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.

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.

Treatment and Intervention Intravenous thrombolysis will be administered if possible. Standard MT will be performed with a balloon Guide Catheter (BGC). MT technique (contact aspiration, stent retriever, or solumbra) 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 will be given at the end of the procedure in case of absence of complication. (Aspirin 250mg IV up to Imaging 24H).A second antiplatelet agent is used if a thrombus is formed : IV or nasogastric tube (choice by operator)

Primary objective :

To demonstrate the superiority of intracranial thrombectomy and extracranial carotid stenting compared to intracranial thrombectomy alone on the complete reperfusion (mTICI 3 at the end of the endovascular procedure) rate and on the rate of NIHSS ≥ 4 points improvement at 24 hours in AIS patients with a tandem occlusion of the anterior circulation.

Secondary objectives :

1. To assess the feasibility and the efficacy of the combined approach associating intracranial thrombectomy and extracranial carotid stenting compared to intracranial thrombectomy alone using a composite criterion (mTICI3 at the end of the endovascular procedure or NIHSS improvement ≥ 4 points at 24h).
2. To compare the safety of intracranial thrombectomy and extracranial carotid stenting compared to intracranial thrombectomy alone.
3. To evaluate the cost-effectiveness and cost-utility of the combined approach compared to intracranial thrombectomy alone.

The Data and Safety Monitored Board (DSMB) will provide subject safety oversight and make recommendations to the Sponsor regarding continuing enrollment, modifying, or stopping the study early based upon a review of safety data and more specifically the comparative rates of symptomatic intracranial hemorrhage and, neurological worsening (NIHSS4 points increase), at D1, and mortality rates. They will take into account in their decision making and recommendations the rates of procedure-related and device-related events in the treatment group.

DSMB meetings will be organized by call conference by the sponsor before the start of the study and every year until the end of the study. The members will also receive the results of interim analyses. Additional extraordinary meetings will be set if necessary.

It will be constituted with two independent clinicians and one expert in methodology.

Sample Size Estimates Prior data indicate that a reperfusion rate of 30% mTICI 3 was observed with mechanical thrombectomy in patients with tandem lesions. Assuming acute carotid stenting will bring a 15% gain, a sample size of 162 patients per group will allow to evidence such gain with a 80% power at a 5% type I error (PS v3.0). Allowing 5% loss to follow up leads to include 216 patients per group, i.e. 432 patients in total

Inclusion Criteria:

1. Subject aged ≥ 18 years

2. 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).

3. NIHSS Score ≥ 6

4. Arterial puncture performed :

   -> Within 8 hours (after the first symptoms or last seen well) with ASPECTS Score ≥5 by CT or MRI (DWI)

   OR

   -> 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

5. 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.

6. Person affiliated to or beneficiary of a social security plan

7. Person undergone the medical examination adapted to research Subjects treated with prior intravenous thrombolysis are eligible for participation

Exclusion Criteria:

1. Extracranial internal carotid artery stenosis < 90% (NASCET)
2. Rankin score (mRS) > 2
3. Contraindication to antiplatelet (Aspirin, Plavix), or thrombolytic therapy (Actilyse), or contrast agents, or endovascular products.
4. Patient unable to present or be available for follow-up
5. Patient's refusal to participate
6. Woman of childbearing age without effective contraception
7. Pregnant, parturient or breastfeeding woman
8. Minor person (non emancipated)
9. Adult person under legal protection (any form of public guardianship)
10. Person deprived of liberty for judicial or administrative decision
11. Person under psychiatric care according to articles L. 3212-1 and L. 3213-1 of the Public Health Code.