Coronary Artery DiseasePhase 1NCT00696566
Healthy Volunteer Study of Clopidogrel and Rifampicin
A Phase 1 study testing Clopidogrel and Rifampicin in people with Coronary Artery Disease, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The principal research question is: Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin? Clopidogrel is an antithrombotic drug in clinical use that reduces the risk of heart attack and coronary stent thrombosis. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Clopidogrel and Rifampicin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2007to Mar 2008
- Phase
- Phase 1
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male subjects, or female subjects not of childbearing potential (either surgically sterile or post menopausal).
- Age between 18 and 65 years inclusive.
- Non smokers.
- Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60 - 100 kg.
- Subjects are to be in good health as determined by a medical history, physical examination including vital signs, and clinical laboratory test results including liver function and full blood count.
- Subjects have given their signed informed consent before any trial-related activity.
Who cannot join
- In the opinion of the investigator, subjects with, or a history of, cancer, diabetes or clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric or other major disorders.
- Subjects with a history of significant multiple drug allergies or with a known allergy to the study drugs or any medicine chemically related to the trial product.
- Subjects who have a clinically significant allergic disease (including hay fever).
- Subjects who have had a clinically significant illness within 4 weeks of dosing.
- Subjects taking regular medication including NSAID's, antibiotics, aspirin or anticoagulant therapy.
- Any clinically significant abnormal laboratory test results at screening.
Show all 13Show fewer
- Subjects who have a supine blood pressure at screening, after resting for 5 min higher than 150/90 mmHg or lower than 100/50 mmHg.
- Subjects who have a supine heart rate at screening, after resting for 5 minutes outside the range of 40 - 90 beats/min.
- Subjects who have received any prescribed systemic or topical medication within two weeks prior to screening (although occasional use of paracetamol is permitted at the discretion of the investigator).
- Subjects who have received an investigational medicinal product within the previous four months (new chemical entity) or three months (licensed product) or subjects who have received a vaccine within three months preceding the start of dosing.
- Subjects who have donated any blood or plasma in the past month or in excess of 500 ml within twelve weeks preceding screening.
- Subjects who have a history of alcohol or drug abuse (consume greater than 28 units per week [one unit of alcohol equals 250 ml of beer or lager or one glass of wine or 20 ml of spirits]).
- Subjects with mental incapacity or language barriers which preclude adequate understanding.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Sheffield Clinical Research Facility, Royal Hallamshire Hospital
Sheffield, S. Yorkshire, S10 2JF
About this study
Official title: Study of the Potentiation of the Effects of Clopidogrel by Rifampicin in Healthy Volunteers
The principal research question is: Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin?
Clopidogrel is an antithrombotic drug in clinical use that reduces the risk of heart attack and coronary stent thrombosis. However some patients respond poorly to clopidogrel, at least partly because they fail to convert it effectively to its active form, and consequently are at higher risk of arterial thrombosis. Preliminary evidence indicates that the antibiotic rifampicin enhances the effectiveness of clopidogrel by increasing its conversion to its active form by the liver. We wish to study further the extent of rifampicin's effect on clopidogrel to see whether this might be useful in clinical practice.
Read the detailed description
Clopidogrel is an antithrombotic drug that is licensed for the treatment and prevention of arterial thrombosis, such as in people admitted to hospital with heart attacks. However, some people fail to achieve a substantial antithrombotic effect from the drug and one important reason for this is that their livers do not convert clopidogrel to its active form effectively. Current evidence suggests that these people are less protected by clopidogrel and have a higher risk of arterial thrombosis than those who respond well to clopidogrel. Rifampicin is an antibiotic that increases the activity of liver enzymes that convert clopidogrel to its active form and preliminary evidence indicates that it increases the effectiveness of clopidogrel. This raises the possibility that rifampicin might be used with clopidogrel to increase its clinical effectiveness. We wish to study this interaction further.
12 healthy volunteers will be recruited for this study after giving informed consent. Following Screening, the study will run over 28 days. Lab safety (clinical chemistry, haematology and urinalysis) will be undertaken on days 7, 22 and 28 in addition to screening. During the first visit, an intravenous cannula will be inserted into a forearm vein. Subjects will perform an erythromycin breath test. Subsequently, venous blood will be obtained via the intravenous cannula and platelet function studies will be performed and a plasma sample will be stored for baseline metabolite analysis. Subsequently the subjects will be administered a 600 mg loading dose of clopidogrel (Plavix, Sanofi Pharma Bristol-Myers Squibb) and further blood samples will be taken over 4 hours for clopidogrel metabolite analysis and platelet function studies. Subjects will then take clopidogrel 75 mg daily for a further 6 days and, 4 hours after the last dose, a further blood sample will be taken using venepuncture for platelet function studies and a plasma sample. After a washout period of 7 days, subjects will then start rifampicin 300 mg twice daily for 14 days (Rifadin, Aventis Pharma). On the 8th day of taking rifampicin, a further intravenous cannula will be inserted, the erythromycin breath test will be repeated, as above, and the same regimen of clopidogrel administration and blood testing will be repeated, this time with co-administration of rifampicin.
The data obtained will allow the following assessments: (i) comparison of the early effects of a 600 mg clopidogrel loading dose and late effects of clopidogrel after 7 days on platelet aggregation and receptor blockade; (ii) assessment of the effects of rifampicin on clopidogrel's action on platelet aggregation and receptor blockade following a loading dose and after prolonged administration of clopidogrel.
