The role of platelet activation and inflammation in the associated cardiac complications of surgery for peripheral arterial disease: the benefits of additional clopidogrel therapy

ISRCTN	ISRCTN22305120
DOI	https://doi.org/10.1186/ISRCTN22305120
Clinical Trials Information System (CTIS)	2005-000960-25
Protocol serial number	2005/R/CAR/04
Sponsor	Lothian Health Board (LHB) (UK)
Funders	British Heart Foundation (UK) (ref: FS/05/038), European Society of Vascular Surgery (Denmark), Royal College of Surgeons of Edinburgh (UK), Sanofi Aventis (UK) - unrestricted Educational Award

Submission date: 16/06/2008
Registration date: 23/06/2008
Last edited: 16/07/2010

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 David Newby
Scientific

The Chancellors Building
The New Royal Infirmary of Edinburgh
49 Little France Crescent
Edinburgh
EH16 4SU
United Kingdom

Study information

Primary study design	Interventional
Study design	Interventional single-centre, prospective double-blind randomised placebo controlled trial
Secondary study design	Randomised controlled trial
Scientific title	The role of platelet activation and inflammation in the adverse Cardiovascular outcomes of patients undergoing surgery for Critical Limb ISchaemia: a double-blind randomised controlled trial of clopidogrel
Study acronym	CCLIS
Study objectives	We hypothesised that in patients undergoing surgical intervention for critical limb ischaemia: 1. Platelet activation would be increased in patients who subsequently develop a post-operative acute coronary syndrome 2. Additional clopidogrel therapy would reduce markers of systemic inflammation and platelet activation
Ethics approval(s)	Ethics approval received from the Fife and Forth Valley Local resaerch Ethics Committee on the 4th April 2005 (ref: 05/S0501/41; Eudract Number: 2005-000960-25).
Health condition(s) or problem(s) studied	Critical limb ischaemia
Intervention	Pre-operative dual anti-platelet therapy versus single anti-platelet therapy. Patients were maintained on aspirin (75 mg/day) and were randomised to clopidogrel (600 mg prior to surgery, and 75 mg daily for three days) or matched placebo. Total duration of treatment = 4 days (pre-operative loading dose of 600 mg clopidogrel/placebo, plus 75mg/day for 3 days starting on the morning of surgery). Total duration of follow up = 6 months following surgery.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Clopidogrel
Primary outcome measure(s)	Markers of in vivo platelet activation (platelet-monocyte aggregates and platelet expression of P-selectin), measured before study drug, after study drug, post-operatively in the recovery room and between 8 am - 10 am on day one following surgery.
Key secondary outcome measure(s)	1. Markers of myocardial injury (cardiac troponin I [cTn-I]), measured before study drug, after study drug, post-operatively in the recovery room and between 8 am - 10 am on day one following surgery 2. Bleeding outcomes (thrombosis in myocardial infarction [TIMI] and clopidogrel in unstable angina to prevent recurrent events [CURE] classifications); any bleeding events occuring from the time of surgery to hospital discharge 3. Cardiovascular events (acute coronary syndrome, transient ischaemic attack, stroke, death from cardiovascular cause) recorded from time of surgery to hospital discharge, within three months of surgery and within six months of surgery
Completion date	29/02/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	100
Key inclusion criteria	1. Patients aged greater than 45 years, either sex 2. Critical limb ischaemia, defined as the presence of rest pain or skin breakdown, and an ankle-brachial pressure index less than 0.2 3. Scheduled for infra-inguinal bypass, endarterectomy or amputation under general anaesthesia
Key exclusion criteria	1. Women of child bearing potential 2. Non-atherosclerotic vascular disease 3. Sudden acute limb ischaemia requiring emergency surgery 4. Supra-inguinal or aortic surgery 5. History of acute coronary syndrome within three months 6. History of peptic ulcer disease 7. Previous or current intracranial haemorrhage 8. Bleeding diathesis 9. Uncontrolled hypertension or thrombocytopenia 10. Planned epidural or spinal anaesthesia 11. Hypersensitivity or allergy to thienopyridines 12. Current warfarin or thienopyridine use
Date of first enrolment	01/09/2005
Date of final enrolment	29/02/2008

Locations

Countries of recruitment

United Kingdom
Scotland

Study participating centre

The Chancellors Building

Edinburgh
EH16 4SU
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/07/2010		Yes	No