CLOPIDOGREL, POOR METABOLISM of (Disorder)Phase 2/3GI-CTNCT02048228
Genotyping Guided Individualized Treatment of Clopidogrel and Ticagrelor in ACS
A Phase 2/3 study testing genotyping guided therapy Ticagrelor, Clopidogrel and standard therapy clopidogrel in people with CLOPIDOGREL, POOR METABOLISM of (Disorder), run by Chinese PLA General Hospital at 1 site in China.
Trial summary
Clopidogrel, in addition to aspirin, is the cornerstone of therapy in patients suffering from Acute coronary syndrome. However, the platelet inhibitory response to clopidogrel varies substantially among individuals. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CLOPIDOGREL, POOR METABOLISM of (Disorder)
- What is being tested?
- genotyping guided therapy Ticagrelor, Clopidogrel and standard therapy clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- Oct 2014to Aug 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The diagnosis of ACS including unstable angina (UA),non-ST elevation myocardial infarction(NSTEMI),and ST-elevation MI (STEMI) is according to the American Heart Association/American College of Cardiology (AHA/ACC) criteria
Who cannot join
- known contraindication to dual anti-platelet therapy, history of chronic inflammatory disease, steroidal and non-steroidal anti-inflammatory drugs use, previous administration of antiplatelet drugs within 1 month before coronary artery angiography, illicit drug abuse, significant bleeding, cerebrovascular event within 3months, and/or major surgery within 4 weeks.
Trial locations and contacts
1 site in 1 country.
China1 site
General Hospital of Chinese People's Liberation Army
Beijing, 100853
Tong Yin, MD, PhD, +86-13693693085, yintong2000@yahoo.com
About this study
Official title: Study of Clopidogrel and Ticagrelor Anti-Platelet Treatment Using an Individualized Strategy Based on Genotyping in Chinese ACS Patients
Clopidogrel, in addition to aspirin, is the cornerstone of therapy in patients suffering from Acute coronary syndrome. However, the platelet inhibitory response to clopidogrel varies substantially among individuals. Several loss-of-function polymorphisms have been identified that may influence clinical outcome in patients presenting with acute coronary syndromes (ACS) who are treated with clopidogrel. However their contribution to high on-treatment platelet reactivity (HPR) in clopidogrel treated Chinese patients is less known. As far as we know, ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. we will conduct an interventional study to compare the antiplatelet efficiency between clopidogrel and ticagrelor by the guidance of CYP450 2C19*2 (CYP2C19*2) , using Taqman genotyping method.
Read the detailed description
Clopidogrel, in addition to aspirin, is the cornerstone of therapy in patients suffering from Acute coronary syndrome. However, the platelet inhibitory response to clopidogrel varies substantially among individuals. Several loss-of-function polymorphisms have been identified that may influence clinical outcome in patients presenting with acute coronary syndromes (ACS) who are treated with clopidogrel.
Mounting evidence suggests a crucial role for the loss-of-function CYP2C19*2 genetic variant. Carriers of CYP2C19*2 allele were at 30% higher risk for major adverse clinical events compared to non-carriers. CYP2C19*2 alone was also associated with increased mortality and stent thrombosis. These findings led the American Food and Drug Administration to issue a boxed warning for clopidogrel stating that poor metabolizers may not receive the full benefit of the drug. Thus, routine genotyping in the context of dual anti-platelet therapy is necessary.
Individual dual anti-platelet treatment is feasible to give the presence of treatment alternatives such as ticagrelor that is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel. Individualized administration of ticagrelor may have the potential to successfully minimize adverse ischemic events.
200 patients undergoing percutaneous coronary intervention (PCI) for treatment of non-ST-elevation acute coronary syndrome or stable coronary artery disease will be eligible for enrollment. Patients will be randomly assigned to a strategy of genotyping(using Taqman genotyping method) or standard treatment . CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers and patients in the standard treatment group will be given 75 mg clopidogrel daily. At the end of the 5 day antiplatelet treatment, efficacy of the treatment strategies will be evaluated using light transmittance aggregometry (LTA) method.
