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Rationale: Mechanical thrombectomy (MT) associated with the best medical treatment (BMT) has recently shown efficacy for the management of acute ischemic stroke (AIS) secondary to a large vessel occlusion. However, evidence is lacking regarding the benefit of MT for more distal occlusions., Aim: To evaluate the efficacy in terms of good clinical outcome at 3 months of MT associated with the BMT over the BMT alone in AIS related to a distal occlusion., Methods: The DISCOUNT trial is a multicenter open-label randomized controlled trial involving French University hospitals. Adult patients (⩾18 years) with an AIS involving the anterior or posterior circulation secondary to a distal vessel occlusion within 6 h of symptom onset or within 24 h if no hyperintense signal on fluid attenuation inversion recovery acquisition will be randomized 1:1 to receive either MT associated with the BMT (experimental group) or BMT alone (control group). The number of patients to be included is 488., Study Outcomes: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin scale (mRS) ⩽2 and evaluated by an independent assessor blinded to the intervention arm. Secondary outcomes include recanalization of the occluded vessel within 48 h, angiographic reperfusion in the experimental group, 3-month excellent clinical outcome (mRS ⩽ 1), all adverse events, and death. A cost utility analysis will estimate the incremental cost per quality-adjusted life year (QALY) gained., Discussion: If positive, this study will open new insights in the management of AISs., Trial Registration: ClinicalTrials.gov: NCT05030142 registered on 1 September 2021., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B.G. has received grants from the French Ministry of Health and is the primary investigator of the TITAN, DIRECT ANGIO, and IA-RESCUE trial, and consulting fees from Boerhinger Ingelheim, Air Liquide, MIVI, Medtronic, Microvention, and Penumbra. A.S. reports conflicts of interest with Medtronic, Balt Extrusion, and Microvention (consultant). F.C. reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board). J.-C.G. reports conflicts of interest with Stryker (consultant), Medtronic (consultant), Microvention (consultant), Balt, and Intradys (consultant). I.D.-Z. reports a conflict of interest with Medtronic (honoraria for research, lecturing and acting as an advisor). G.T. reports a conflict of interest with Guerbet France (Lecturing fees). N.B. reports a conflict of interest with Stryker and QApel (consultant). I.S. reports a conflict of interest with Sanofi Synthé-Labo, Servier, Boheringer Ingelheim, Astra-Zeneca, Novonordisk, Medtronic (consultant), and BMS-Pfizer (Lecturing fees). Prof. Cognard reports a conflict of interest with Medtronic, Stryker, Microvention, Cerenovus, and MIVI (consultant). S.A. reports a conflict of interest with Boehringer Ingelheim, Astra-Zeneca, Pfizer, and Amgen (participation in advisory meetings and satellite symposia). S.A. is also the principal investigator of the Tenecteplase treatment in Ischemic Stroke (TETRIS) registry (financial support from Boehringer Ingelheim) and of the ToGiac trial (supported by a research grant from Roche-Shugai). S.R. reports conflict of interest with Boheringer Ingelheim, Bristol-Myers Squibb (scientific expertise), and Acticor (study coordination).

Background and Hypothesis: There is no consensus on the optimal endovascular management of the extracranial internal carotid artery steno-occlusive lesion in patients with acute ischemic stroke due to tandem occlusion. We hypothesized that intracranial mechanical thrombectomy plus emergent internal carotid artery stenting (and at least one antiplatelet therapy) is superior to intracranial mechanical thrombectomy alone in patients with acute tandem occlusion., Study Design: TITAN is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study. Eligibility requires a diagnosis of acute ischemic stroke, pre-stroke modified Rankin Scale (mRS)≤2 (no upper age limit), National Institutes of Health Stroke Scale (NIHSS)≥6, Alberta Stroke Program Early Computed Tomography Score (ASPECTS)≥6, and tandem occlusion on the initial catheter angiogram. Tandem occlusion is defined as large vessel occlusion (intracranial internal carotid artery , M1 and/or M2 segment) and extracranial severe internal carotid artery stenosis ≥90% (NASCET) or complete occlusion. Patients are randomized in two balanced parallel groups (1:1) to receive either intracranial mechanical thrombectomy plus internal carotid artery stenting (and at least one antiplatelet therapy) or intracranial mechanical thrombectomy alone within 8 h of stroke onset. Up to 432 patients are randomized after tandem occlusion confirmation on angiogram., Study Outcomes: The primary outcome measure is complete reperfusion rate at the end of endovascular procedure, assessed as a modified Thrombolysis in Cerebral Infarction (mTICI) 3, and ≥4 point decrease in NIHSS at 24 h. Secondary outcomes include infarct growth, recurrent clinical ischemic event in the ipsilateral carotid territory, type and dose of antiplatelet therapy used, mRS at 90 (±15) days and 12 (±1) months. Safety outcomes are procedural complications, stent patency, intracerebral hemorrhage, and death. Economics analysis includes health-related quality of life, and costs utility comparison, especially with the need or not of endarterectomy., Discussion: TITAN is the first randomized trial directly comparing two types of treatment in patients with acute ischemic stroke due to anterior circulation tandem occlusion, and especially assessing the safety and efficacy of emergent internal carotid artery stenting associated with at least one antiplatelet therapy in the acute phase of stroke reperfusion., Trial Registration: ClinicalTrials.gov NCT03978988.