Intracranial Thrombectomy and Extracranial Carotid Stenting Versus Intracranial Thrombectomy Alone In Acute Anterior Circulation Strokes With TANdem Occlusion : the Randomized Controlled TITAN Trial
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 432
- 试验地点
- 1
- 主要终点
- Change in Modified treatment in cerebral ischemia (mTICI) score AND National Institutes of Health Stroke Scale (NIHSS) score
研究概览
简要总结
Tandem occlusion is defined by an acute ischemic stroke (AIS) with concomitant steno-occlusive disease of the extra cranial carotid artery and concerned about 10% of AIS patients. Whereas endovascular treatment has shown its efficiency in AIS by large vessel occlusion (LVO), to date, there is no consensus on the endovascular management of the extra cranial carotid artery in tandem occlusion. Only few of them were included in previous randomized trials who evaluated mechanical thrombectomy and were often listed in the non-inclusion criteria. Therapeutic management of this population was not specifically addressed in recent trials. Endovascular management can be complex with the need of acute stenting of the extra cranial carotid lesion along with the potential need of antithrombotic therapy initiation, the benefit and the safety of stenting of the cervical lesion in acute phase of AIS have shown encouraging results but however remains to be assessed. The TITAN (Thrombectomy In TANdem lesion) trial aims to demonstrate the superiority of the combined use of intracranial thrombectomy and extracranial carotid stenting compared to intracranial thrombectomy alone on the complete reperfusion rate in patients with acute ischemic stroke due to tandem lesion.
详细描述
The TITAN trial is a prospective, randomized, multi center, controlled, open-label, blinded clinical trial. This academic trial designed to answer the question: "What is the best endovascular management of the extra cranial carotid artery lesion in tandem occlusion with LVO" Patients will be recruited at 13 comprehensive stroke centers in France, all of which regular conduct mechanical thrombectomy and carotid stenting.
This study will enroll adults patients admitted with cerebral infarction of the anterior circulation, proven by computed tomography (CT) or magnetic resonance (MR) angiography, associated with tandem lesion, within 8 hours of symptoms onset, with a neurological deficit NIHSS > 5, and eligible to thrombectomy according to the recommendations of the French societies of neurovascular disease and neuroradiology (SFNR and SFNV).
Tandem occlusion of the anterior circulation will be proven on digital subtraction angiography, defined as a proximal intracranial occlusion and an extracranial severe internal carotid artery (ICA) lesion (complete occlusion or stenosis ≥90% North American Symptomatic Carotid Endarterectomy Trial).
Informed Consent according to the French laws will be sought from the patient if their level of consciousness is sufficient or from a relative. This study will operate using an emergency inclusion protocol due to the nature of the condition.
After emergency inclusion procedure according to French regulations, eligible patients will be randomized in two balanced parallel groups to receive either combined treatment intracranial thrombectomy with carotid stenting or intracranial thrombectomy alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject aged ≥ 18 years
- •Tandem occlusion confirmed by MR angiography or CT-angiography or digital subtraction angiography of supra-aortic vessels, in connection with atheromatous plaque or dissection, defined with:
- •Proximal intracranial occlusion (ICA, M1 and/or M2) eligible for thrombectomy
- •Extracranial lesion of the internal carotid artery (stenosis ≥90% NASCET or complete occlusion).
- •NIHSS Score ≥ 6
- •Arterial puncture performed :
- •> Within 8 hours (after the first symptoms or last seen well) with ASPECTS Score ≥5 by CT or MRI (DWI)
- •> Between 8 and 24 hours :
- •If perfusion imaging performed: according to the DEFUSE3 trial criteria (ischemia ≤70 mL, ischemia-hypoperfusion ratio≥1.8, and hypoperfusion volume ≥15 mL)
- •If perfusion imaging not performed: according to the DAWN trial criteria :
- •Age ≥80 years with NIHSS ≥10 and ischemia ≤21 mL
- •Age <80 years with NIHSS ≥10 and ischemia ≤31 mL
- •Age <80 years with NIHSS ≥20 and ischemia ≤51 mL
- •The patient or his or her representative has received information about the study organization and has signed and dated the informed consent form/ inclusion in emergency situation in accordance with Article L1122-1-3 of the Public Health Code.