- Being tested
- genotyping guided therapy Ticagrelor, Clopidogrel, standard therapy clopidogrel
- Keywords
- Clopidogrel,, Pharmacogenetics,, Platelet reactivity,, CYP2C19,, point-of-care
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
genotyping guided therapy Ticagrelor, ClopidogrelDrug
Also called Ticagrelor, Clopidogrel
CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers and patients in the standard treatment group will be given 75 mg clopidogrel daily.
standard therapy clopidogrelDrug
Also called clopidogrel
All patients will be administrated with clopidogrel 75 mg daily for 5 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| genotyping guided therapy | Experimental | Patients randomized to the genotyping guided therapy arm will have their CYP2C19*2 carrier status determined at the time before antiplatelet therapy with subsequent alteration in antiplatelet therapy for *2 carriers.CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers will be given 75 mg clopidogrel daily. Receives: Drug: genotyping guided therapy Ticagrelor, Clopidogrel |
| Standard Therapy | Active comparator | Patients randomized to the Standard Therapy arm will not undergo genotyping. All patients will be administrated with clopidogrel 75 mg daily for 5 consecutive days. Receives: Drug: standard therapy clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clopidogrel response status as measured by the LTA assay in CYP2C19*2 carriers.
The primary endpoint is the proportion of CYP2C19*2 carriers with a platelet aggregation more than 59% after 5 days of antiplatelet therapy.The definition of high on-treatment platelet reactivity is derived from previous studies that had identified platelet aggregation more than 59% as optimum cutoff values for prediction of increased risk of major adverse cardiovascular events in Chinese patients.
Measured: Day 5 of enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2014 (estimated)
- Study startOct 2014
- Primary completionMar 2016 (estimated)
- Study completionAug 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CLOPIDOGREL, POOR METABOLISM of (Disorder)Studies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tong Yin, Chinese PLA General Hospital
- Investigators
- Tong Yin, MD, PhD, Principal investigator, Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02048228
- Sponsor's protocol ID
- NCT01417884
- Acronym
- GI-CT
- Status last verified
- Apr 2014
- First submitted
- 27 Jan 2014
- Last updated
- 11 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Clopidogrel and Ticagrelor Anti-Platelet Treatment Using an Individualized Strategy Based on Genotyping in Chinese ACS Patients
- ClinicalTrials.gov ID
- NCT02048228
- Acronym / sponsor ID
- GI-CT / NCT01417884
- Keywords
- Clopidogrel,, Pharmacogenetics,, Platelet reactivity,, CYP2C19,, point-of-care
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Mar 2016 (estimated)
- Study completion
- Aug 2016 (estimated)
- First posted
- 29 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clopidogrel, in addition to aspirin, is the cornerstone of therapy in patients suffering from Acute coronary syndrome. However, the platelet inhibitory response to clopidogrel varies substantially among individuals. Several loss-of-function polymorphisms have been identified that may influence clinical outcome in patients presenting with acute coronary syndromes (ACS) who are treated with clopidogrel. However their contribution to high on-treatment platelet reactivity (HPR) in clopidogrel treated Chinese patients is less known. As far as we know, ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. we will conduct an interventional study to compare the antiplatelet efficiency between clopidogrel and ticagrelor by the guidance of CYP450 2C19*2 (CYP2C19*2) , using Taqman genotyping method.
Detailed description
Clopidogrel, in addition to aspirin, is the cornerstone of therapy in patients suffering from Acute coronary syndrome. However, the platelet inhibitory response to clopidogrel varies substantially among individuals. Several loss-of-function polymorphisms have been identified that may influence clinical outcome in patients presenting with acute coronary syndromes (ACS) who are treated with clopidogrel.
