Myocardial InfarctionPhase 2ELEVATENCT01235351
Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis In Myocardial Infarction 56
A Phase 2 study testing Clopidogrel in people with Myocardial Infarction and Percutaneous Coronary Intervention, run by The TIMI Study Group at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Myocardial Infarction, Percutaneous Coronary Intervention
- What is being tested?
- Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 335 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Sep 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Conditions that alter platelet function.
- Conditions that increase bleeding risk.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- Clopidogrel
- Keywords
- Myocardial infarction, Percutaneous coronary intervention, Clopidogrel, Genetics, Platelet Function
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClopidogrelDrug
Clopidogrel 75 mg daily, 150 mg daily, 225 mg daily, and 300 mg daily based on genotype
ClopidogrelDrug
Clopidogrel 75 mg daily, 150 mg daily
| Study group | Role | What they receive |
|---|---|---|
| Clopidogrel - for CYP2C19*2 carriers | Active comparator | Clopidogrel for CYP2C19*2 gene carriers Receives: Drug: Clopidogrel |
| Clopidogrel - for CYP2C19*2 non-carriers | Active comparator | Clopidogrel for CYP2C19*2 gene NON-carriers Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately every 2 weeks for 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2010 (estimated)
- Study startOct 2010
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 335 participants (actual)
Sponsor and investigators
- Lead sponsor
- The TIMI Study Group
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Sanofi
- Responsible party
- Sponsor
- Investigators
- Christian T Ruff, MD, MPH, Principal investigator, The TIMI Study Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01235351
- Sponsor's protocol ID
- TIMI 56
- Acronym
- ELEVATE
- Status last verified
- Nov 2019
- First submitted
- 2 Nov 2010
- Last updated
- 15 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22088980Hochholzer 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.
PubMed 25060370Carreras 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.
PubMed 27009617
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis In Myocardial Infarction 56
- ClinicalTrials.gov ID
- NCT01235351
- Acronym / sponsor ID
- ELEVATE / TIMI 56
- Keywords
- Myocardial infarction, Percutaneous coronary intervention, Clopidogrel, Genetics, Platelet Function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 335 participants (actual)
- Lead sponsor
- The TIMI Study GroupUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Sanofi
- Study start
- Oct 2010
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 5 Nov 2010 (estimated)
- Results
- Posted 15 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clopidogrel - for CYP2C19*2 carriers | Active comparator | Drug: ClopidogrelClopidogrel for CYP2C19*2 gene carriers |
| Clopidogrel - for CYP2C19*2 non-carriers | Active comparator | Drug: ClopidogrelClopidogrel for CYP2C19*2 gene NON-carriers |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (2 listed)
- Conditions that alter platelet function.
- Conditions that increase bleeding risk.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClopidogrelClopidogrel 75 mg daily, 150 mg daily, 225 mg daily, and 300 mg daily based on genotype | Drug | Clopidogrel - for CYP2C19*2 carriers |
| ClopidogrelClopidogrel 75 mg daily, 150 mg daily | Drug | Clopidogrel - for CYP2C19*2 non-carriers |
Primary outcome
Comparisons of Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation Platelet Reactivity Index (PRI)
Time frame: Approximately every 2 weeks for 8 weeks
The outcome measurement was on-treatment PRI determined through flow cytometric assessment of phosphorylation status of VASP.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22088980Mega 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 publication: PubMed 25060370Hochholzer 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 publication: PubMed 27009617Carreras 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian T Ruff, MD, MPH principal investigator
The TIMI Study Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clopidogrel in people with Myocardial Infarction and Percutaneous Coronary Intervention, run by The TIMI Study Group at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparisons of Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation Platelet Reactivity Index (PRI) (time frame: Approximately every 2 weeks for 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01235351, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2019.