Abciximab for Prevention of Stroke Recurrence Before Endarterectomy in Symptomatic Carotid Stenosis
|First Received Date ICMJE||July 29, 2005|
|Last Updated Date||May 1, 2007|
|Start Date ICMJE||April 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Whether abciximab compared with aspirin reduces the rate of recurrent ischemic strokes in territory of symptomatic carotid artery during administration of study drug, preoperative period or carotid endarterectomy|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00126139 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Abciximab for Prevention of Stroke Recurrence Before Endarterectomy in Symptomatic Carotid Stenosis|
|Official Title ICMJE||Abciximab Versus Aspirin for Prevention of Stroke Recurrence Before Endarterectomy in Symptomatic >50% Carotid Stenosis: A Pilot Study (ASTERICS)|
The purpose of the present prospective, randomized, double-blind, double dummy controlled multicenter pilot study is to investigate whether abciximab, compared with aspirin, is able to reduce the rate of recurrent ischemic strokes before and during carotid endarterectomy [CEA] (primary endpoints); and the degree of carotid stenosis, number of microembolic signal (MES) counts, number of ischemic infarcts at diffusion weighted imaging (DWI) and amount of intraluminal thrombus at pathological examination (secondary endpoints) in patients with ischemic stroke due to a >50% carotid stenosis who will undergo CEA.
Prospective randomized trials have shown that carotid endarterectomy (CEA) is beneficial for stroke prevention in symptomatic severe or moderate stenoses of the carotid artery. Medical treatment and timing of CEA after a recent stroke due to carotid narrowing, however, remain controversial. Prospective, placebo-controlled acute stroke trials did either not screen for or excluded carotid stenoses. The early experience with CEA resulted in a generally accepted policy to delay surgery for 4 to 6 weeks for fear of clinical deterioration associated with conversion of a bland to a hemorrhagic infarction. Subsequent studies suggest that endarterectomy need not necessarily be postponed in patients with nondisabling strokes, which was not confirmed by Giordano. Furthermore, not all patients recover fast enough to allow early carotid surgery for a nondisabling stroke. The risk of a recurrent stroke while waiting 4 to 6 weeks for CEA was 9.5% in 74 prospectively studied patients and 21% in a retrospective series of 19 patients. Similarly, 4.9% of the 103 medically treated patients with stroke and severe carotid stenosis had recurrent ipsilateral strokes within 30 days after entry in the NASCET trial. Analogous to coronary artery disease, carotid stenoses are assumed to become symptomatic from plaque fissure leading to exposure of its contents to the blood, platelet activation and thrombosis that may cause cerebral or ocular emboli and further narrows the vessel lumen. Therefore, the administration of a drug, which reduces the amount of carotid thrombosis and thus stabilizes the plaque would be expected to reduce the risk of recurrent stroke and progression of carotid stenosis to occlusion, and allow to postpone CEA. Furthermore, also intraoperative ischemic strokes due to cerebral emboli arising from a friable plaque during dissection and cross-clamping of the carotid artery may decrease.
Prospective percutaneous coronary revascularization trials using balloon angioplasty, stenting and atherectomy in patients with ischemic heart disease have shown that the addition of abciximab, a blocker of platelet glycoprotein (GP) IIb/IIIa receptors, during intervention reduced the rates of thrombotic complications, particularly myocardial infarction, and death within 30 days. Symptomatic intracranial hemorrhage (ICH) occurred in 0.0-0.1% of 2535 patients treated with abciximab, medium-dose aspirin, low-dose heparin and endovascular procedures. Endovascular coronary interventions disrupt or dissect the arterial wall, which leads to exposure of plaque contents and components of the vascular wall to the blood, resulting in platelet activation and thrombosis. Interestingly, also abciximab given 18 to 24 hours prior to intervention reduced the rate of thrombotic events suggesting some stabilization of the coronary plaque.
A recent prospective, placebo-controlled safety and pilot efficacy trial of abciximab in 74 patients with acute ischemic stroke treated within 24 hours from symptoms onset found that abciximab caused no symptomatic ICH and showed a trend toward a higher rate of patients with minimal residual disability. Thus, abciximab may be an attractive therapy option to prevent stroke recurrence in patients with embolic carotid territory stroke due to carotid stenosis.
The number of microembolic signals (MES) detected in the middle cerebral artery (MCA) downstream to a symptomatic carotid stenosis by transcranial Doppler sonography (TCD) has been shown to predict the stroke risk, and is dramatically reduced in patients with acute ischemic stroke not caused by carotid artery disease during the administration of the GP IIb/IIIa inhibitor tirofiban. These data suggest that the monitoring of MES in the MCA distal to a symptomatic carotid stenosis before and after the administration of abciximab may be a useful surrogate marker to assess the efficacy of this drug to prevent MES and stroke in patients with symptomatic carotid stenosis. Diffusion-weighted MR imaging (DWI) has a high sensitivity for detecting acute brain ischemia, and recent DWI studies have assessed the incidence of asymptomatic ischemic brain lesions in patients who underwent CEA.
The purpose of the present prospective, randomized, double-blind, double dummy controlled multicenter pilot study is to investigate whether abciximab compared with aspirin is able to reduce the rate of recurrent ischemic strokes before and during CEA (primary endpoints), and the degree of carotid stenosis, number of MES counts, number of ischemic infarcts at DWI and amount of intraluminal thrombus at pathological examination (secondary endpoints) in patients with ischemic stroke due to a >50% carotid stenosis who will undergo CEA.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Abciximab|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Terminated|
|Completion Date||May 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Switzerland|
|NCT Number ICMJE||NCT00126139|
|Other Study ID Numbers ICMJE||E-046/2001|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||University of Zurich|
|Information Provided By||University of Zurich|
|Verification Date||May 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP