Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
7907
Study information
Scientific title
An investigation into the effects of cessation of clopidogrel therapy on vascular inflammation and platelet reactivity in patients with drug-eluting coronary stents: is there a "rebound phenomenon"?
Acronym
Study hypothesis
The hypothesis of this trial is that cessation of clopidogrel maintenance therapy after 12 months in patients receiving drug-eluting stents is associated with a pro-inflammatory and pro-thrombotic response that offers an explanation for the observed clustering of clinical events, including stent thrombosis, that have been described in the first 90 days after clopidogrel is stopped.
Antiplatelet agents (drugs used to prevent platelets from binding together and forming blood clots) are widely used in the prevention and treatment of cardiovascular disease. Aspirin and clopidogrel are essential antiplatelet drugs required in all patients undergoing percutaneous coronary intervention (PCI) where narrowed arteries are stretched open with balloons and stents to improve the blood supply to the heart. Previous studies have demonstrated a wide range of patient response to antiplatelet agents. Poor responders are at increased risk of complications including potentially fatal stent thrombosis (blood clot forming within the stent), particularly in the period immediately after cessation of clopidogrel. A large observational study has reported a clustering of events, including death and heart attacks within the first 90days of stopping clopidogrel, raising the possibility of a clopidogrel "rebound" effect. The reason for this effect is unknown and it has been proposed that it may be due to an increase in inflammatory markers and platelet activation following withdrawal of clopidogrel.
The aim of our study is to investigate whether clopidogrel cessation 12 months after PCI causes a rebound proinflammatory and prothrombotic effect. We will investigate the mechanism behind this phenomenon and whether it is related to the lack of synergistic effect of clopidogrel on responses to aspirin when clopidogrel treatment is withdrawn. We will also assess whether the response differs in diabetic patients.
Ethics approval
Southampton and South West Hampshire Research Ethics Committee (A) approved on the 5th November 2009 (ref: 09/H0502/106)
Study design
Randomised interventional screening clinical laboratory study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Cardiovascular; Subtopic: Cardiovascular (all Subtopics); Disease: Cardiovascular
Intervention
Patients are not randomised to any treatment in this trial. All enrolled patients are due to stop dual antiplatelet medication as part of their routine care. This study is assessing the effects of stopping clopidogrel at the end of a routine 12 months course of treatment. Patients are followed up in the study for approximately 7 weeks attending the hospital for 7 blood tests over that time.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
Clopidogrel is routinely used for 12 months after drugeluting stent implantation
Secondary outcome measures
Any differences in inflammatory markers, measured at 12 months
Overall trial start date
01/01/2010
Overall trial end date
01/11/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged greater than 18 years, either sex
2. Signed written informed consent
3. Prior percutaneous coronary intervention (PCI) with drugeluting stent implantation and due to stop clopidogrel 12 months after PCI
4. On maintenance dose aspirin 75 mg and clopidogrel 75 mg daily
5. 30 diabetics and 30 nondiabetics
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 60
Participant exclusion criteria
1. Aged greater than 85 years
2. On regular nonsteroidal antiinflammatory medication or steroids
Recruitment start date
01/01/2010
Recruitment end date
01/11/2010
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
Sponsor information
Organisation
Southampton University Hospitals NHS Trust (UK)
Sponsor details
MRC Environmental Epidemiology Unit
Tremona Road
Southampton
SO16 6YD
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Haemonetics Limited (UK)
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
Basic results (scientific)
Publication list
2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21795297
Publication citations
-
Results
Sambu N, Dent H, Englyst N, Warner TD, Leadbeater P, Roderick P, Gray H, Simpson I, Corbett S, Calver A, Morgan J, Curzen N, Effect of clopidogrel withdrawal on platelet reactivity and vascular inflammatory biomarkers 1 year after drug-eluting stent implantation: results of the prospective, single-centre CESSATION study., Heart, 2011, 97, 20, 1661-1667, doi: 10.1136/heartjnl-2011-300192.