Ischemic StrokePhase 4CLOGISNCT03385538
Clopidogrel Response and CYP2C19 Genotype in Ischemic Stroke Patients
A Phase 4 study testing Clopidogrel in people with Ischemic Stroke, run by Zealand University Hospital at 1 site in Denmark.
Trial summary
Personalized therapy as prophylaxis in ischemic stroke patients is not yet an option. From patients with ischemic heart disease, we know that patients with in vitro high on treatment platelet reactivity (HTPR) have an increased risk of stent thrombosis following per-cutaneous coronary intervention. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Nov 2015to 30 Jul 2017
- Phase
- Phase 4
- 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
- Ischemic stroke diagnosis
- treatment with clopidogrel 75 mg/day
Who cannot join
- increased risk of bleeding
- treatment with NOAC, vitamin K antagonist or other antiplatelet drug than clopidogrel
- unable to give informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Personalized therapy as prophylaxis in ischemic stroke patients is not yet an option. From patients with ischemic heart disease, we know that patients with in vitro high on treatment platelet reactivity (HTPR) have an increased risk of stent thrombosis following per-cutaneous coronary intervention. Other studies have shown association of CYP2C19 genotypes with different responses to the anti platelet drug Clopidogrel. We measure HTPR in ischemic stroke patients on increasing doses of clopidogrel and investigate the CYP2C19 genotype for each patient.
Read the detailed description
Background: Clopidogrel (CLO) is a pro-drug metabolized in the liver by the Cytochrom-P450 system to its active component. Studies in acute ischemic stroke (IS) patients have proven that genetic differences in coding of an enzyme responsible for the metabolism of CLO (CYP2C19) results in different response to CLO when tested in the blood. An American study in cardiac patients have shown an association between the genotype and the CLO-response to different dosages of CLO, meaning that patients who are non-responders to low dosages of CLO may be responders to higher CLO dosages. Furthermore, the study showed that patients with a distinct genotype does not gain CLO response even at high CLO dosages (300 mg/day).
Perspective: The study will have an impact on the patient, the relatives and the social economy. The project answers if it is possible to give personalized therapy to IS patients securing the best possible prophylactic treatment for each single patient. Hereby reducing the risk of early death, disability and dependency. The project determines the genetic distribution of CYP2C19 alleles in the Danish IS population and determine the association between genotype and CLO-response in clinically relevant dosages in a Caucasian population of IS patients.
Objective: To determine the correlation between genotype and Clopidogrel response to different CLO dosage and to determine the distribution of different alleles of CYP2C19 genotypes in a Danish IS population.
Hypothesis: CLO response is determined by CYP2C19 genotype, and there is a correlation between drug-response and CYP2C19 genotype.
Method: Systematic recording of data on 103 IS patients receiving prophylactic treatment with CLO 75 mg/day.
Genotype is determined in collaboration with Division of Clinical Biochemistry, Dept. of Diagnostics, Glostrup Hospital determining the CYP2C19 genotype *1(wild-type), *2(Loss Of Function=LOF) and *17(Gain Of Function=GOF). CLO responder status is determined using the VerifyNow P2Y12 assays.
Patients receiving CLO 75 mg/day who are non-responders when testing with VerifyNow P2Y12 assays have a blood sample for genetic testing. Patients carrying the *2 genotype on one or both alleles are CLO responder status tested on increasing doses of CLO, rising 75 mg/day every 14 days (150/225/300 mg) until maximum CLO 300 mg/day. Responder status is tested at the end of every second week, before increasing dosage. If the patient is CLO responder on the tested dose (150/225/300 mg) or non-responder on CLO 300 mg/day, the patient is ended in the study and switched to treatment with ASA in combination with Dipyramidole.
- Conditions
- Ischemic Stroke
- Being tested
- Clopidogrel
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClopidogrelDrug
increasing doses of clopidogrel depending on PRU values (75-300 mg)
| Study group | Role | What they receive |
|---|---|---|
| Clopidogrel non-responders | Experimental | Increasing doses og Clopidogrel depending on PRU values measured on VerifyNow Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients who has clopidogrel HTPR
Clopidogrel responder status measured with VerifyNow
Measured: 7 days
Number of patients who are carriers of CYP2C19 loss-of-function alleles
Genotyping patients for different loss-of-function CYP2C19 alleeles (*2, *3)
Measured: 1 day
Number of patients who are carriers of P2Y12-receptor loss-of-function alleles
genotyping patients for different loss-of-function P2Y12 receptor alleeles
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2017
- Study start1 Nov 2015
- Primary completion30 Jul 2017
- Study completion30 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Zealand University 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 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charlotte Rath, MD, Principal investigator, Zealand University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03385538
- Sponsor's protocol ID
- 2015-003548-38
- Other IDs
- 2015
- Acronym
- CLOGIS
- Status last verified
- Dec 2017
- First submitted
- 21 Aug 2017
- Last updated
- 28 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clopidogrel Response and CYP2C19 Genotype in Ischemic Stroke Patients
- ClinicalTrials.gov ID
- NCT03385538
- Acronym / sponsor ID
- CLOGIS / 2015-003548-38
- Conditions
- Ischemic Stroke
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Study start
- 1 Nov 2015 (actual)
- Primary completion
- 30 Jul 2017 (actual)
- Study completion
- 30 Jul 2017 (actual)
- First posted
- 28 Dec 2017 (actual)
- 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.
