Effect of emergent carotid stenting during endovascular therapy for acute anterior circulation stroke patients with tandem occlusion: A multicenter, randomized, clinical trial (TITAN) protocol

Abstract

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

Mechanical thrombectomy in acute ischemic stroke with tandem occlusions: impact of extracranial carotid lesion etiology on endovascular management and outcome

“…In accordance with other authors, 23,28 a more conservative approach may be considered for dissection in case of good collaterals, especially considering the potential of healing of the dissected ECL over time. While the ongoing TITAN randomized trial 14 and the EASI-TOC 15 will substantially contribute to the knowledge gained by evaluation of the effect of emergency stenting in TOs, further studies are needed to confirm our results.…”

“…5 The Endovascular Acute Stroke Intervention (EASI) trial demonstrated that randomization of patients with TOs is possible, 11 but to date robust data and recommendations about optimal ECL management are lacking. This limited amount of information is reflected in the most recent American 12 and European 13 guidelines, with data from randomized trials on TOs like TITAN (NCT03978988) 14 and the EASI-Tandem Occlusion (EASI-TOC) study, which are still ongoing. 15 The aim of this multicenter study was to explore the impact of the nature of cervical carotid artery lesions, namely CD versus CA, on endovascular management and outcome in patients with AIS and TOs.…”

Expanding indications for endovascular thrombectomy-how to leave no patient behind

“…57 Based on this information a randomized trial by the TITAN collaboration is underway. 58 Based on these preliminary data, we recommend to perform EVT in tandem occlusions with intracranial LVO.…”

Vascular tortuosity in endovascular mechanical thrombectomy

“…[ 23 ] The ongoing thrombectomy in tandem occlusion trial is investigating EVT alone compared to EVT with concomitant extracranial carotid stenting. [ 24 ] Application of this dual procedure theoretically increases the success of EVT; however, thrombectomy with contact aspiration demonstrates comparable revascularization rates and shorter operation times than stenting. [ 25 ] A unique EVT technique employs simultaneous intermediate aspiration and stenting.…”