Asymptomatic Carotid Surgery Trial -2 (ACST-2). A randomised trial to compare CEA versus CAS to prevent stroke.

Patients with substantial narrowing (stenosis)of the carotid artery, a main
blood supply to the brain, have increased stroke risk. Strokes may occur when
the brain's blood supply is disrupted. A recent trial has shown that surgical
removal of the narrowing (carotid endarterectomy) in patients who have had no
stroke*like symptoms in the previous 6 months (asymptomatic) can substantially
reduce the risk of stroke compared to those who have had medical treatment
alone. Carotid artery stenting (which involves placing a wire mesh to hold the
narrowed part of the artery open) is a new method of treating carotid narrowing
which is rapidly gaining popularity. However, there is very little evidence
that it is safer or even equivalent to treating with carotid surgery. A
multicentre randomised trial comparing carotid stenting with carotid
endarterectomy (CEA) in patients with tight asymptomatic carotid artery
narrowing is therefore needed.

The principal and primary research questions are:
Primary objective: 1) What are the differences in clinical myocardial
infarction (heart attack) rates and in stroke and death within 30 days of
carotid stenting compared with carotid endarterectomy?
Secondary objective: 2) What is the difference in the long*term (5*year)
survival, free of disabling or fatal stroke for carotid stenting versus carotid
endarterectomy?

Secondary outcome measures are:
3) the rate of restenosis in both treatment groups
4) the cost*effectiveness of carotid stenting compared with surgery?

Tertiary outcome measure is:
5) to demonstrate the cerebral white matter state and evaluate the influence of
revascularisation on the occurrence of new cerebral white matter lesions.

Prospective randomised multi center trial. The expected total duration of
participation in the study for each patient is at least 5 years.

Study procedures
As the carotid stenosis is asymptomatic, patients will normally have presented
with other vascular problems. ALL patients with uni* or bilateral carotid
stenosis for whom the collaborating doctor is uncertain whether to treat with
carotid surgery or carotid stenting will be considered. Upon patient consent
all patients will be asked to provide a small amount of blood. This will be
analysed for various e.g. biochemical components in a central laboratory,
appropriately accredited and with the necessary facilities and expertise. Such
analyses would provide direct biochemical information on cardiovascular risk at
the time of joining the study. Analyses will include, for example, profiles of
the different components of blood lipids and the extent of any diabetic
disease. The remaining sample on the paper will be stored and may be used for
further analyses during the study. Information obtained from the sample will
remain strictly confidential and will be used only for the purposes of medical
research. Prior to randomisation, the percentage of stenosis in both carotid
arteries will be estimated using non*invasive duplex ultrasound examination.
Assessment and treatment of risk factors (such as diabetes, hypertension,
hypercholesterolaemia) is extremely important for all patients. Neurological
examination and a MRI-scan of the head and neck region will be undertaken,
according to the pre-operative work-up. This scan is obtained to establish the
narrowing of the carotid artery and baseline white matter state of the brain
before revascularisation. If coronary artery bypass/grafting (or angioplasty)
is needed, this should be done before entering the trial.

Randomisation and treatment:
If a. the carotid artery under consideration is asymptomatic for 6 months or
more, b. the doctor and the patient feel that the patient is fit and willing
EITHER for operation by surgery OR by stenting, and then for follow*up, c. the
patient has given written informed consent to take part in the trial, THEN the
patient will be entered into the trial and randomised either to carotid surgery
or carotid stenting.
Allocated treatment will be carried out as soon as routinely possible. A
procedural follow*up form will be
completed 30 days after the operation or stenting. This will require
neurological re*examination of the patient including non*invasive duplex
ultrasound of both carotids. A major event follow*up form will also be
completed if there have been any strokes, deaths or procedural heart attacks in
the 30 days since the
treatment.

Summary of known and potential risks and benefits.
Myocardial infarction, stroke and death within 30 days of stent or operation.
To minimise these risks,
collaborators carrying out these procedures will have to meet certain criteria
proving their competency before they can join the study. The surgeons will
already have experience in undertaking CEA. The surgeon collaborators will
submit a track record of their results to the ACST*2 office. This will consist
of the results of their previous 25, 50, 100 CEA and/or CAS procedures
(depending on experience). The collaborator*s Track Record of previous stenting
and/or surgery will be assessed prior to entry into the trial. The
collaborators who are then invited to join this trial will be stratified by
experience when analysing the trial outcome data. The collaborator must fall
within the accepted trial guidelines, i.e. <8% stroke and death risk for
symptomatic patients and ~3% risk for asymptomatic patients.

Carotid artery stenting and operation may involve some pain, discomfort,
distress and inconvenience for the
patient, as would any similar procedure. However, in order to take part in the
study, the collaborator and
patient must have already made the decision to carry out a procedure on the
patient for their asymptomatic
carotid narrowing (rather than continuing with medical treatment alone),
despite their risks. The collaborator
should therefore only be 'uncertain' whether to carry out an operation or
stenting to clear the narrowing.
After the procedure, further pain, discomfort, distress and inconvenience to
the patient has been kept to a
minimum. Apart from a neurological follow*up 30 days after the procedure
including a non*invasive duplex
ultrasound, the patient will undergo the standard follow-up protocol of 3
months after revascularisation including a duplex ultrasound. Furthermore the
patient will only be contacted once a year by letter and asked to complete a
simple questionnaire for follow-up information.


Summary of known and potential risks and benefits
There are no direct benefits to be gained by the research participant through
taking part in the research,
except perhaps monitoring over a longer than normal period (yearly
letter/questionnaire for at least 5 years).