Stroke Prevention With Abciximab in Carotid Endarterectomy
| Status: | Withdrawn |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
In the first portion of the study, the goal will be to determine the safety of the drug
Abciximab for use during and in the period after open carotid artery surgery. In addition,
using specialized ultrasound equipment (a probe that is placed on the outside of your skin
of your head), we will aim to measure the number of particles released around the time of
surgery while being treated with Abciximab. The second phase of the study will be determine
if Abciximab can safely reduce the number of particles released into the bloodstream around
the time of surgery in order to reduce the risk of stroke.
Abciximab for use during and in the period after open carotid artery surgery. In addition,
using specialized ultrasound equipment (a probe that is placed on the outside of your skin
of your head), we will aim to measure the number of particles released around the time of
surgery while being treated with Abciximab. The second phase of the study will be determine
if Abciximab can safely reduce the number of particles released into the bloodstream around
the time of surgery in order to reduce the risk of stroke.
Carotid endarterectomy is the most frequently performed vascular procedure in the United
States. In the last decade, there has been a large increase in case volume following
confirmation of the efficacy of endarterectomy for carotid artery atherosclerotic disease by
the NASCET and ACAS trials. Estimates for 1994 suggested that over 130,000 patients
underwent carotid endarterectomy in the United States.
Despite the efficacy of endarterectomy over medical management for extra cranial cerebral
vascular disease, the risk of having an ipsilateral perioperative stroke after carotid
endarterectomy remains at 2-7%. There are two main types of operation-related stroke. The
intra-operative stroke is apparent upon recovery from anesthesia and is directly
attributable to intra-operative ischemia or embolization. The post-operative stroke occurs
sometime after an uneventful recovery from surgery and is due to vessel occlusion or
embolization off the thrombogenic endarterectomy surface. Evidence suggests that platelets
adhere to the exposed collagen of the endarterectomy surface within minutes of restoring
flow. The maximal rate of adherence appears to be one hour after clamp release.
Postoperative strokes are preceded by micro-particulate embolization, which can be detected
by transcranial Doppler ultrasound. There is good correlation between TCD detection of 25 or
more emboli in the middle cerebral artery distribution during any ten-minute period after
surgery and an increased occurrence of transient ischemic attack and or stroke. Another
study found an embolic rate greater than 50 per hour predicted stroke in 50% of patients.
Further study by TCD of the prevalence of post-operative micro particulate thromboembolic
events after carotid endarterectomy found five percent of patients have sustained
postoperative embolization. The embolic rate is maximal in the first two hours
postoperatively and if no evidence is found for embolization by the third post-operative
hour then it is unlikely to occur thereafter. Infusion of Dextran 40 has been shown to
decrease the rate of embolization of micro particulate debris.
Recent success in decreasing thrombotic events in both percutaneous coronary interventions
and acute myocardial infarction with platelet glycoprotein IIB/IIIA antagonists has
stimulated interest in furthering the applications of these drugs. A recent randomized
clinical trial using Abciximab in acute ischemic stroke documented safety when administered
up to twenty-four hours after stroke onset, with a trend toward improvement in functional
outcomes. Abciximab has also been used in conjunction with heparin and aspirin in carotid
artery percutaneous angioplasty and stenting and is thought to potentially reduce recurrent
stenoses. Unfortunately, the use of platelet IIb/IIIa inhibitors with open surgical
procedures not been studied due to concerns of bleeding.
Study Aims:
Use of a platelet glycoprotein IIb/IIIa antagonist holds great potential for diminishing or
eliminating the micro particulate embolization seen with TCD and thus helping lower the
combined operative morbidity and mortality to less than the five percent rate that is
commonly accepted. Our primary aim is to document the safety and ideal dosing of Abciximab
for use in open vascular surgery, namely Carotid Endarterectomy. Our secondary aim is to
evaluate the incidence of perioperative embolic events after carotid endarterectomy as
monitored by transcranial Doppler with the perioperative administration of Abciximab.
States. In the last decade, there has been a large increase in case volume following
confirmation of the efficacy of endarterectomy for carotid artery atherosclerotic disease by
the NASCET and ACAS trials. Estimates for 1994 suggested that over 130,000 patients
underwent carotid endarterectomy in the United States.
