Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis In Myocardial Infarction 56 (ELEVATE)
Primary Purpose
Myocardial Infarction, Percutaneous Coronary Intervention
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Clopidogrel
Clopidogrel
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Infarction focused on measuring Myocardial infarction, Percutaneous coronary intervention, Clopidogrel, Genetics, Platelet Function
Eligibility Criteria
Inclusion Criteria (major):
- Between 18 and 75 years of age, inclusive.
- Have an indication for the use of clopidogrel defined as either spontaneous MI [hospitalized with final diagnosis of MI, excluding periprocedural or definite secondary MI (e.g., due to anemia or hypertensive emergency)] or PCI within the past 6 months.
- Clinically stable and at least 4 weeks following the MI or PCI.
Exclusion Criteria (major):
- Conditions that alter platelet function.
- Conditions that increase bleeding risk.
Sites / Locations
- TIMI Study Group
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Clopidogrel - for CYP2C19*2 carriers
Clopidogrel - for CYP2C19*2 non-carriers
Arm Description
Clopidogrel for CYP2C19*2 gene carriers
Clopidogrel for CYP2C19*2 gene NON-carriers
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01235351
First Posted
November 2, 2010
Last Updated
November 13, 2019
Sponsor
The TIMI Study Group
Collaborators
Bristol-Myers Squibb, Sanofi
1. Study Identification
Unique Protocol Identification Number
NCT01235351
Brief Title
Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis In Myocardial Infarction 56
Acronym
ELEVATE
Official Title
Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis In Myocardial Infarction 56
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The TIMI Study Group
Collaborators
Bristol-Myers Squibb, Sanofi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction, Percutaneous Coronary Intervention
Keywords
Myocardial infarction, Percutaneous coronary intervention, Clopidogrel, Genetics, Platelet Function
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
335 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Clopidogrel - for CYP2C19*2 carriers
Arm Type
Active Comparator
Arm Description
Clopidogrel for CYP2C19*2 gene carriers
Arm Title
Clopidogrel - for CYP2C19*2 non-carriers
Arm Type
Active Comparator
Arm Description
Clopidogrel for CYP2C19*2 gene NON-carriers
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Intervention Description
Clopidogrel 75 mg daily, 150 mg daily, 225 mg daily, and 300 mg daily based on genotype
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Intervention Description
Clopidogrel 75 mg daily, 150 mg daily
Primary Outcome Measure Information:
Title
Comparisons of Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation Platelet Reactivity Index (PRI)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (major):
Between 18 and 75 years of age, inclusive.
Have an indication for the use of clopidogrel defined as either spontaneous MI [hospitalized with final diagnosis of MI, excluding periprocedural or definite secondary MI (e.g., due to anemia or hypertensive emergency)] or PCI within the past 6 months.
Clinically stable and at least 4 weeks following the MI or PCI.
Exclusion Criteria (major):
Conditions that alter platelet function.
Conditions that increase bleeding risk.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian T Ruff, MD, MPH
Organizational Affiliation
TIMI Study Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
TIMI Study Group
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22088980
Citation
Mega JL, Hochholzer W, Frelinger AL 3rd, Kluk MJ, Angiolillo DJ, Kereiakes DJ, Isserman S, Rogers WJ, Ruff CT, Contant C, Pencina MJ, Scirica BM, Longtine JA, Michelson AD, Sabatine MS. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. JAMA. 2011 Nov 23;306(20):2221-8. doi: 10.1001/jama.2011.1703. Epub 2011 Nov 16.
Results Reference
result
PubMed Identifier
25060370
Citation
Hochholzer W, Ruff CT, Mesa RA, Mattimore JF, Cyr JF, Lei L, Frelinger AL 3rd, Michelson AD, Berg DD, Angiolillo DJ, O'Donoghue ML, Sabatine MS, Mega JL. Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial. J Am Coll Cardiol. 2014 Jul 29;64(4):361-8. doi: 10.1016/j.jacc.2014.03.051.
Results Reference
result
PubMed Identifier
27009617
Citation
Carreras ET, Hochholzer W, Frelinger AL 3rd, Nordio F, O'Donoghue ML, Wiviott SD, Angiolillo DJ, Michelson AD, Sabatine MS, Mega JL. Diabetes mellitus, CYP2C19 genotype, and response to escalating doses of clopidogrel. Insights from the ELEVATE-TIMI 56 Trial. Thromb Haemost. 2016 Jul 4;116(1):69-77. doi: 10.1160/TH15-12-0981. Epub 2016 Mar 24.
Results Reference
result
Learn more about this trial
Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis In Myocardial Infarction 56
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