Condition category
Circulatory System
Date applied
23/04/2010
Date assigned
23/04/2010
Last edited
22/07/2013
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

Dr Nicholas Curzen

ORCID ID

Contact details

Southampton General Hospital
Cardiology Research
Wessex Cardiac Unit
Mail Point 46
Southampton
SO16 6YD
United Kingdom

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 measures

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

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

http://www.suht.nhs.uk/home.aspx

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

Results - basic reporting

Publication summary

2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21795297

Publication citations

  1. 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.

Additional files

Editorial Notes