Condition category
Circulatory System
Date applied
31/08/2010
Date assigned
14/01/2011
Last edited
14/01/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

http://www.chuv.ch/

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):

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

1. ABR Pharma (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

2. Citobi (Belgium)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

3. Pharmionic Systems Ltd (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes