Clopidogrel ResistancePhase 2NCT02008123
Effect of Primidone on Platelet Responsiveness in Patients Determined to be Clopidogrel Resistant
A Phase 2 study testing Primidone in people with Clopidogrel Resistance and Secondary Stroke Prevention, run by Dent Neuroscience Research Center at 1 site in United States.
Trial summary
The purpose of this study is to determine whether adding primidone will improve the metabolism of clopidogrel thereby increasing metabolite levels within the blood stream and platelet response to clopidogrel in patients who were previously found to lack adequate response to clopidogrel. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Clopidogrel Resistance, Secondary Stroke Prevention
- What is being tested?
- Primidone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Dec 2017
- Phase
- Phase 2
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females aged 18 - 90 years who are clopidogrel resistant as determined by whole blood aggregometry
- Patients with a low risk of new cerebrovascular ischemic events as indicated by an Essen Stroke Risk Score of less than three
Who cannot join
- Any history of allergy or intolerance to either Plavix or clopidogrel
- Any history of allergy or intolerance to either Mysoline or primidone
- Any clinically significant abnormalities in complete blood count as determined by the investigator
- Use of any acute medications within the last two weeks or initiation of any non-study medications during the study period that would effect CYP enzymes or platelet function
- Use of tobacco products from 2 weeks prior to enrollment in the study and throughout the duration of the study
- Any planned surgical procedures during the study or 5 days after the study has ended
Show all 13Show fewer
- History of alcoholism or alcohol abuse
- Participants who have had any alcohol consumption within 24 hours of a blood draw
- Previous stroke in past 3 months
- Participants who are or are planning to become pregnant
- Participants who of reproductive potential must agree to use a method of contraception for the duration of the study as well as 4 weeks after participation is complete
- Change in any medications that could affect liver enzymes or platelet aggregation throughout the study
- Compliance less than 80 % based on pill counts on two different study visits
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine whether adding primidone will improve the metabolism of clopidogrel thereby increasing metabolite levels within the blood stream and platelet response to clopidogrel in patients who were previously found to lack adequate response to clopidogrel. This information could help overcome clopidogrel resistance in patients who are at risk for stroke or transient ischemic attack (TIA).
- Being tested
- Primidone
- Keywords
- Clopidogrel, Clopidogrel Resistance, Primidone, Secondary Stroke Prevention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrimidoneDrug
Also called Mysoline (brand)
Primidone is an antiepileptic used for the management of generalized tonic-clonic seizures and for the management of complex partial seizures. One of primidone's active metabolite is phenobarbital, which is a potent cytochrome P450 inducer. In this study, primidone will be used to induce CYP 1A2 in order to provide more efficient metabolism of clopidogrel to its active form
| Study group | Role | What they receive |
|---|---|---|
| Primidone | Experimental | Participants will receive primidone in addition to their clopidogrel regimen. For the first 3 days of the study, participants will take 125 mg of primidone (one-half tablet). After 3 days of 125 mg, the primidone dose will be increased to 250 mg (1 tablet) taken at bedtime for the next 17-25 days. The participant will then be asked to return and be retested. Receives: Drug: Primidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet Aggregometry
Platelet Aggregometry will be used to assess platelet responsiveness to clopidogrel following treatment with investigational medication. Blood will be placed in plastic cuvettes and probes will be inserted. Wires on the probes measure platelet aggregation in electrical impedance. A baseline is obtained and then adenosine diphosphate (ADP) is added to cause aggregation. Clopidogrel prevents platelet aggregation through irreversible binding of its active metabolite to the ADP receptors on the platelet surface. The change in impedance from baseline is directly proportional to the extent of platelet aggregation and is expressed in ohms of resistance.
Measured: Platelet aggregometry will be performed at Visit 1 and Visit 2 which will be 20-28 days following Visit 1.
Secondary outcomes (1)
Area Under the Curve of Clopidogrel Metabolite Levels
Whole blood from the subjects will be drawn 30 minutes, 1 hour, 2 hours, 3 hours and 4 hours post clopidogrel dose. Once the blood is drawn, the metabolite will be derivatized to keep the metabolite stable in blood. Derivatization of the metabolite, involves spiking blood samples with 2-bromo-3'methoxyacetophenone contained in an acetonitrile solution. Once derivatization has been done, metabolite levels will be analyzed using liquid chromatography mass spectrometry (LCMS). Once concentration levels of the active metabolite are known, the area under the curve will be calculated under trapezoid rule (linear up, log down).