- Conditions
- Coronary Artery Disease
- Being tested
- Clopidogrel and Rifampicin
- Keywords
- Thrombosis, Platelet aggregation inhibitor, Blood platelets, P2 receptor, Cytochrome P450
- Medical subject headings
- Coronary Artery Disease, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clopidogrel and RifampicinDrug
Also called Clopidorel = Plavix, Rifampicin = Rifadin
Clopidogrel: loading dose of 600 mg, then 75 mg o.d. for up to 28 days
Rifampicin: 300 mg b.d. for up to 28 days
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | All subjects will receive Clopidogrel and Rifampicin. Receives: Drug: Clopidogrel and Rifampicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin?
Measured: All year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2008 (estimated)
- Study startNov 2007
- Primary completionMar 2008
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies 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 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, University of Sheffield
- Investigators
- Robert F Storey, Principal investigator, University of Sheffield
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00696566
- Sponsor's protocol ID
- STH14468
- Other IDs
- BHF Grant: PG/05/095
- Status last verified
- Jun 2008
- First submitted
- 4 Jun 2008
- Last updated
- 12 Jun 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Potentiation of the Effects of Clopidogrel by Rifampicin in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT00696566
- Acronym / sponsor ID
- STH14468
- Conditions
- Coronary Artery Disease
- Keywords
- Thrombosis, Platelet aggregation inhibitor, Blood platelets, P2 receptor, Cytochrome P450
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- British Heart Foundation, University of Sheffield
- Study start
- Nov 2007
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 12 Jun 2008 (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 principal research question is: Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin?
Clopidogrel is an antithrombotic drug in clinical use that reduces the risk of heart attack and coronary stent thrombosis. However some patients respond poorly to clopidogrel, at least partly because they fail to convert it effectively to its active form, and consequently are at higher risk of arterial thrombosis. Preliminary evidence indicates that the antibiotic rifampicin enhances the effectiveness of clopidogrel by increasing its conversion to its active form by the liver. We wish to study further the extent of rifampicin's effect on clopidogrel to see whether this might be useful in clinical practice.
Detailed description
Clopidogrel is an antithrombotic drug that is licensed for the treatment and prevention of arterial thrombosis, such as in people admitted to hospital with heart attacks. However, some people fail to achieve a substantial antithrombotic effect from the drug and one important reason for this is that their livers do not convert clopidogrel to its active form effectively. Current evidence suggests that these people are less protected by clopidogrel and have a higher risk of arterial thrombosis than those who respond well to clopidogrel. Rifampicin is an antibiotic that increases the activity of liver enzymes that convert clopidogrel to its active form and preliminary evidence indicates that it increases the effectiveness of clopidogrel. This raises the possibility that rifampicin might be used with clopidogrel to increase its clinical effectiveness. We wish to study this interaction further.
12 healthy volunteers will be recruited for this study after giving informed consent. Following Screening, the study will run over 28 days. Lab safety (clinical chemistry, haematology and urinalysis) will be undertaken on days 7, 22 and 28 in addition to screening. During the first visit, an intravenous cannula will be inserted into a forearm vein. Subjects will perform an erythromycin breath test. Subsequently, venous blood will be obtained via the intravenous cannula and platelet function studies will be performed and a plasma sample will be stored for baseline metabolite analysis. Subsequently the subjects will be administered a 600 mg loading dose of clopidogrel (Plavix, Sanofi Pharma Bristol-Myers Squibb) and further blood samples will be taken over 4 hours for clopidogrel metabolite analysis and platelet function studies. Subjects will then take clopidogrel 75 mg daily for a further 6 days and, 4 hours after the last dose, a further blood sample will be taken using venepuncture for platelet function studies and a plasma sample. After a washout period of 7 days, subjects will then start rifampicin 300 mg twice daily for 14 days (Rifadin, Aventis Pharma). On the 8th day of taking rifampicin, a further intravenous cannula will be inserted, the erythromycin breath test will be repeated, as above, and the same regimen of clopidogrel administration and blood testing will be repeated, this time with co-administration of rifampicin.
The data obtained will allow the following assessments: (i) comparison of the early effects of a 600 mg clopidogrel loading dose and late effects of clopidogrel after 7 days on platelet aggregation and receptor blockade; (ii) assessment of the effects of rifampicin on clopidogrel's action on platelet aggregation and receptor blockade following a loading dose and after prolonged administration of clopidogrel.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Clopidogrel and RifampicinAll subjects will receive Clopidogrel and Rifampicin. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy male subjects, or female subjects not of childbearing potential (either surgically sterile or post menopausal).
- Age between 18 and 65 years inclusive.
- Non smokers.
- Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60 - 100 kg.
- Subjects are to be in good health as determined by a medical history, physical examination including vital signs, and clinical laboratory test results including liver function and full blood count.
Key exclusion criteria (13 listed)
- In the opinion of the investigator, subjects with, or a history of, cancer, diabetes or clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric or other major disorders.
- Subjects with a history of significant multiple drug allergies or with a known allergy to the study drugs or any medicine chemically related to the trial product.
- Subjects who have a clinically significant allergic disease (including hay fever).
- Subjects who have had a clinically significant illness within 4 weeks of dosing.
- Subjects taking regular medication including NSAID's, antibiotics, aspirin or anticoagulant therapy.
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 and RifampicinAlso: Clopidorel = Plavix, Rifampicin = RifadinClopidogrel: loading dose of 600 mg, then 75 mg o.d. for up to 28 days Rifampicin: 300 mg b.d. for up to 28 days | Drug | A |
Primary outcome
Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin?
Time frame: All year
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 12 Jun 2008.
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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.
Robert F Storey principal investigator
University of Sheffield
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clopidogrel and Rifampicin in people with Coronary Artery Disease, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
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 6 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: finished, as of the sponsor's last update on 12 Jun 2008. 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 Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin? (time frame: All year). 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 Jun 2008.