Mounting evidence suggests a crucial role for the loss-of-function CYP2C19*2 genetic variant. Carriers of CYP2C19*2 allele were at 30% higher risk for major adverse clinical events compared to non-carriers. CYP2C19*2 alone was also associated with increased mortality and stent thrombosis. These findings led the American Food and Drug Administration to issue a boxed warning for clopidogrel stating that poor metabolizers may not receive the full benefit of the drug. Thus, routine genotyping in the context of dual anti-platelet therapy is necessary.
Individual dual anti-platelet treatment is feasible to give the presence of treatment alternatives such as ticagrelor that is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel. Individualized administration of ticagrelor may have the potential to successfully minimize adverse ischemic events.
200 patients undergoing percutaneous coronary intervention (PCI) for treatment of non-ST-elevation acute coronary syndrome or stable coronary artery disease will be eligible for enrollment. Patients will be randomly assigned to a strategy of genotyping(using Taqman genotyping method) or standard treatment . CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers and patients in the standard treatment group will be given 75 mg clopidogrel daily. At the end of the 5 day antiplatelet treatment, efficacy of the treatment strategies will be evaluated using light transmittance aggregometry (LTA) method.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| genotyping guided therapy | Experimental | Drug: genotyping guided therapy Ticagrelor, ClopidogrelPatients randomized to the genotyping guided therapy arm will have their CYP2C19*2 carrier status determined at the time before antiplatelet therapy with subsequent alteration in antiplatelet therapy for *2 carriers.CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers will be given 75 mg clopidogrel daily. |
| Standard Therapy | Active comparator | Drug: standard therapy clopidogrelPatients randomized to the Standard Therapy arm will not undergo genotyping. All patients will be administrated with clopidogrel 75 mg daily for 5 consecutive days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- The diagnosis of ACS including unstable angina (UA),non-ST elevation myocardial infarction(NSTEMI),and ST-elevation MI (STEMI) is according to the American Heart Association/American College of Cardiology (AHA/ACC) criteria
Key exclusion criteria (1 listed)
- known contraindication to dual anti-platelet therapy, history of chronic inflammatory disease, steroidal and non-steroidal anti-inflammatory drugs use, previous administration of antiplatelet drugs within 1 month before coronary artery angiography, illicit drug abuse, significant bleeding, cerebrovascular event within 3months, and/or major surgery within 4 weeks.
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 |
|---|---|---|
| genotyping guided therapy Ticagrelor, ClopidogrelAlso: Ticagrelor, ClopidogrelCYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers and patients in the standard treatment group will be given 75 mg clopidogrel daily. | Drug | genotyping guided therapy |
| standard therapy clopidogrelAlso: clopidogrelAll patients will be administrated with clopidogrel 75 mg daily for 5 consecutive days. | Drug | Standard Therapy |
Primary outcome
Clopidogrel response status as measured by the LTA assay in CYP2C19*2 carriers.
Time frame: Day 5 of enrollment
The primary endpoint is the proportion of CYP2C19*2 carriers with a platelet aggregation more than 59% after 5 days of antiplatelet therapy.The definition of high on-treatment platelet reactivity is derived from previous studies that had identified platelet aggregation more than 59% as optimum cutoff values for prediction of increased risk of major adverse cardiovascular events in Chinese patients.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2014.
Related trials for CLOPIDOGREL, POOR METABOLISM of (Disorder)
RecruitingObservational study
Multicentric Study on Clopidogrel Resistance in DAPT for CAS (MULTI-RESCLOSA)
Clopidogrel, Poor Metabolism of, Carotid Stenosis
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.
Tong Yin, MD, PhD principal investigator
Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing genotyping guided therapy Ticagrelor, Clopidogrel and standard therapy clopidogrel in people with CLOPIDOGREL, POOR METABOLISM of (Disorder), run by Chinese PLA General Hospital at 1 site in China.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 11 Apr 2014. 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 China. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tong Yin, MD, PhD (+86-13693693085, yintong2000@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clopidogrel response status as measured by the LTA assay in CYP2C19*2 carriers. (time frame: Day 5 of enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Apr 2014.