Measured: Metabolite Levels Drawn 30 minutes, 1 hour, 2 hours, 3 hours and 4 hours post clopidogrel dose at Visit 1 and Visit 2 which will be 20-28 days following Visit 1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2013 (estimated)
- Study startAug 2013
- Primary completionDec 2017 (estimated)
Why it stopped: Inclusion/Exclusion criteria was too stringent to enroll patients at this site.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clopidogrel ResistanceStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dent Neuroscience Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vernice Bates, M.D., Principal investigator, Dent Neurologic Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02008123
- Sponsor's protocol ID
- 434350-2
- Status last verified
- Aug 2016
- First submitted
- 6 Dec 2013
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Primidone on Platelet Responsiveness in Patients Determined to be Clopidogrel Resistant
- ClinicalTrials.gov ID
- NCT02008123
- Acronym / sponsor ID
- 434350-2
- Keywords
- Clopidogrel, Clopidogrel Resistance, Primidone, Secondary Stroke Prevention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Inclusion/Exclusion criteria was too stringent to enroll patients at this site.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Dent Neuroscience Research CenterUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Dec 2017 (estimated)
- First posted
- 11 Dec 2013 (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.
The purpose of this study is to determine whether adding primidone will improve the metabolism of clopidogrel thereby increasing metabolite levels within the blood stream and platelet response to clopidogrel in patients who were previously found to lack adequate response to clopidogrel. This information could help overcome clopidogrel resistance in patients who are at risk for stroke or transient ischemic attack (TIA).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Primidone | Experimental | Drug: PrimidoneParticipants will receive primidone in addition to their clopidogrel regimen. For the first 3 days of the study, participants will take 125 mg of primidone (one-half tablet). After 3 days of 125 mg, the primidone dose will be increased to 250 mg (1 tablet) taken at bedtime for the next 17-25 days. The participant will then be asked to return and be retested. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Males and females aged 18 - 90 years who are clopidogrel resistant as determined by whole blood aggregometry
- Patients with a low risk of new cerebrovascular ischemic events as indicated by an Essen Stroke Risk Score of less than three
Key exclusion criteria (13 listed)
- Any history of allergy or intolerance to either Plavix or clopidogrel
- Any history of allergy or intolerance to either Mysoline or primidone
- Any clinically significant abnormalities in complete blood count as determined by the investigator
- Use of any acute medications within the last two weeks or initiation of any non-study medications during the study period that would effect CYP enzymes or platelet function
- Use of tobacco products from 2 weeks prior to enrollment in the study and throughout the duration of the study
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 |
|---|---|---|
| PrimidoneAlso: Mysoline (brand)Primidone is an antiepileptic used for the management of generalized tonic-clonic seizures and for the management of complex partial seizures. One of primidone's active metabolite is phenobarbital, which is a potent cytochrome P450 inducer. In this study, primidone will be used to induce CYP 1A2 in order to provide more efficient metabolism of clopidogrel to its active form | Drug | Primidone |
Primary outcome
Platelet Aggregometry
Time frame: Platelet aggregometry will be performed at Visit 1 and Visit 2 which will be 20-28 days following Visit 1.
Platelet Aggregometry will be used to assess platelet responsiveness to clopidogrel following treatment with investigational medication. Blood will be placed in plastic cuvettes and probes will be inserted. Wires on the probes measure platelet aggregation in electrical impedance. A baseline is obtained and then adenosine diphosphate (ADP) is added to cause aggregation. Clopidogrel prevents platelet aggregation through irreversible binding of its active metabolite to the ADP receptors on the platelet surface. The change in impedance from baseline is directly proportional to the extent of platelet aggregation and is expressed in ohms of resistance.
1 secondary outcome
Area Under the Curve of Clopidogrel Metabolite Levels
Time frame: Metabolite Levels Drawn 30 minutes, 1 hour, 2 hours, 3 hours and 4 hours post clopidogrel dose at Visit 1 and Visit 2 which will be 20-28 days following Visit 1.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2016.
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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.
Vernice Bates, M.D. principal investigator
Dent Neurologic Institute
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 Primidone in people with Clopidogrel Resistance and Secondary Stroke Prevention, run by Dent Neuroscience Research Center 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 2 inclusion and 13 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: withdrawn, as of the sponsor's last update on 3 Aug 2016. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Platelet Aggregometry (time frame: Platelet aggregometry will be performed at Visit 1 and Visit 2 which will be 20-28 days following Visit 1.). 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 3 Aug 2016.