Carotid Artery DiseasesTITANNCT03978988
Thrombectomy In TANdem Occlusion
A study testing Carotid Stenting, Procedural Aspirin and Dual dual antiplatelet therapy after 24-hours imaging follow-up in people with Carotid Artery Diseases and Thrombectomy, run by Central Hospital, Nancy, France at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carotid Artery Diseases, Thrombectomy, Tandem Occlusion
- What is being tested?
- Carotid Stenting, Procedural Aspirin and Dual dual antiplatelet therapy after 24-hours imaging follow-up
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 432 participants
- Where
- 1 siteFrance
- Study dates
- 29 Apr 2020to 6 Mar 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 :
Show all 17Show fewer
- -> 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
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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.
Read the detailed description
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 :
- 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).
- To compare the safety of intracranial thrombectomy and extracranial carotid stenting compared to intracranial thrombectomy alone.
- 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
- Conditions
- Carotid Artery Diseases, Thrombectomy, Tandem Occlusion, Stroke
- Being tested
- Carotid Stenting, Procedural Aspirin, Dual dual antiplatelet therapy after 24-hours imaging follow-up, Intracranial thrombectomy
- Keywords
- stroke, tandem occlusion, carotid stenting, thrombectomy
- Medical subject headings
- Carotid Artery Diseases, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carotid StentingDevice
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.
Procedural AspirinDrug
After carotid stenting, an intravenous bolus of 250mg of Aspirin will be given at the end of the procedure in case of absence of complication.
Dual dual antiplatelet therapy after 24-hours imaging follow-upDrug
A dual antiplatelet therapy is administered after 24-hours imaging follow-up excluding intracranial hemorrhagic complications (the type and the dose of the dual antiplatelet therapy are left to the discretion of the local practice)
Intracranial thrombectomyProcedure or surgery
Intracranial thrombectomy is the endovascular procedure. In the experimental group, thrombectomy will be completed with a extracranial carotid stenting.
| Study group | Role | What they receive |
|---|---|---|
| Thrombectomy + Carotid Stenting | Experimental | 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) Receives: Device: Carotid Stenting; Drug: Procedural Aspirin; Drug: Dual dual antiplatelet therapy after 24-hours imaging follow-up; Procedure: Intracranial thrombectomy |
| Thrombectomy alone | No intervention | Endovascular procedure: Intracranial thrombectomy alone (carotid angioplasty may be performed) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at the end of angiography(mTICI score) , at 24 hours (NIHSS score)
Secondary outcomes (20)
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
Measured: at the end of the endovascular procedure
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.
Measured: at 24 hours (±6) hours
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
Measured: at the end of the endovascular procedure
Efficacy outcomes : Number of passes
Number of intracranial thrombectomy passes to achieve final reperfusion
Measured: at the end of the endovascular procedure
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
Measured: At 24hours (±6) hours
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).
Measured: at 24 (±6) hours, at discharge (5-7 days)
Efficacy outcomes : Rate of recurrent clinical ischemic event
Rate of recurrent clinical ischemic event at 90 (±15) days in the ipsilateral carotid territory
Measured: at 90 days for rate of recurrent clinical ischemic event
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.
Measured: at 90 days and 12 months for mRS
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
Measured: At the end of endovascular procedure
Safety outcomes : Rates of carotid stenosis and stent thrombosis
Rates of carotid stenosis and stent thrombosis at the end of the endovascular procedure
Measured: At the end of endovascular procedure
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)
Measured: at 24 hours (±6 hours)
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)
Measured: at 24 (±6) hours
Safety outcomes :Rate of secondary decompressive craniotomy
Rate of secondary decompressive craniotomy at discharge (5-7 days)
Measured: at discharge (or 5-7 days)
Safety outcomes : Rate of endarterectomy
Rate of endarterectomy at 90 (±15) days, and 12 (±1) months
Measured: at 90 days and 12 (±1) months
Safety outcomes : Rate of mortality
Rate of mortality at 24 (±6) hours, 90 (±15) days, and 12 (±1) months
Measured: at 24 (±6) hours, 90 (±15) days, and 12 (±1) months
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.
