Status:
Trial completed recruitment in February 2006, with 1,214 patients randomized. 30-day outcome results were published in October 2006. Two-year follow-up results were published in late 2008.
Purpose:
To compare the safety and prophylactic efficacies of stent-protected percutaneous angioplasty of the carotid artery (SPAC) and carotid endarterectomy (CEA) against stroke and other vascular events in patients with symptomatic carotid stenosis.
Location(s):
Germany, Austria, Switzerland.
Year Started:
2001
Year Finished:
2006
Year Presented:
2009
Design:
Prospective, randomized, independently-controlled, multi-center trial.
Inclusion Criteria
Patients with severe carotid stenosis (>= 70% by Duplex sonography, >= 50% by NASCET criteria, or >= 70% by ECST criteria ) who have experienced amaurosis fugax, transient ischemic attack (TIA), prolonged reversible ischemic neurological deficit (PRIND), or other mild stroke within 180 days of randomization, and who have a modified Rankin scale (MRS) score =< 3, will be eligible for this trial.
TIA, amaurosis fugax, or non-disabling stroke (mod. Rankin <= 3) occurring within 180 days in patients
Exclusion Criteria
Pregnant females, and persons with a history of intracranial bleeding within 90 days of randomization, who have a confirmed arteriovenous malformation or aneurysm, who have a serious comorbid illness limiting life expectancy to less than 2 years, who have an uncontrolled coagulopathy, who have any contraindication for heparin, ASA, clopidogrel, or contrast media, who have stenosis or dissection of the common and/or internal carotid arteries, who have stenosis following surgical or endovascular pretreatment, whose stenoses result from radiation therapy, fibromuscular dysplasia, or endovascular thrombosis, who have tandem stenoses (if the distal stenosis is the more severe), who have other planned surgical interventions, or who have any comorbid condition that, in the opinion of the investigator, would interfere with the study, will be excluded from this trial.
Patient Involvement:
Prior to enrollment, all patients will undergo Duplex sonography. Eligible patients will be randomized to receive either SPAC or CEA. If patients have bilateral stenosis, they will be randomized to receive treatment on the side associated with their most recent symptoms. Prior to their surgeries, all patients will receive either aspirin 50 - 325 mg/day or Clopidogrel 75 mg/day, as well as enoxaparin sodium 100 IE/kg/day or another low-molecular-weight heparin in the same dosage. All patients must be surgically treated within 14 days of randomization. Following treatment, patients will receive either aspirin 50-325 mg/day, clopidogrel 75 mg/day, or ticlopidine 500 mg/day, and, if necessary, phenprocoumon dosed to achieve an international normalized ratio (INR) of 2 - 3. Patients will be followed-up by study clinicians at 6 days, 1, 6, 12, and 24 months post-treatment. At each follow-up visit, patients will be evaluated for the occurrence of all endpoints, and for clinical impairment, measured by the National Institute of Health Stroke Scale (NIHSS) and the MRS. An interim analysis will be performed after 2 years have passed or 900 patients have been treated, whichever happens first.
Primary Outcome:
30-day incidence of ipsilateral cerebrovascular events (cerebral infarction and/or hemorrhage with symptoms lasting for more than 24 hours); 30-day mortality.
Secondary Outcome:
24-month incidence of death or ipsilateral stroke; frequency of high-grade restenosis (>=70% by Duplex sonography) of the treated artery at 6, 12, and 24 months; number of technical complications (MI, vascular occlusion, residual stenosis >= 70%) at 6 and 30 days; stroke in either hemisphere at 30 days and 24 months post-treatment.
Results:
1 214 patients were randomly assigned (613 were randomly assigned to carotid angioplasty with stenting and 601 were randomly assigned to carotid endarterectomy). In both the intention-to-treat and per-protocol analyses the Kaplan-Meier estimates of ipsilateral ischaemic strokes up to 2 years after the procedure and any periprocedural stroke or death do not differ between the carotid artery stenting and the carotid endarterectomy groups (intention to treat 9.5%vs 8.8%; hazard ratio (HR) 1.10, 95%CI 0.75 to 1.61; log-rank p=0.62; per protocol 9.4%vs 7.8%; HR 1.23, 95%CI 0.82 to 1.83; log-rank p=0.31). In both the intention-to-treat and per-protocol populations, recurrent stenosis of 70% or more is significantly more frequent in the carotid artery stenting group compared with the carotid endarterectomy group, with a life-table estimate of 10.7% versus 4.6% (p=0.0009) and 11.1% versus 4.6% (p=0.0007), respectively. Only two incidences of recurrent stenoses after carotid artery stenting led to neurological symptoms. After 2 years' follow-up, the rate of recurrent ipsilateral ischaemic strokes reported in the SPACE trial is similar for both treatment groups. The incidence of recurrent carotid stenosis at 2 years, as defined by ultrasound, is significantly higher after carotid artery stenting. However, it cannot be excluded that the degree of in-stent stenosis is slightly overestimated by conventional ultrasound criteria.
Source of Information:
Information from Principal Investigators 2/01.
Stroke. 2002;33:646.
Presented at 30th International Stroke Conference [February 2005].
Presented at the 2006 International Stroke Conference [February 2006].
Correspondence with principal investigator 9/22/06.
Presented at the 2009 International Stroke Conference [February 2009].
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