Despite the efficacy of endarterectomy over medical management for extra cranial cerebral
vascular disease, the risk of having an ipsilateral perioperative stroke after carotid
endarterectomy remains at 2-7%. There are two main types of operation-related stroke. The
intra-operative stroke is apparent upon recovery from anesthesia and is directly
attributable to intra-operative ischemia or embolization. The post-operative stroke occurs
sometime after an uneventful recovery from surgery and is due to vessel occlusion or
embolization off the thrombogenic endarterectomy surface. Evidence suggests that platelets
adhere to the exposed collagen of the endarterectomy surface within minutes of restoring
flow. The maximal rate of adherence appears to be one hour after clamp release.
Postoperative strokes are preceded by micro-particulate embolization, which can be detected
by transcranial Doppler ultrasound. There is good correlation between TCD detection of 25 or
more emboli in the middle cerebral artery distribution during any ten-minute period after
surgery and an increased occurrence of transient ischemic attack and or stroke. Another
study found an embolic rate greater than 50 per hour predicted stroke in 50% of patients.
Further study by TCD of the prevalence of post-operative micro particulate thromboembolic
events after carotid endarterectomy found five percent of patients have sustained
postoperative embolization. The embolic rate is maximal in the first two hours
postoperatively and if no evidence is found for embolization by the third post-operative
hour then it is unlikely to occur thereafter. Infusion of Dextran 40 has been shown to
decrease the rate of embolization of micro particulate debris.
Recent success in decreasing thrombotic events in both percutaneous coronary interventions
and acute myocardial infarction with platelet glycoprotein IIB/IIIA antagonists has
stimulated interest in furthering the applications of these drugs. A recent randomized
clinical trial using Abciximab in acute ischemic stroke documented safety when administered
up to twenty-four hours after stroke onset, with a trend toward improvement in functional
outcomes. Abciximab has also been used in conjunction with heparin and aspirin in carotid
artery percutaneous angioplasty and stenting and is thought to potentially reduce recurrent
stenoses. Unfortunately, the use of platelet IIb/IIIa inhibitors with open surgical
procedures not been studied due to concerns of bleeding.
Study Aims:
Use of a platelet glycoprotein IIb/IIIa antagonist holds great potential for diminishing or
eliminating the micro particulate embolization seen with TCD and thus helping lower the
combined operative morbidity and mortality to less than the five percent rate that is
commonly accepted. Our primary aim is to document the safety and ideal dosing of Abciximab
for use in open vascular surgery, namely Carotid Endarterectomy. Our secondary aim is to
evaluate the incidence of perioperative embolic events after carotid endarterectomy as
monitored by transcranial Doppler with the perioperative administration of Abciximab.
Inclusion Criteria:
Subjects will be eligible if the following criteria are met:
- Ability to provide written informed consent and comply with study assessments for the
full duration of the study.
- Age >18 years
- Diagnosis of >75% asymptomatic carotid artery stenosis by ultrasound or angiographic
evaluation
- No contraindication to Abciximab or anticoagulation
- Ability to insonate an adequate window for Transcranial Doppler Imaging
pre-operatively
- In women of childbearing capacity a negative pregnancy test
- Signed authorization of release of protected health care information
Exclusion Criteria:
- Inability to insonate an ipsilateral window; bilateral monitoring will be performed
when possible.
- CT or MRI positive CVA within past 12 weeks
- Active internal bleeding
- Recent within six weeks gastrointestinal or genitourinary bleeding of clinical
significance
- Bleeding diathesis
- Administration of oral anti-coagulants within seven days unless prothrombin time is
less than or equal to 1.2 times control
- History of CVA within two years or CVA with a significant residual neurological
deficit
- Thrombocytopenia (<100,000 cells/uL)
- Recent (within six weeks) major surgery or trauma Intracranial neoplasm, AVM, or
aneurysm
- Severe uncontrolled hypertension
- Presumed or documented history of vasculitis
- Use of intravenous dextran before PCI or intent to use during an intervention
- Known hypersensitivity to any component of ReoPro
- Known hypersensitivity to murine proteins
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