Clinical trial NCT01341964: Clopidogrel and Aspirin Interaction Study-2
Official title: Randomized Controlled Trial to Explore Interaction Between Aspirin and Clopidogrel in Stable Patients With Previous Myocardial Infarction or Coronary Artery Stent
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Drug Action Increased
Keywords: Clopidogrel
Aspirin
Interaction
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2011-04-26
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Blood Concentration of the Active Metabolite of Clopidogrel
timeFrame: 1 hour after loading dose of study medications
Secondary outcomes:
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Population Health Research Institute, Hamilton General Hospital
state: Ontario
Study officials:
affiliation: Population Health Research Institute
name: Yan Liang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Population Health Research Institute
name: John Eikelboom, MD
role: STUDY_DIRECTOR
References:
citation: Liang Y, Hirsh J, Weitz JI, Sloane D, Gao P, Pare G, Zhu J, Eikelboom JW. Active metabolite concentration of clopidogrel in patients taking different doses of aspirin: results of the interaction trial. J Thromb Haemost. 2015 Mar;13(3):347-52. doi: 10.1111/jth.12829. Epub 2015 Feb 4.