicotine product. * Subject with a history of any of the following: coronary artery disease; stroke; bleeding disorder; ongoing bleeding; previous life-threatening hemorrhage; stomach ulcers; gastrointestinal bleeding within the past 1 month; major surgery within the past 1 month; minor surgery within the past 2 weeks; or platelet transfusion within the past 7 days. * Subject with a blood count, measured on the pre-study drug blood sample, that is not in the normal range. * Subject who is enrolled in another clinical trial of an investigational drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Platelet Surface Activated GPIIb-IIIa Complex at 45 Days After Intervention. | Baseline and 45 days after intervention | Value at 45 days after intervention minus value at baseline in platelet surface activated GPIIb-IIIa complex using flow cytometry.The types and concentrations of agonists used in the flow cytometry assays reported here were: ADP 0.5, 1, and 20 µmol/L; thrombin receptor activating peptide (TRAP) 1 and 20 µmol/L; and a combination of collagen 5 µg/mL and epinephrine 5 µmol/L. Mean Florescence Intensity (MFI) is used as unit of measure. MFI indicates relative degree of shift in fluorescence intensity of a population of platelets in arbitrary units. |
Countries
United States
Participant flow
Recruitment details
Participants recruited at UMass Medical School in Worcester, MA between April 2008 and May 2009.
Pre-assignment details
15 healthy participants recruited; 16 screened, 1 excluded (1 did not meet inclusion criteria).
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive clopidogrel + aspirin first and placebo + aspirin first | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Customized Between 18 and 65 years | 15 participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change From Baseline in Platelet Surface Activated GPIIb-IIIa Complex at 45 Days After Intervention.
Value at 45 days after intervention minus value at baseline in platelet surface activated GPIIb-IIIa complex using flow cytometry.The types and concentrations of agonists used in the flow cytometry assays reported here were: ADP 0.5, 1, and 20 µmol/L; thrombin receptor activating peptide (TRAP) 1 and 20 µmol/L; and a combination of collagen 5 µg/mL and epinephrine 5 µmol/L. Mean Florescence Intensity (MFI) is used as unit of measure. MFI indicates relative degree of shift in fluorescence intensity of a population of platelets in arbitrary units.
Time frame: Baseline and 45 days after intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clopidogrel + Aspirin | Change From Baseline in Platelet Surface Activated GPIIb-IIIa Complex at 45 Days After Intervention. | 123.2 mean fluorescence intensity (MFI) | Standard Error 17.6 |
| Placebo + Aspirin | Change From Baseline in Platelet Surface Activated GPIIb-IIIa Complex at 45 Days After Intervention. | 126.7 mean fluorescence intensity (MFI) | Standard Error 17.9 |