International carotid stenting study: protocol for a randomised clinical trial comparing carotid stenting with endarterectomy in symptomatic carotid artery stenosis

BACKGROUND: Carotid stenting avoids general anaesthesia, cranial nerve injury and the discomforts of surgical treatment of carotid stenosis. A systematic review of the randomised trials showed no overall difference in the major risks of endovascular treatment for carotid stenosis compared with surgery, but the confidence intervals were wide and both methods carried a significant risk of stroke. The use of protection devices appears to improve the safety of endovascular treatment, but there are little randomised data available about long-term outcomes. We have therefore set up an international, multicentre, randomised, controlled, open, prospective clinical trial, namely the International Carotid Stenting Study (ICSS), also known as CAVATAS-2. The objectives of the ICSS are to compare the risks, benefits and cost-effectiveness of a treatment policy of referral for carotid stenting compared with referral for carotid endarterectomy. METHODS: Centres are required to have a team with audited expertise in carotid endarterectomy and stenting procedures, including at least one neurologist or stroke physician, a surgeon and an interventionalist. Attendance at a carotid stenting training course is required. Centres with more limited experience can join the trial as probationary centres, but stenting must then be proctored by an experienced interventionalist. Symptomatic patients are included over the age of 40 years with atherosclerotic carotid stenosis, suitable for both stenting and surgery, and are randomised in equal proportions between carotid endarterectomy and stenting. Stents and other devices are chosen for use at the discretion of the interventionalists but must be approved by the devices committee. The protocol recommends that a cerebral protection system should be used whenever the operator thinks one can be safely deployed. The combination of aspirin and clopidogrel is recommended to cover stenting procedures. Standard or eversion endarterectomy is allowed using local or general anaesthesia, shunts or patches. All patients will receive best medical care. Patients will be followed up by neurologists at 30 days after treatment, 6 months after randomisation and then annually up to 5 years after randomisation. The primary outcome measure is the difference in the long-term rate of fatal or disabling stroke in any territory between patients randomised to stenting or surgery. Secondary outcome measures include any stroke, myocardial infarction or death within 30 days of treatment, treatment- related cranial nerve palsy or haematoma. Restenosis (>70%) on ultrasound follow-up, economic measures and quality of life will also be analysed. The sample size is estimated at 1,500 patients, which will provide 95% confidence intervals of +/- 3.0 percentage points for the outcome measure of 30-day disabling stroke and death rate and +/- 3.3 percentage points for the outcome measure of death or stroke during follow-up. The trial office monitors outcome events at individual centres and a rate of events above a given threshold triggers a blinded assessment of the events, submitted to the chairman of the data-monitoring committee. CONCLUSIONS: The ICSS protocol incorporates a number of novel features to ensure patient safety, including the concept of probationary centres, proctoring of inexperienced investigators and monitoring of individual centre results on an ongoing basis. The protocol is also designed to mirror routine clinical practice as far as possible, so that the results will be widely applicable and relevant to determining the place of carotid stenting in clinical practice in the future.