- •Person affiliated to or beneficiary of a social security plan
- •Person undergone the medical examination adapted to research Subjects treated with prior intravenous thrombolysis are eligible for participation
排除标准
- •Extracranial internal carotid artery stenosis < 90% (NASCET)
- •Rankin score (mRS) > 2
- •Contraindication to antiplatelet (Aspirin, Plavix), or thrombolytic therapy (Actilyse), or contrast agents, or endovascular products.
- •Patient unable to present or be available for follow-up
- •Patient's refusal to participate
- •Woman of childbearing age without effective contraception
- •Pregnant, parturient or breastfeeding woman
- •Minor person (non emancipated)
- •Adult person under legal protection (any form of public guardianship)
- •Person deprived of liberty for judicial or administrative decision
- •Person under psychiatric care according to articles L. 3212-1 and L. 3213-1 of the Public Health Code.
研究组 & 干预措施
Thrombectomy + Carotid Stenting
Intravenous thrombolysis will be administered if possible. Standard mechanical thrombectomy(MT) will be performed with a balloon Guide Catheter. MT technique will be left at the discretion of the operators.
Concerning the cervical disease, emergent carotid stenting will be performed if the patient is randomized in the intervention arm. The order to treat (head first or neck first), and the choice of a previous angioplasty of the extracranial carotid artery lesion will be left to the interventionist discretion. An intravenous bolus of 250mg of Aspirin (up to Imaging 24H) will be given at the end of the procedure in case of absence of complication.
Intravenous sedation or general anesthesia will be permitted.A second antiplatelet agent is used if a thrombus is formed : IV or nasogastric tube (choice by operator) A dual antiplatelet therapy is administered after 24H imaging follow-up excluding intracranial hemorrhagic complications (discretion of the local practice)
干预措施: Carotid Stenting (Device)
Thrombectomy + Carotid Stenting
Intravenous thrombolysis will be administered if possible. Standard mechanical thrombectomy(MT) will be performed with a balloon Guide Catheter. MT technique will be left at the discretion of the operators.
Concerning the cervical disease, emergent carotid stenting will be performed if the patient is randomized in the intervention arm. The order to treat (head first or neck first), and the choice of a previous angioplasty of the extracranial carotid artery lesion will be left to the interventionist discretion. An intravenous bolus of 250mg of Aspirin (up to Imaging 24H) will be given at the end of the procedure in case of absence of complication.
Intravenous sedation or general anesthesia will be permitted.A second antiplatelet agent is used if a thrombus is formed : IV or nasogastric tube (choice by operator) A dual antiplatelet therapy is administered after 24H imaging follow-up excluding intracranial hemorrhagic complications (discretion of the local practice)
干预措施: Procedural Aspirin (Drug)
Thrombectomy + Carotid Stenting
Intravenous thrombolysis will be administered if possible. Standard mechanical thrombectomy(MT) will be performed with a balloon Guide Catheter. MT technique will be left at the discretion of the operators.
Concerning the cervical disease, emergent carotid stenting will be performed if the patient is randomized in the intervention arm. The order to treat (head first or neck first), and the choice of a previous angioplasty of the extracranial carotid artery lesion will be left to the interventionist discretion. An intravenous bolus of 250mg of Aspirin (up to Imaging 24H) will be given at the end of the procedure in case of absence of complication.