Personalized therapy as prophylaxis in ischemic stroke patients is not yet an option. From patients with ischemic heart disease, we know that patients with in vitro high on treatment platelet reactivity (HTPR) have an increased risk of stent thrombosis following per-cutaneous coronary intervention. Other studies have shown association of CYP2C19 genotypes with different responses to the anti platelet drug Clopidogrel. We measure HTPR in ischemic stroke patients on increasing doses of clopidogrel and investigate the CYP2C19 genotype for each patient.
Detailed description
Background: Clopidogrel (CLO) is a pro-drug metabolized in the liver by the Cytochrom-P450 system to its active component. Studies in acute ischemic stroke (IS) patients have proven that genetic differences in coding of an enzyme responsible for the metabolism of CLO (CYP2C19) results in different response to CLO when tested in the blood. An American study in cardiac patients have shown an association between the genotype and the CLO-response to different dosages of CLO, meaning that patients who are non-responders to low dosages of CLO may be responders to higher CLO dosages. Furthermore, the study showed that patients with a distinct genotype does not gain CLO response even at high CLO dosages (300 mg/day).
Perspective: The study will have an impact on the patient, the relatives and the social economy. The project answers if it is possible to give personalized therapy to IS patients securing the best possible prophylactic treatment for each single patient. Hereby reducing the risk of early death, disability and dependency. The project determines the genetic distribution of CYP2C19 alleles in the Danish IS population and determine the association between genotype and CLO-response in clinically relevant dosages in a Caucasian population of IS patients.
Objective: To determine the correlation between genotype and Clopidogrel response to different CLO dosage and to determine the distribution of different alleles of CYP2C19 genotypes in a Danish IS population.
Hypothesis: CLO response is determined by CYP2C19 genotype, and there is a correlation between drug-response and CYP2C19 genotype.
Method: Systematic recording of data on 103 IS patients receiving prophylactic treatment with CLO 75 mg/day.
Genotype is determined in collaboration with Division of Clinical Biochemistry, Dept. of Diagnostics, Glostrup Hospital determining the CYP2C19 genotype *1(wild-type), *2(Loss Of Function=LOF) and *17(Gain Of Function=GOF). CLO responder status is determined using the VerifyNow P2Y12 assays.
Patients receiving CLO 75 mg/day who are non-responders when testing with VerifyNow P2Y12 assays have a blood sample for genetic testing. Patients carrying the *2 genotype on one or both alleles are CLO responder status tested on increasing doses of CLO, rising 75 mg/day every 14 days (150/225/300 mg) until maximum CLO 300 mg/day. Responder status is tested at the end of every second week, before increasing dosage. If the patient is CLO responder on the tested dose (150/225/300 mg) or non-responder on CLO 300 mg/day, the patient is ended in the study and switched to treatment with ASA in combination with Dipyramidole.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clopidogrel non-responders | Experimental | Drug: ClopidogrelIncreasing doses og Clopidogrel depending on PRU values measured on VerifyNow |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Ischemic stroke diagnosis
- treatment with clopidogrel 75 mg/day
Key exclusion criteria (3 listed)
- increased risk of bleeding
- treatment with NOAC, vitamin K antagonist or other antiplatelet drug than clopidogrel
- unable to give informed consent
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 |
|---|---|---|
| Clopidogrelincreasing doses of clopidogrel depending on PRU values (75-300 mg) | Drug | Clopidogrel non-responders |
Primary outcome
Number of patients who has clopidogrel HTPR
Time frame: 7 days
Clopidogrel responder status measured with VerifyNow
Number of patients who are carriers of CYP2C19 loss-of-function alleles
Time frame: 1 day
Genotyping patients for different loss-of-function CYP2C19 alleeles (*2, *3)
Number of patients who are carriers of P2Y12-receptor loss-of-function alleles
Time frame: 1 day
genotyping patients for different loss-of-function P2Y12 receptor alleeles
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- Individual participant dataSharing planned: No
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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.
Charlotte Rath, MD principal investigator
Zealand University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clopidogrel in people with Ischemic Stroke, run by Zealand University Hospital at 1 site in Denmark.
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 2 inclusion and 3 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 28 Dec 2017. 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 Denmark. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients who has clopidogrel HTPR (time frame: 7 days). The study lists 3 primary outcomes in all. 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 28 Dec 2017.