Stroke Clinical Trial
— TITANOfficial title:
Intracranial Thrombectomy and Extracranial Carotid Stenting Versus Intracranial Thrombectomy Alone In Acute Anterior Circulation Strokes With TANdem Occlusion : the Randomized Controlled TITAN Trial
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.
Status | Recruiting |
Enrollment | 432 |
Est. completion date | October 30, 2025 |
Est. primary completion date | October 30, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
France | CHRU de Nancy | Vandoeuvre les Nancy |
Lead Sponsor | Collaborator |
---|---|
Central Hospital, Nancy, France |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in Modified treatment in cerebral ischemia (mTICI) score AND National Institutes of Health Stroke Scale (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. |
at the end of angiography(mTICI score) , at 24 hours (NIHSS score) | |
Secondary | Efficacy outcomes : Rate of reperfusion with change in Modified treatment in cerebral ischemia (mTICI) score | Complete reperfusion rate at the end of angiography defined as a modified Thrombolysis in Cerebral Infarction (mTICI) 3 score.
mTICI score (0,1,2,2a,2b,3) : Grade 0 : no perfusion Grade 1 : penetration with minimal perfusion Grade 2 : partial perfusion Grade 2a : partial filling of less than 1/2 of the vascular territory Grade 2b : partial filling 50-99% of the vascular territory Grade 3 : complete perfusion |
at the end of the endovascular procedure | |
Secondary | Efficacy outcomes : Change in National Institutes of Health Stroke Scale (NIHSS) score | NIHSS improvement = 4 points at 24 (±6) hours (blinded assessment : core laboratories of 2 independent neuroradiologists).
National Institutes of Health Stroke Scale (NIHSS) score. The NIHSS is a 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. The single patient assessment requires less than 10 minutes to complete. The evaluation of stroke severity depends upon the ability of the observer to accurately and consistently assess the patient. |
at 24 hours (±6) hours | |
Secondary | Efficacy outcomes : number of participants with delays of symptoms | - Delays of symptoms onset to groin puncture, groin puncture to clot contact, groin puncture to reperfusion, and symptoms onset to reperfusion | at the end of the endovascular procedure | |
Secondary | Efficacy outcomes : Number of passes | Number of intracranial thrombectomy passes to achieve final reperfusion | at the end of the endovascular procedure | |
Secondary | Efficacy outcomes : Infarct growth (volume) | Infarct growth difference between treatment and control groups expressed as difference in Alberta Stroke Program Early CT score (ASPECT scores) at 24 (±6) hours.
ASPECT scores : A 10-point score to assess ischemic stroke in the territory of the middle cerebral artery on a brain scan without injection. Calculated on a CT without axial cross-sectional injection: No hypodensity = 1 point Score = 10: total absence of hypodensity Score = 0 : hypodensity of the entire middle cerebral artery (MCA)territory A score =7 = pejorative prognosis in terms of both residual disability and risk of haemorrhagic transformation |
At 24hours (±6) hours | |
Secondary | Efficacy outcomes : Type and dose of antiplatelet agents administered | Type and dose of antiplatelet agents administered during the procedure, at 24 (±6) hours, at discharge (5-7 days). | at 24 (±6) hours, at discharge (5-7 days) | |
Secondary | Efficacy outcomes : Rate of recurrent clinical ischemic event | Rate of recurrent clinical ischemic event at 90 (±15) days in the ipsilateral carotid territory | at 90 days for rate of recurrent clinical ischemic event | |
Secondary | Efficacy outcomes : Rate of functional independence | - Rate of functional independence defined as a modified Rankin Scale (mRS) score 0-2 at 90 (±15 days) and 12 months (blind and independent evaluation) The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The Modified Rankin Score (mRS) is the most widely used outcome measure in stroke clinical trials. Standardized interviews to obtain a mRS score are recommended at 3 months (90 days) following hospital discharge. | at 90 days and 12 months for mRS | |
Secondary | Safety outcomes : Rate of procedural complications | Rate of procedural complications: vascular perforation, arterial dissection, embolization to new territory, access site complication requiring surgical repair or blood transfusion, intra-procedural mortality, and device failure | At the end of endovascular procedure | |
Secondary | Safety outcomes : Rates of carotid stenosis and stent thrombosis | Rates of carotid stenosis and stent thrombosis at the end of the endovascular procedure | At the end of endovascular procedure | |
Secondary | Safety outcomes : Rate of symptomatic and asymptomatic intracerebral hemorrhage | Rate of symptomatic and asymptomatic intracerebral hemorrhage at CT (Computerized Tomography) or MRI (Magnetic Resonance Imaging) at 24 hours (±6 hours) according to the Heidelberg classification (independent imaging core laboratory) | at 24 hours (±6 hours) | |
Secondary | Safety outcomes : Rate of carotid stenosis and stent thrombosis | Rate of carotid stenosis (NASCET : North American Symptomatic Carotid Endarterectomy Trial Collaborators), and stent thrombosis at 24 (±6) hours on Computerized Tomography Angiography (CTA) or Magnetic Resonance Angiography (MRA) | at 24 (±6) hours | |
Secondary | Safety outcomes :Rate of secondary decompressive craniotomy | Rate of secondary decompressive craniotomy at discharge (5-7 days) | at discharge (or 5-7 days) | |
Secondary | Safety outcomes : Rate of endarterectomy | Rate of endarterectomy at 90 (±15) days, and 12 (±1) months | at 90 days and 12 (±1) months | |
Secondary | Safety outcomes : Rate of mortality | Rate of mortality at 24 (±6) hours, 90 (±15) days, and 12 (±1) months | at 24 (±6) hours, 90 (±15) days, and 12 (±1) months | |
Secondary | Cost effectiveness outcomes : value the additional cost of gaining additional clinical (NIHSS) | A cost-effectiveness analysis on secondary outcome criteria will be conducted to value the additional cost of gaining additional clinical benefit at 24 hours (NIHSS), and at 3 months (mRS), especially in terms of functional ability, using an incremental cost-effectiveness ratio. The result will be presented as cost per additional case of disability averted. | At 24 hours | |
Secondary | Cost effectiveness outcomes : value the additional cost of gaining additional clinical (mRS) | A cost-effectiveness analysis on secondary outcome criteria will be conducted to value the additional cost of gaining additional clinical benefit at 24 hours (NIHSS), and at 3 months (mRS), especially in terms of functional ability, using an incremental cost-effectiveness ratio. The result will be presented as cost per additional case of disability averted. | at 3 months | |
Secondary | Cost effectiveness outcomes : cost of safety issues | Cost of safety issues will be considered. The time horizon will be at 3 months. The analysis will be conducted in the National Health Insurance System (NHIS) perspective. For this purpose, the investigators will classify each patient's stay in the appropriate Diagnosis-Related Group (DRG). | At 3 months | |
Secondary | Cost effectiveness outcomes : a cost-utility analysis | in a perspective of generic comparison, a cost-utility analysis will be conducted by using quality of life scores collected at 12 months of the intervention. The objective is to estimate the cost by one quality-adjusted life year (QALY) gained. | At 12 months | |
Secondary | Cost effectiveness outcomes : a budget impact analysis | a budget impact analysis will be performed. The objective is to estimate the total cost of adopting the combined approach of treatment at the national level and the expected number of disability cases averted. | At 12 months |
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