Intravenous sedation or general anesthesia will be permitted.A second antiplatelet agent is used if a thrombus is formed : IV or nasogastric tube (choice by operator) A dual antiplatelet therapy is administered after 24H imaging follow-up excluding intracranial hemorrhagic complications (discretion of the local practice)
干预措施: Dual dual antiplatelet therapy after 24-hours imaging follow-up (Drug)
Thrombectomy + Carotid Stenting
Intravenous thrombolysis will be administered if possible. Standard mechanical thrombectomy(MT) will be performed with a balloon Guide Catheter. MT technique will be left at the discretion of the operators.
Concerning the cervical disease, emergent carotid stenting will be performed if the patient is randomized in the intervention arm. The order to treat (head first or neck first), and the choice of a previous angioplasty of the extracranial carotid artery lesion will be left to the interventionist discretion. An intravenous bolus of 250mg of Aspirin (up to Imaging 24H) will be given at the end of the procedure in case of absence of complication.
Intravenous sedation or general anesthesia will be permitted.A second antiplatelet agent is used if a thrombus is formed : IV or nasogastric tube (choice by operator) A dual antiplatelet therapy is administered after 24H imaging follow-up excluding intracranial hemorrhagic complications (discretion of the local practice)
干预措施: Intracranial thrombectomy (Procedure)
结局指标
主要结局
Change in Modified treatment in cerebral ischemia (mTICI) score AND National Institutes of Health Stroke Scale (NIHSS) score
时间窗: at the end of angiography(mTICI score) , at 24 hours (NIHSS score)
Complete reperfusion rate at the end of angiography defined as a modified Thrombolysis in Cerebral Infarction (mTICI) 3 score and defined as an Improvement of the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 mTICI score : 0:no perfusion ; 1:penetration with minimal perfusion ; 2:partial perfusion ; 2a:partial filling of less than 1/2 of the vascular territory ; 2b:partial filling 50-99% of the vascular territory ; 3:complete perfusion . NIHSS : 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items.
次要结局
- Efficacy outcomes : Number of passes(at the end of the endovascular procedure)
- Efficacy outcomes : Type and dose of antiplatelet agents administered(at 24 (±6) hours, at discharge (5-7 days))
- Efficacy outcomes : Rate of reperfusion with change in Modified treatment in cerebral ischemia (mTICI) score(at the end of the endovascular procedure)
- Efficacy outcomes : Change in National Institutes of Health Stroke Scale (NIHSS) score(at 24 hours (±6) hours)
- Efficacy outcomes : number of participants with delays of symptoms(at the end of the endovascular procedure)
- Efficacy outcomes : Infarct growth (volume)(At 24hours (±6) hours)
- Efficacy outcomes : Rate of recurrent clinical ischemic event(at 90 days for rate of recurrent clinical ischemic event)
- Efficacy outcomes : Rate of functional independence(at 90 days and 12 months for mRS)
- Safety outcomes : Rate of procedural complications(At the end of endovascular procedure)
- Safety outcomes : Rates of carotid stenosis and stent thrombosis(At the end of endovascular procedure)
- Safety outcomes : Rate of symptomatic and asymptomatic intracerebral hemorrhage(at 24 hours (±6 hours))
- Safety outcomes : Rate of carotid stenosis and stent thrombosis(at 24 (±6) hours)
- Safety outcomes :Rate of secondary decompressive craniotomy(at discharge (or 5-7 days))
- Safety outcomes : Rate of endarterectomy(at 90 days and 12 (±1) months)
- Cost effectiveness outcomes : a budget impact analysis(At 12 months)
- Safety outcomes : Rate of mortality(at 24 (±6) hours, 90 (±15) days, and 12 (±1) months)
- Cost effectiveness outcomes : cost of safety issues(At 3 months)
- Cost effectiveness outcomes : a cost-utility analysis(At 12 months)
- Cost effectiveness outcomes : value the additional cost of gaining additional clinical (NIHSS)(At 24 hours)
- Cost effectiveness outcomes : value the additional cost of gaining additional clinical (mRS)(at 3 months)
研究者
Benjamin GORY, MD, PhD
MD, PhD
Central Hospital, Nancy, France