Disease SusceptibilityPhase 2NCT01097343
Clopidogrel Pharmacogenomics Project
A Phase 2 study testing clopidogrel 75 mg and Clopidogrel 150 mg in people with Disease Susceptibility, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
Loss-of-function mutation of the gene encoding the CYP450 2C19 enzyme has emerged as a likely determinant of resistance to clopidogrel therapy. The primary hypothesis of the proposed research is that among patients with confirmed loss-of-function alleles of the CYP2C19 gene, increasing the maintenance clopidogrel dose… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Disease Susceptibility
- What is being tested?
- clopidogrel 75 mg and Clopidogrel 150 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to May 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria:• Currently taking clopidogrel 75 mg/day and aspirin (minimum 81 mg/day) with an indication for chronic dual antiplatelet therapy (>90 days)
- No evidence of acute coronary syndrome within 30 days of enrollment, defined by elevation of Troponin I above the upper limit of normal
- Coronary atherosclerosis documented on previous coronary angiogram
- No known contraindications to combination therapy with aspirin and clopidogrel
- Prognosis for survival greater than one year based on physician's assessment
- Able to attend all scheduled visits.
- Access to phone
- Subject is a female with a negative urine or serum pregnancy test or post-menopausal for at least 1 year prior to randomization. Females of childbearing potential must be practicing adequate birth control to be eligible. It is the Investigator's responsibility for determining whether the Subject has adequate birth control for study participation
Exclusion Criteria:• Recent acute coronary syndrome (<30 days)
- Recent hospitalization or physician visit for bleeding disorder(<90 days) or history of chronic blood loss
- Recent blood transfusion (<90 days)
- Any contraindication to aspirin or clopidogrel therapy
- Acute Febrile illness at the time of enrollment
- Subject is pregnant or lactating or planning to become pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina
Chapel Hill, North Carolina, 27599
About this study
Loss-of-function mutation of the gene encoding the CYP450 2C19 enzyme has emerged as a likely determinant of resistance to clopidogrel therapy. The primary hypothesis of the proposed research is that among patients with confirmed loss-of-function alleles of the CYP2C19 gene, increasing the maintenance clopidogrel dose from 75 to 150 mg will result in significant reduction in the rate of measured clopidogrel resistance defined by multiple measures of platelet function
Read the detailed description
The first phase of the clinical trial will involve subject recruitment and informed consent for genetic testing. Because the target population is patients with stable coronary artery disease, patients will be recruited from the outpatient setting during clinic visits or at the time of outpatient cardiac catheterization. It is expected that all potential candidates will be initially screened for eligibility by their treating cardiologist. If a patient agrees to undergo formal screening, they will be approached by a member of the research team and receive a written summary of the clinical trial protocol that will be reviewed with the trial personnel. The initial informed consent will allow the patient to undergo genetic testing and baseline VerifyNow assay, and will also give the trial personnel permission to contact the patient by phone if they are found to be eligible for the interventional phase of the trial. The goal for enrollment in the genetic testing portion of this clinical trial is 200 patients.
If the genetic testing results confirm that the patient is a candidate for the interventional study, they will be contacted and asked to make an outpatient appointment to initiate the interventional study protocol. The therapeutic portion of this study will be a randomized, unblinded cross-over comparison of two clopidogrel dosing strategies. It is anticipated that all eligible patients will have continued their previous chronic clopidogrel therapy with standard dosing of 75 mg/day. Because all patients will be receiving chronic clopidogrel at the initiation of the intervention protocol, steady state levels should be present in all patients. Dose dependent inhibition of platelet aggregation can be seen two hours after a single oral dose of clopidogrel. Repeated doses of 75mg daily produce steady state inhibition between day 3 and day 7 of administration.
Patients who agree to participate in the therapeutic protocol, and who meet the eligibility criteria, will be randomized to an initial dosing strategy of 75 or 150 mg daily for a minimum of 30 days. At day 30 (+/- 5 days), patients will return for repeat platelet function testing. In a randomly selected subset of 15 patients, blood will be tested for the active metabolite of clopidogrel. At that time, there will be a crossover with those patients receiving 75 mg qD increased to 150 mg qD and those receiving 150 mg qD decreased to 75 mg qD. At day 60 (+/- 5 days), participants will again return for comprehensive platelet function testing and a second randomly selected group of patients will undergo testing for clopidogrel metabolites. Chronic clopidogrel dosing will be reduced to 75mg in all participants. Please see the attached schedule of events for a summary of the trial schedule.
- Conditions
- Disease Susceptibility
- Being tested
- clopidogrel 75 mg, Clopidogrel 150 mg
- Keywords
- Clopidogrel pharmacogenomics study, Performing genetic study looking at clopidogrel resistance
- Medical subject headings
- Disease Susceptibility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clopidogrel 75 mgDrug
Also called Plavix
75 mg once daily
Clopidogrel 150 mgDrug
Also called Plavix
clopidogrel 150 mg
| Study group | Role | What they receive |
|---|---|---|
| 75 mg clopidogrel | Active comparator | Not described Receives: Drug: clopidogrel 75 mg |
| 150 mg clopidogrel | Active comparator | Not described Receives: Drug: Clopidogrel 150 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clopidogrel Resistance, Defined by P2Y12 Reaction Units (PRU)Value >230
P2Y12 Reaction Units are measured using the VerifyNow P2Y12 assay. Percent of patients with clopidogrel resistance defined by PRU value will be compared among low and high dose clopidogrel groups after 30 days of therapy.
