Drug Action Increased
Conditions
Keywords
Clopidogrel, Aspirin, Interaction
Brief summary
Clopidogrel and aspirin are commonly used in combination to prevent heart attacks and to prevent blockage of stents. Both clopidogrel and aspirin work by preventing platelets (sticky cells that circulate in the blood) from forming blood clots in the arteries supplying oxygen to the heart and in stents. The investigators hypothesize that aspirin 325mg compared with aspirin 81 mg will increase blood levels of the active metabolite of clopidogrel in patients with a history of coronary artery disease who receive a 600mg loading dose of clopidogrel.
Detailed description
Eligible patients will be randomized to receive clopidogrel 600mg + aspirin 325mg (Group A) or clopidogrel 600mg + aspirin 81mg (Group B). Patients will be fasted for at least 8 hours prior to study drug administration. Blood samples will be collected at 1 hour after study drug administration for measurement of clopidogrel active metabolite levels and genotyping.
Interventions
DRUGClopidogrel
600mg (2 pills)
DRUGAspirin
325mg (1 pill)
Sponsors
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stable patients \>1 month post ACS (including ST elevated myocardial infarction, non-ST elevated myocardial infarction or unstable angina) or stent * Receiving regular ASA (81mg/d) and clopidogrel (75mg/d) for at least 1 week * Written informed consent
Exclusion criteria
* Age \< 18 years * Liver disease with ALT or bilirubin \>2x upper limits of normal (ULN)\* * Renal impairment with creatinine clearance \<30 ml/min\* * Deemed to be at high risk of bleeding (e.g., recent bleeding, platelet count\<100x109/L or hemoglobin \<100g/L)\* * Anticoagulant or NSAID therapy within the last 5 days * Antiplatelet agent other than aspirin and clopidogrel within the last 10 days * Uncontrolled hypertension (\>=180/110mmHg) * within 3 months of planned randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Concentration of the Active Metabolite of Clopidogrel | 1 hour after loading dose of study medications | Clopidogrel active metabolite concentration will be measured by liquid chromatography tandem mass spectrometry (LC/MS) methods. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Higher Dose Aspirin Group Clopidogrel 600 mg plus aspirin 325mg
Clopidogrel: 600mg (2 pills)
Aspirin: 325mg (1 pill) | 152 |
| Low Dose Aspirin Group Clopidogrel 600mg plus aspirin 81mg
Clopidogrel: 600mg (2 pills)
Aspirin: 81mg (1 pill) | 150 |
| Total | 302 |
Baseline characteristics
| Characteristic | Higher Dose Aspirin Group | Low Dose Aspirin Group | Total |
|---|---|---|---|
| Age, Continuous Age (years) | 59.3 years STANDARD_DEVIATION 9.3 | 61.5 years STANDARD_DEVIATION 10.4 | 60.4 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 37 Participants | 49 Participants | 86 Participants |
| Sex: Female, Male Male | 115 Participants | 101 Participants | 216 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 152 | 0 / 150 |
| other Total, other adverse events | 0 / 152 | 0 / 150 |
| serious Total, serious adverse events | 0 / 152 | 0 / 150 |
Outcome results
Primary
Blood Concentration of the Active Metabolite of Clopidogrel
Clopidogrel active metabolite concentration will be measured by liquid chromatography tandem mass spectrometry (LC/MS) methods.
Time frame: 1 hour after loading dose of study medications
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clopidogrel Concentration of Higher Dose Aspirin Group | Blood Concentration of the Active Metabolite of Clopidogrel | 14.45 ng/ml |
| Clopidogrel Concentration of Low Dose Aspirin Group | Blood Concentration of the Active Metabolite of Clopidogrel | 13.80 ng/ml |
p-value: 0.66t-test, 2 sided