Contact information
Type
Scientific
Primary contact
Prof Michel Burnier
ORCID ID
Contact details
Head of the Division of Nephrology and Hypertension
Centre Hospitalier Universitaire Vaudois
Rue du Bugnon 17
Lausanne
1011
Switzerland
+41 (0)21 314 11 29
michel.burnier@chuv.ch
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Influence of treatment adhesion to clopidogrel on platelet aggregation in subjects carrying coronary stent: an interventional single centre randomised double-blinded open label trial with three parallel arms
Acronym
Eurostar
Study hypothesis
The analysis of therapeutic adhesion finds a particularly interesting application in the specific case of clopidogrel, an anti-platelet drug, cornerstone in association with aspirin in the treatment of patients undergoing percutaneous coronary interventions. However, the evidence that some patients persist with enhanced platelet reactivity despite treatment with clopidogrel suggest that individual responsiveness to clopidogrel is not uniform and is subject to inter- and intra-individual variability.
Notably, there is a growing degree of evidence that a poor biological response to clopidogrel is associated with the recurrence of cardiovascular ischaemic events. Therefore, the identification of patients "non-responders" constitutes a major therapeutic challenge. To prove lack of efficacy of clopidogrel in a particular patient, we must previously ensure that the drug was administered correctly by answering a key question: Is the patient really a "non-responder" or rather a "non-adherent" to treatment?
The monitoring of treatment adhesion by an electronic control device called MEMS® (Medication Event Monitoring System; AARDEX, Zug, Switzerland) is presently considered the most accurate and sensitive approach to get full information on drug intake. The MEMS® consists in a usual bulk pill container fitted with a special cap, which contains a microelectronic system that automatically records the date and hour of each opening of the bottle.
For therapeutic study purpose, the MEMS® can be utilised in an "usual care" setting (blinding of investigator, physician and patient for adhesion results) or in a classical "integrated care" setting (regular individual drug adhesion results reporting and discussion).
Several methods have been used to assess in vitro clopidogrel-induced anti-platelet effects. Flow cytometric assessment of VASP-P (VASP assay) is a marker of P2Y12 receptor reactivity, thus specific of clopidogrel-induced inhibition. A reduced P2Y12 reactivity ratio is indicative of more enhanced clopidogrel-induced inhibition.
Ethics approval
This study was presented to the Commission cantonale (VD) d'éthique de la recherche sur l'être humain in Switzerland, and approved on the 12th March 2010 (ref: 56/10 EUROSTAR)
Study design
Interventional single centre randomised double-blinded open label trial with three parallel arms
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Coronary stenting
Intervention
Group 1: standard care 6 month follow-up, without electronic pillbox. Total visits: 3.
Group 2: 6 months follow-up with double blinded electronic pillbox (MEMS®), usual care, without feed-back on adherence results. Total visits: 3.
Group 3: 6 months follow up with electronic pillbox (MEMS®), integrated care, with motivational feed-back on adherence results. Total visits: 5.
For each group, a follow-up of the cardiologic events will be made at 12, 24 and 36 months by phone.
Intervention type
Drug
Phase
Not Applicable
Drug names
Clopidogrel
Primary outcome measure
Platelets aggregation (determined by the VASP assay, as index of platelet reactivity) at 6 months
Secondary outcome measures
1. Incidence of cardiovascular events, including: acute non-lethal myocardial infarction, stent thrombosis, cardiovascular mortality
2. Incidence of hemorrhagic complications
3. Drug adherence to clopidogrel using the MEMS® on a 6 months period. The adherence will be measured by 4 parameters: percentage of doses taken, taking adherence, percentage of drug holidays, persistence.
4. Influence of the CYP2C19 polymorphism on aggregation studies in the long term follow-up of patients after coronary stent implantation
Overall trial start date
01/04/2010
Overall trial end date
01/10/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Adult patients greater than 18 years, either sex
2. Treated with clopidogrel (Plavix®) for greater than 6 months after coronary stent implantation (indication: stable/unstable angina or non-invasive functional test positive for myocardial ischaemia ) in the interventional cardiology department
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Total 225 patients: Group 1: n = 90, Group 2 : n = 45, Group 3: n = 90
Participant exclusion criteria
1. Heart failure classification according to New York Heart Association (NYHA) class III or IV
2. ST and non-ST elevation myocardial infarction (less than 1 month)
3. Platelets less than 100,000/l
4. Inflammatory diseases requiring prednisone treatment
5. Medical history of:
5.1. Acute or chronic thrombocytopenia
5.2. Ticlopidine allergy
5.3. Active gastric ulcer (less than 2 months)
5.4. Cerebral hemorrhage (less than 6 months)
5.5. Uncontrolled hypertension greater than or equal to 180/110 mmHg
5.6. Liver Insufficiency CHILD-score greater than or equal to 1
5.7. Bleeding diathesis
5.8. Pregnancy, breast feeding
5.9. Associated drug therapy with CYP2C19 inhibitors
Recruitment start date
01/04/2010
Recruitment end date
01/10/2015
Locations
Countries of recruitment
Switzerland
Trial participating centre
Head of the Division of Nephrology and Hypertension
Lausanne
1011
Switzerland
Sponsor information
Organisation
University Hospital Centre and University of Lausanne (CHUV) (Switzerland)
Sponsor details
Rue du Bugnon 46
Lausanne
1011
Switzerland
michel.burnier@chuv.ch
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Swiss Federal Office of Training and Technology (OFFT) (Switzerland) (ref: Eurostar project no. 4776; OFFT contract no: INT.2009.0026)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
EUROSTAR Consortium (a consortium of international partners funds the European project):
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Location
Funder name
1. ABR Pharma (France)
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2. Citobi (Belgium)
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3. Pharmionic Systems Ltd (Switzerland)
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Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list