Additional identifiers
EudraCT number
2005-000960-25
ClinicalTrials.gov number
Protocol/serial number
2005/R/CAR/04
Study information
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
Acronym
CCLIS
Study hypothesis
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
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).
Study design
Interventional single-centre, prospective double-blind randomised placebo controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
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 names
Clopidogrel
Primary outcome measure
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.
Secondary outcome measures
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
Overall trial start date
01/09/2005
Overall trial end date
29/02/2008
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
Participant 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
Recruitment start date
01/09/2005
Recruitment end date
29/02/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
The Chancellors Building
Edinburgh
EH16 4SU
United Kingdom
Sponsor information
Organisation
Lothian Health Board (LHB) (UK)
Sponsor details
c/o Heather Cubie
49 Little France Crescent
Edinburgh
EH16 4SU
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Research organisation
Funder name
British Heart Foundation (UK) (ref: FS/05/038)
Alternative name(s)
BHF
Funding Body Type
private sector organisation
Funding Body Subtype
Trusts, charities, foundations (both publically funded and privately funded)
Location
United Kingdom
Funder name
European Society of Vascular Surgery (Denmark)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Royal College of Surgeons of Edinburgh (UK)
Alternative name(s)
RCSEd
Funding Body Type
private sector organisation
Funding Body Subtype
professional associations and societies
Location
United Kingdom
Funder name
Sanofi Aventis (UK) - unrestricted Educational Award
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
2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20562608
Publication citations
-
Results
Burdess A, Nimmo AF, Garden OJ, Murie JA, Dawson AR, Fox KA, Newby DE, Randomized controlled trial of dual antiplatelet therapy in patients undergoing surgery for critical limb ischemia., Ann. Surg., 2010, 252, 1, 37-42, doi: 10.1097/SLA.0b013e3181e40dde.