Measured: At 24 hours
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.
Measured: at 3 months
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).
Measured: At 3 months
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.
Measured: At 12 months
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.
Measured: At 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2019
- Study start29 Apr 2020
- Primary completion8 Mar 2025
- Study completion6 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carotid Artery DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 432 participants (actual)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Benjamin GORY, MD, PhD, Central Hospital, Nancy, France
- Investigators
- Benjamin GORY, PhD, Principal investigator, CHRU de Nancy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03978988
- Sponsor's protocol ID
- 2019-A01085-52
- Acronym
- TITAN
- Status last verified
- Jun 2025
- First submitted
- 29 May 2019
- Last updated
- 5 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Zhu F, Hossu G, Soudant M, Richard S, Achit H, Beguinet M, Costalat V, Arquizan C, Consoli A, Lapergue B, Rouchaud A, Macian-Montoro F, Biondi A, Moulin T, Marnat G, Sibon I, Paya C, Vannier S, Cognard C, Viguier A, Mazighi M, Obadia M, Hassen WB, Turc G, Clarencon F, Samson Y, Dumas-Duport B, Preterre C, Barbier C, Boulanger M, Janot K, Annan M, Bricout N, Henon H, Soize S, Moulin S, Labeyrie MA, Reiner P, Pop R, Wolff V, Ognard J, Timsit S, Reyre A, Perot C, Papagiannaki C, Triquenot-Bagan A, Bracard S, Anxionnat R, Derelle AL, Tonnelet R, Liao L, Schmitt E, Planel S, Guillemin F, Gory B. Effect of emergent carotid stenting during endovascular therapy for acute anterior circulation stroke patients with tandem occlusion: A multicenter, randomized, clinical trial (TITAN) protocol. Int J Stroke. 2021 Apr;16(3):342-348. doi: 10.1177/1747493020929948. Epub 2020 Jun 9.
PubMed 32515696
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intracranial Thrombectomy and Extracranial Carotid Stenting Versus Intracranial Thrombectomy Alone In Acute Anterior Circulation Strokes With TANdem Occlusion : the Randomized Controlled TITAN Trial
- ClinicalTrials.gov ID
- NCT03978988
- Acronym / sponsor ID
- TITAN / 2019-A01085-52
- Conditions
- Carotid Artery Diseases, Thrombectomy, Tandem Occlusion, Stroke
- Keywords
- stroke, tandem occlusion, carotid stenting, thrombectomy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 432 participants (actual)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 29 Apr 2020 (actual)
- Primary completion
- 8 Mar 2025 (actual)
- Study completion
- 6 Mar 2026 (estimated)
- First posted
- 7 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 :
- 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).
- To compare the safety of intracranial thrombectomy and extracranial carotid stenting compared to intracranial thrombectomy alone.
- 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
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thrombectomy + Carotid Stenting | Experimental | Device: Carotid Stenting, Drug: Procedural Aspirin, Drug: Dual dual antiplatelet therapy after 24-hours imaging follow-up, Procedure: Intracranial thrombectomyIntravenous 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) |
| Thrombectomy alone | No intervention | –Endovascular procedure: Intracranial thrombectomy alone (carotid angioplasty may be performed) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carotid Stentingemergent 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. | Device | Thrombectomy + Carotid Stenting |
| Procedural AspirinAfter carotid stenting, an intravenous bolus of 250mg of Aspirin will be given at the end of the procedure in case of absence of complication. | Drug | Thrombectomy + Carotid Stenting |
| Dual dual antiplatelet therapy after 24-hours imaging follow-upA dual antiplatelet therapy is administered after 24-hours imaging follow-up excluding intracranial hemorrhagic complications (the type and the dose of the dual antiplatelet therapy are left to the discretion of the local practice) | Drug | Thrombectomy + Carotid Stenting |
| Intracranial thrombectomyIntracranial thrombectomy is the endovascular procedure. In the experimental group, thrombectomy will be completed with a extracranial carotid stenting. | Procedure or surgery | Thrombectomy + Carotid Stenting |
Primary outcome
Change in Modified treatment in cerebral ischemia (mTICI) score AND National Institutes of Health Stroke Scale (NIHSS) score
Time frame: 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.
