Influence of treatment adhesion to clopidogrel on platelet aggregation in subjects carrying coronary stent

ISRCTN	ISRCTN85949729
DOI	https://doi.org/10.1186/ISRCTN85949729
Secondary identifying numbers	N/A

Submission date: 31/08/2010
Registration date: 14/01/2011
Last edited: 15/10/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Michel Burnier
Scientific

Head of the Division of Nephrology and Hypertension
Centre Hospitalier Universitaire Vaudois
Rue du Bugnon 17
Lausanne
1011
Switzerland

Phone	+41 (0)21 314 11 29
Email	michel.burnier@chuv.ch

Study information

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
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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
Study acronym	Eurostar
Study objectives	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(s)	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)
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	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 study start date	01/04/2010
Completion date	01/10/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Total 225 patients: Group 1: n = 90, Group 2 : n = 45, Group 3: n = 90
Total final enrolment	120
Key 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
Key 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
Date of first enrolment	01/04/2010
Date of final enrolment	01/10/2015

Locations

Countries of recruitment

Switzerland

Study participating centre

Head of the Division of Nephrology and Hypertension

Lausanne
1011
Switzerland

Sponsor information

University Hospital Centre and University of Lausanne (CHUV) (Switzerland)
Hospital/treatment centre

Rue du Bugnon 46
Lausanne
1011
Switzerland

Email	michel.burnier@chuv.ch
Website	http://www.chuv.ch/
"ROR"	https://ror.org/05a353079

Funders

Funder type

Government

Swiss Federal Office of Training and Technology (OFFT) (Switzerland) (ref: Eurostar project no. 4776; OFFT contract no: INT.2009.0026)

No information available

EUROSTAR Consortium (a consortium of international partners funds the European project):

No information available

ABR Pharma (France)

No information available

Citobi (Belgium)

No information available

Pharmionic Systems Ltd (Switzerland)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	25/10/2017	15/10/2020	Yes	No

Editorial Notes

15/10/2020: Publication reference and total final enrolment number added.