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
EudraCT/CTIS number	2005-000960-25
Secondary identifying numbers	2005/R/CAR/04

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

Study design	Interventional single-centre, prospective double-blind randomised placebo controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
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
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	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 study start date	01/09/2005
Completion date	29/02/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	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

Scotland
United Kingdom

Study participating centre

The Chancellors Building

Edinburgh
EH16 4SU
United Kingdom

Sponsor information

Lothian Health Board (LHB) (UK)
Hospital/treatment centre

c/o Heather Cubie
49 Little France Crescent
Edinburgh
EH16 4SU
Scotland
United Kingdom

Website	http://www.research.luht.scot.nhs.uk/home.htm
"ROR"	https://ror.org/03q82t418

Funders

Funder type

Research organisation

British Heart Foundation (UK) (ref: FS/05/038)
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): the_bhf, The British Heart Foundation, BHF
Location: United Kingdom

European Society of Vascular Surgery (Denmark)

No information available

Royal College of Surgeons of Edinburgh (UK)
Private sector organisation / Associations and societies (private and public)

Alternative name(s): RCSEd
Location: United Kingdom

Sanofi Aventis (UK) - unrestricted Educational Award

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	01/07/2010		Yes	No