A Phase 2 interventional study of Clopidogrel and Clopidogrel in Myocardial Infarction and Percutaneous Coronary Intervention, sponsored by The TIMI Study Group. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2019-11-15.
Sponsored by The TIMI Study Group · Phase 2, Interventional, and Treatment
To determine whether higher as compared with lower maintenance doses of clopidogrel can adequately improve the degree of platelet inhibition in carriers of a reduced-function CYP2C19 allele.
Clopidogrel blocks the P2Y12 ADP receptor on platelets and has been shown to reduce cardiovascular events in acute coronary syndrome (ACS) patients.However, inter-patient variability in the pharmacodynamic response to clopidogrel is well recognized, and patients with lesser degrees of platelet inhibition in response to clopidogrel have been shown to be at increased risk of cardiovascular events.
One potential source of this variability is the metabolism of clopidogrel, which is a pro-drug requiring biotransformation to become an active antiplatelet compound. Cytochrome P-450 (CYP) enzymes play a role in the metabolism, and carriers of reduced-function genetic variants in CYP2C19 (\~30% of the population) have lower active clopidogrel metabolite levels, diminished platelet inhibition, and higher rates of adverse cardiovascular events as compared with non-carriers in the setting of treatment with standard maintenance doses of clopidogrel.
Aim: To determine whether higher as compared with lower maintenance doses of clopidogrel can adequately improve the degree of platelet inhibition in carriers of a reduced-function CYP2C19 allele.
Hypotheses: The primary hypothesis is that subjects who carry a reduced-function CYP2C19 allele will have improvement in platelet inhibition with higher maintenance doses of clopidogrel.The secondary hypothesis is that higher maintenance doses of clopidogrel in carriers of a reduced-function CYP2C19 allele will result in similar platelet inhibition as compared to a standard maintenance dose of clopidogrel in non-carriers.
2,744 studies on the registry are indexed under Myocardial Infarction; 418 are open to participants now.
This study's enrollment of 335 is above the median of 148 across 1,595 interventional studies indexed under Myocardial Infarction.
Browse Myocardial Infarction studies →The TIMI Study Group is the lead sponsor of 3 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria (major):
Clopidogrel for CYP2C19\*2 gene carriers
Drug: Clopidogrel
Clopidogrel for CYP2C19\*2 gene NON-carriers
Drug: Clopidogrel
Clopidogrel 75 mg daily, 150 mg daily, 225 mg daily, and 300 mg daily based on genotype
Clopidogrel 75 mg daily, 150 mg daily
Comparisons of Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation Platelet Reactivity Index (PRI)
The outcome measurement was on-treatment PRI determined through flow cytometric assessment of phosphorylation status of VASP.
Time frame: Approximately every 2 weeks for 8 weeks
335 patients from 32 sites were enrolled from October 2010 until September 2011.
| Milestone | CYP2C19*2 Non-Carrier | CYP2C19*2 Carrier |
|---|---|---|
| Started | 247 | 86 |
| Completed | 237 | 82 |
| Not completed | 10 | 4 |
| Withdrew: No follow-up sample | 10 | 4 |
| Milestone | CYP2C19*2 Non-Carrier | CYP2C19*2 Carrier |
|---|---|---|
| Started | 233 | 82 |
| 75 mg first and then 150 mg | 116 | 0 |
| 150 mg first then 75 mg | 117 | 0 |
| 225 mg first then 300 mg | 0 | 41 |
| 300 mg first then 225 mg | 0 | 41 |
| Completed | 233 | 82 |
| Not completed | 0 | 0 |
The outcome measurement was on-treatment PRI determined through flow cytometric assessment of phosphorylation status of VASP.
| % of PRI | CYP2C19*2 Carriers | CYP2C19*2 Non-Carriers |
|---|---|---|
| Clopidogrel 75 mg | 71.0 (67.1 to 74.9) | 57.5 (55.1 to 59.9) |
| Clopidogrel 150 mg | 62.4 (58.1 to 66.7) | 46.9 (44.3 to 49.1) |
| Clopidogrel 225 mg | 54.0 (49.4 to 58.5) | — |
| Clopidogrel 300 mg | 50.1 (45.9 to 54.3) | — |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| CYP2C19*2 Carriers 75 mg | — | 1/82 (1.2%) | 0/82 (0%) |
| CYP2C19*2 Carriers 150 mg | — | 5/82 (6.1%) | 0/82 (0%) |
| CYP2C19*2 Carriers 225 mg | — | 0/82 (0%) | 0/82 (0%) |
| CYP2C19*2 Carriers 300mg | — | 0/82 (0%) | 0/82 (0%) |
| CYP2C19*2 Noncarriers 75 mg | — | 24/233 (10.3%) | 0/233 (0%) |
| CYP2C19*2 Noncarriers 150 mg | — | 16/233 (6.9%) | 0/233 (0%) |
| Event | CYP2C19*2 Carriers 75 mg | CYP2C19*2 Carriers 150 mg | CYP2C19*2 Carriers 225 mg | CYP2C19*2 Carriers 300mg | CYP2C19*2 Noncarriers 75 mg | CYP2C19*2 Noncarriers 150 mg |
|---|---|---|---|---|---|---|
| Vascular disordersVascular disorders | 0/82 | 5/82 | 0/82 | 0/82 | 16/233 | 11/233 |
| Cardiac disordersCardiac disorders | 1/82 | 0/82 | 0/82 | 0/82 | 4/233 | 3/233 |
| General disorders and administration site conditionsGeneral disorders | 0/82 | 0/82 | 0/82 | 0/82 | 3/233 | 1/233 |
| Infections and infestationsInfections and infestations | 0/82 | 0/82 | 0/82 | 0/82 | 1/233 | 1/233 |
| Blood and lymphatic system disorderBlood and lymphatic system disorders | 0/82 | 0/82 | 0/82 | 0/82 | 0/233 | 0/233 |
| Gastrointestinal disordersGastrointestinal disorders | 0/82 | 0/82 | 0/82 | 0/82 | 0/233 | 0/233 |
| Injury, poisoning and procedural complicationsInjury, poisoning and procedural complications | 0/82 | 0/82 | 0/82 | 0/82 | 0/233 | 0/233 |
| Respiratory, thoracic and mediastinal disordersRespiratory, thoracic and mediastinal disorders | 0/82 | 0/82 | 0/82 | 0/82 | 0/233 | 0/233 |
| Age, Continuous(years) | CYP2C19*2 Non-Carriers | CYP2C19*2 Carriers | Total |
|---|---|---|---|
| Mean Age | 60.8 ± 9.9 | 58.6 ± 9.7 | 60.2 ± 9.9 |
| Sex: Female, Male(Participants) | CYP2C19*2 Non-Carriers | CYP2C19*2 Carriers | Total |
|---|---|---|---|
| Female | 61 | 23 | 84 |
| Male | 186 | 63 | 249 |
This study is completed, as verified in Nov 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
The TIMI Study Group