Measured: Approximately 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2010 (estimated)
- Study startMar 2010
- Primary completionApr 2011
- Study completionMay 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.
- Other trials for Disease SusceptibilityStudies 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joseph Rossi, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01097343
- Sponsor's protocol ID
- 09-2104
- Status last verified
- Feb 2014
- First submitted
- 30 Mar 2010
- Last updated
- 12 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clopidogrel Pharmacogenomics Project
- ClinicalTrials.gov ID
- NCT01097343
- Acronym / sponsor ID
- 09-2104
- Conditions
- Disease Susceptibility
- Keywords
- Clopidogrel pharmacogenomics study, Performing genetic study looking at clopidogrel resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Apr 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 1 Apr 2010 (estimated)
- Results
- Posted 26 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Loss-of-function mutation of the gene encoding the CYP450 2C19 enzyme has emerged as a likely determinant of resistance to clopidogrel therapy. The primary hypothesis of the proposed research is that among patients with confirmed loss-of-function alleles of the CYP2C19 gene, increasing the maintenance clopidogrel dose from 75 to 150 mg will result in significant reduction in the rate of measured clopidogrel resistance defined by multiple measures of platelet function
Detailed description
The first phase of the clinical trial will involve subject recruitment and informed consent for genetic testing. Because the target population is patients with stable coronary artery disease, patients will be recruited from the outpatient setting during clinic visits or at the time of outpatient cardiac catheterization. It is expected that all potential candidates will be initially screened for eligibility by their treating cardiologist. If a patient agrees to undergo formal screening, they will be approached by a member of the research team and receive a written summary of the clinical trial protocol that will be reviewed with the trial personnel. The initial informed consent will allow the patient to undergo genetic testing and baseline VerifyNow assay, and will also give the trial personnel permission to contact the patient by phone if they are found to be eligible for the interventional phase of the trial. The goal for enrollment in the genetic testing portion of this clinical trial is 200 patients.
If the genetic testing results confirm that the patient is a candidate for the interventional study, they will be contacted and asked to make an outpatient appointment to initiate the interventional study protocol. The therapeutic portion of this study will be a randomized, unblinded cross-over comparison of two clopidogrel dosing strategies. It is anticipated that all eligible patients will have continued their previous chronic clopidogrel therapy with standard dosing of 75 mg/day. Because all patients will be receiving chronic clopidogrel at the initiation of the intervention protocol, steady state levels should be present in all patients. Dose dependent inhibition of platelet aggregation can be seen two hours after a single oral dose of clopidogrel. Repeated doses of 75mg daily produce steady state inhibition between day 3 and day 7 of administration.
Patients who agree to participate in the therapeutic protocol, and who meet the eligibility criteria, will be randomized to an initial dosing strategy of 75 or 150 mg daily for a minimum of 30 days. At day 30 (+/- 5 days), patients will return for repeat platelet function testing. In a randomly selected subset of 15 patients, blood will be tested for the active metabolite of clopidogrel. At that time, there will be a crossover with those patients receiving 75 mg qD increased to 150 mg qD and those receiving 150 mg qD decreased to 75 mg qD. At day 60 (+/- 5 days), participants will again return for comprehensive platelet function testing and a second randomly selected group of patients will undergo testing for clopidogrel metabolites. Chronic clopidogrel dosing will be reduced to 75mg in all participants. Please see the attached schedule of events for a summary of the trial schedule.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 75 mg clopidogrel | Active comparator | Drug: clopidogrel 75 mg |
| 150 mg clopidogrel | Active comparator | Drug: Clopidogrel 150 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| clopidogrel 75 mgAlso: Plavix75 mg once daily | Drug | 75 mg clopidogrel |
| Clopidogrel 150 mgAlso: Plavixclopidogrel 150 mg | Drug | 150 mg clopidogrel |
Primary outcome
Clopidogrel Resistance, Defined by P2Y12 Reaction Units (PRU)Value >230
Time frame: Approximately 90 days
P2Y12 Reaction Units are measured using the VerifyNow P2Y12 assay. Percent of patients with clopidogrel resistance defined by PRU value will be compared among low and high dose clopidogrel groups after 30 days of therapy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Joseph Rossi, MD principal investigator
University of North Carolina, Chapel Hill
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 75 mg and Clopidogrel 150 mg in people with Disease Susceptibility, run by University of North Carolina, Chapel Hill 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?
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 12 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 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 26 Mar 2014). 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?
Clopidogrel Resistance, Defined by P2Y12 Reaction Units (PRU)Value >230 (time frame: Approximately 90 days). 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 12 Dec 2017.