Coronary Heart Disease, Platelet Aggregation Inhibitors
Conditions
Brief summary
One of the most common ways for preventing coronary heart disease (CHD) is to take aspirin or clopidogrel. However, studies have shown that not all people respond to these medications. The variance in treatment response may be linked to genetics. This study will examine the effects of aspirin and clopidogrel in a population whose genes are well known in order to determine the role that genes play in treatment responses.
Detailed description
CHD is the leading cause of death in the United States. Anti-platelet agents lessen platelet aggregation and are used commonly to prevent recurrent CHD events. Two of the most common anti-platelet agents are aspirin and clopidogrel. However, up to 25% to 30% of people do not respond to these medications. Evidence indicates that treatment response may be related to genetics. The purpose of this study is to determine specific gene variants that predict response to aspirin and clopidogrel therapy. This study is part of a larger group of studies called the Pharmacogenomics Research Network (PGRN). Participants will include the Old Order Amish of Lancaster, Pennsylvania. They are well suited for genetic studies because they are a homogenous, closed, founder population. Participants will receive 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants will take a single dose of 324 mg aspirin. Participants will undergo platelet function tests before and after clopidogrel alone, and then again after taking clopidogrel plus aspirin. Using the gene variation profiles across the genome, researchers will analyze which genes correspond to treatment response.
Interventions
DRUGClopidogrel
300 mg on first day, then 75 mg per day for the next 6 days
DRUGAspirin
Single dose of 324 mg on the last day of clopidogrel treatment
Sponsors
National Institute of General Medical Sciences (NIGMS)
National Heart, Lung, and Blood Institute (NHLBI)
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Of Old Order Amish descent
Exclusion criteria
* Currently pregnant or less than 6 months have passed since delivery * Has a history of a bleeding disorder or major spontaneous bleed, such as peptic ulcer, epistasis, or intracranial bleed * Has severe hypertension, defined by a blood pressure above 160/95 mm Hg, making it unethical not to recommend prompt treatment * Takes medications that would affect the outcome(s) to be measured and cannot willingly and safely, in the opinion of the treating physician and study physician, discontinue these medications for 1 week prior to protocol initiation * Is taking vitamins or other supplements and is unwilling to discontinue their use for at least 1 week prior to study * Has a coexisting malignancy * Has a creatinine level greater than 2.0 mg/dl, aspartate transaminase (AST) or alanine transaminase (ALT) greater than two times the upper limit of normal, hematocrit less than 32%, or a thyroid-stimulating hormone (TSH) less than 0.4 or greater than 5.5 mIU/L * Has a bleeding disorder or history of gastrointestinal bleeding or other major bleeding episode * Is currently taking aspirin, clopidogrel, or other anti-coagulant, such as warfarin, heparin, or GPIIb/IIIa antagonists, and have conditions that might place them at increased risk from withdrawal of these medications 14 days prior to protocol initiation, including history of unstable angina, heart attack, angioplasty (including stent placement), coronary artery bypass surgery, atrial fibrillation, stroke or transient ischemic attacks, diabetes, or deep vein thrombosis or other thrombosis * Has polycythemia, or thrombocytosis, defined by a platelet count greater than 500,000 * Has thrombocytopenia, defined by a platelet count less than 75,000 * Has had surgery within the last 6 months * Has an aspirin or clopidogrel allergy * Currently breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Platelet Function in Response to Clopidogrel | Measured at baseline, and after clopidogrel treatment | Baseline minus post clopidogrel/pre-aspirin platelet rich plasma (PRP) maximum aggregation. |
| Changes in Platelet Function in Response to Clopidogrel Plus Aspirin | Measured at baseline, and after clopidogrel plus aspirin treatment | Baseline minus post clopidogrel/post-aspirin platelet rich plasma (PRP) maximum aggregation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Participants will receive clopidogrel treatment alone, followed by clopidogrel plus aspirin treatment on the last day of treatment.
Clopidogrel: 300 mg on first day, then 75 mg per day for the next 6 days
Aspirin: Single dose of 324 mg on the last day of clopidogrel treatment | 682 |
| Total | 682 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Clopidogrel Plus Aspirin | Adverse Event | 2 |
| Clopidogrel Plus Aspirin | Physician Decision | 4 |
| Clopidogrel Treatment | Adverse Event | 6 |
| Clopidogrel Treatment | Physician Decision | 5 |
| Clopidogrel Treatment | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 13.5 |
| Region of Enrollment United States | 682 participants |
| Sex: Female, Male Female | 343 Participants |
| Sex: Female, Male Male | 339 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 682 |
| serious Total, serious adverse events | 0 / 682 |
Outcome results
Primary
Changes in Platelet Function in Response to Clopidogrel
Baseline minus post clopidogrel/pre-aspirin platelet rich plasma (PRP) maximum aggregation.
Time frame: Measured at baseline, and after clopidogrel treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Changes in Platelet Function in Response to Clopidogrel | PRP Collagen 5 | 14.06 percentage of maximum aggregation change | Standard Deviation 15.01 |
| Overall Study | Changes in Platelet Function in Response to Clopidogrel | PRP ADP 20 | 38.51 percentage of maximum aggregation change | Standard Deviation 14.3 |
Primary
Changes in Platelet Function in Response to Clopidogrel Plus Aspirin
Baseline minus post clopidogrel/post-aspirin platelet rich plasma (PRP) maximum aggregation
Time frame: Measured at baseline, and after clopidogrel plus aspirin treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Changes in Platelet Function in Response to Clopidogrel Plus Aspirin | PRP ADP 20 | 41.21 percentage of max aggregation change | Standard Deviation 13.09 |
| Overall Study | Changes in Platelet Function in Response to Clopidogrel Plus Aspirin | PRP Collagen 5 | 56.64 percentage of max aggregation change | Standard Deviation 14.44 |