Risk Reduction of Symptomatic and Silent Brain Infarctions During Carotid Endarterectomy by the Ultrasound Activation of Endogenous Fibrinolytic System Using Sonolysis (Transcranial Doppler Monitoring)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 1,492
- 试验地点
- 1
- 主要终点
- Occurence of ischemic stroke, transient ischemic attack and death within 30 days
研究概览
简要总结
SONOBIRDIE Trial is a randomized, single-blind, sham-controlled study designed for a demonstration of the safety and effectiveness of sonolysis (continual transcranial Doppler (TCD) monitoring) in reduction of risk of stroke or transient ischemic attack (TIA), brain infarctions and cognitive decline using a 2-MHz diagnostic probe with a maximal diagnostic energy on the reduction of risk of brain infarctions by the activation of endogenous fibrinolytic system during carotid endarterectomy (CEA) in patients with ≥ 70% symptomatic or asymptomatic internal carotid artery stenosis.
The sample size is based on an expected 2.5% reduction of ischemic stroke, TIA, and death during the 30-day postoperative period in the sonolysis group (estimated prevalence, 1.5 %) compared to the control group (estimated prevalence, 4 %). Pre-study calculations showed that a minimum of 746 patients in each group is needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 10 % would be lost to follow-up or refuse to participate in the study.
Consecutive patients will be assigned to the sonolysis or control group by a computer-generated 1:1 randomization. In patients randomized into sonolysis group, middle cerebral artery segment in a depth of 55 mm will be continuously monitored during intervention using a diagnostic 2-MHz TCD probe with a maximal diagnostic energy.
In patients randomized into control group, the TCD probe will be fixed in a required position using a special helmet as in sonolysis group patients, but middle cerebral artery segment in a depth of 55 mm will be only localized using a diagnostic 2-MHz TCD probe with a maximal diagnostic energy and the TCD monitoring will be stopped afterwards.
Confirmation of the investigators hypothesis that sonothrombolysis is able to activate endogenous fibrinolytic system during CEA with consecutive reduction of ischemic stroke, TIA or death, and the number and volume of brain infarcts, can lead to the increase of the safety of CEA in patients with internal carotid artery stenosis. The investigators can presume that up to 50% of patients indicated for CEA can be treated using these methods in the future.
详细描述
Results of the NASCET, ECST and ACAS studies showed that carotid endarterectomy (CEA) was a beneficial therapy for patients with a symptomatic internal carotid artery (ICA) stenosis >50% and asymptomatic ICA stenosis >60%, resp. Surgical risk of CEA varied between 2 and 15 % and even clinically silent microembolism can cause microinfarctions presenting with postoperative cognitive deficit.
Transcranial Doppler (TCD) monitoring during CEA is a common diagnostic method being used for the detection of microemboli and changes of blood flow in intracranial arteries. Reduction of periprocedural complications of CEA with TCD monitoring referred in some studies should be not only due to sophisticated indication of shunt implementation, optimization of surgery and anesthesia but also due to TCD activation of endogenous fibrinolytic system (equal to sonothrombolysis in acute stroke studies). Recently published SONOBUSTER Trial showed that intraoperative sonolysis reduced both the incidence and the volume of new brain infarctions following CEA.
There are 2 possible effects of ultrasound on thrombus - mechanical destruction due to vibration of thrombus with acceleration of penetration of fibrinolytics into thrombus and elevation of temperature and stimulation of endothelium with local activation of fibrinolytic system. Grant project NR/9487-3/2007 showed that TCD monitoring has a significant effect on activation of fibrinolytic system in healthy volunteers.
STUDY OBJECTIVES The objective of the randomized, double-blind, sham-controlled study is to demonstrate the safety and effectiveness of sonolysis (continual TCD monitoring) using a 2-MHz diagnostic probe with a maximal diagnostic energy on the reduction of stroke, transient ischemic attack (TIA) and brain infarction by the activation of endogenous fibrinolytic system during CEA in patients with ≥70% symptomatic or asymptomatic ICA stenosis.
The substudy aims to compare the risk of brain infarction detected using magnetic resonance between sonolysis and control group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has a symptomatic or asymptomatic ICA stenosis ≥ 70 % (NASCET criteria) as detected by a duplex sonography (see Appendix) and confirmed using the computed tomography angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA).
- •Subject is indicated for CEA according to the criteria set by the American Heart Association.
- •Subject is aged 40 - 85 years.
- •Subject has a sufficient temporal bone window for TCD with detectable blood flow in the MCA.
- •Subject is functionally independent with a modified Rankin score value of 0 - 2 points.
- •Informed consent is signed by the subject.
排除标准
- •Subject has been participating in another clinical trial within last 6 weeks.
- •Subject has any other medical condition that would make him/her inappropriate for study participation, in the Investigator opinion.
研究组 & 干预措施
Sonolysis
In patients randomized into sonolysis group, middle cerebral artery segment in a depth of 55 mm will be continuously monitored during intervention using a diagnostic 2-MHz transcranial Doppler probe with a maximal diagnostic energy. The probe will be fixed in a required position using a special helmet and sonolysis will start before the carotid intervention and will be stopped after the intervention, but at latest after 120 minutes. Transcranial Doppler machine with a 2-MHz diagnostic transcranial Doppler probe will be used. This non-diagnostic transcranial Doppler monitoring will be performed without detection of microembolic signals or detection of changes in blood flow. Device sound and Doppler wave imaging will be switched off. Only sonographer will be unblinded to the procedure.
干预措施: sonolysis (Device)
Shame sonolysis
In patients randomized into control group, the transcranial Doppler probe will be fixed in a required position using a special helmet as in sonolysis group patients, but middle cerebral artery segment in a depth of 55 mm will be only localized using a diagnostic 2-MHz transcranial Doppler probe with a maximal diagnostic energy and the transcranial Doppler monitoring will be stopped afterwards. Patients in the control group will undergo a sham procedure in which further sonolysis (transcranial Doppler monitoring) will not be conducted.
干预措施: sonolysis (Device)
结局指标
主要结局
Occurence of ischemic stroke, transient ischemic attack and death within 30 days
时间窗: 30 days after randomization
The incidence of ischemic stroke, transient ischemic attack and death within 30 days in sonolysis and control groups
次要结局
- Postprocedural changes in cognitive functions(24 hours after intervention)
- Occurence of new ipsilateral ischemic lesion on post-procedural brain DWI-MRI (Substudy)(24 hours after intervention)
- Occurence of hemorrhagic stroke(30 days after randomization)
- Occurence of intracranial bleeding (including brain microbleeds) on control T2*-MR (substudy)(24 hours after intervention)
- Occurrence of death within 1 year(30 year after randomization)
- Occurence of new ischemic lesion ≥0.5 mL on post-procedural brain DWI-MRI (Substudy)(24 hours after intervention)
- Occurrence of myocardial infarction within 30 days(30 days after randomization)
- Changes in cognitive functions within 1 year(1 year after randomization)
- Changes in cognitive functions within 30 days(30 days after randomization)
- Occurrence of death within 30 days(30 days after randomization)
- Occurrence of any stroke within 30 days(30 days after randomization)
- Occurence of new ischemic lesion on post-procedural brain DWI-MRI (Substudy)(24 hours after intervention)
- Number of new ischemic lesions on brain DWI-MRI (Substudy)(24 hours after intervention)