20 secondary outcomes
Efficacy outcomes : Rate of reperfusion with change in Modified treatment in cerebral ischemia (mTICI) score
Time frame: at the end of the endovascular procedure
Efficacy outcomes : Change in National Institutes of Health Stroke Scale (NIHSS) score
Time frame: at 24 hours (±6) hours
Efficacy outcomes : number of participants with delays of symptoms
Time frame: at the end of the endovascular procedure
Efficacy outcomes : Number of passes
Time frame: at the end of the endovascular procedure
Efficacy outcomes : Infarct growth (volume)
Time frame: At 24hours (±6) hours
Efficacy outcomes : Type and dose of antiplatelet agents administered
Time frame: at 24 (±6) hours, at discharge (5-7 days)
Efficacy outcomes : Rate of recurrent clinical ischemic event
Time frame: at 90 days for rate of recurrent clinical ischemic event
Efficacy outcomes : Rate of functional independence
Time frame: at 90 days and 12 months for mRS
Safety outcomes : Rate of procedural complications
Time frame: At the end of endovascular procedure
Safety outcomes : Rates of carotid stenosis and stent thrombosis
Time frame: At the end of endovascular procedure
Safety outcomes : Rate of symptomatic and asymptomatic intracerebral hemorrhage
Time frame: at 24 hours (±6 hours)
Safety outcomes : Rate of carotid stenosis and stent thrombosis
Time frame: at 24 (±6) hours
Safety outcomes :Rate of secondary decompressive craniotomy
Time frame: at discharge (or 5-7 days)
Safety outcomes : Rate of endarterectomy
Time frame: at 90 days and 12 (±1) months
Safety outcomes : Rate of mortality
Time frame: at 24 (±6) hours, 90 (±15) days, and 12 (±1) months
Cost effectiveness outcomes : value the additional cost of gaining additional clinical (NIHSS)
Time frame: At 24 hours
Cost effectiveness outcomes : value the additional cost of gaining additional clinical (mRS)
Time frame: at 3 months
Cost effectiveness outcomes : cost of safety issues
Time frame: At 3 months
Cost effectiveness outcomes : a cost-utility analysis
Time frame: At 12 months
Cost effectiveness outcomes : a budget impact analysis
Time frame: At 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- Derived from this study: PubMed 32515696Zhu F, Hossu G, Soudant M, Richard S, Achit H, Beguinet M, Costalat V, Arquizan C, Consoli A, Lapergue B, Rouchaud A, Macian-Montoro F, Biondi A, Moulin T, Marnat G, Sibon I, Paya C, Vannier S, Cognard C, Viguier A, Mazighi M, Obadia M, Hassen WB, Turc G, Clarencon F, Samson Y, Dumas-Duport B, Preterre C, Barbier C, Boulanger M, Janot K, Annan M, Bricout N, Henon H, Soize S, Moulin S, Labeyrie MA, Reiner P, Pop R, Wolff V, Ognard J, Timsit S, Reyre A, Perot C, Papagiannaki C, Triquenot-Bagan A, Bracard S, Anxionnat R, Derelle AL, Tonnelet R, Liao L, Schmitt E, Planel S, Guillemin F, Gory B. Effect of emergent carotid stenting during endovascular therapy for acute anterior circulation stroke patients with tandem occlusion: A multicenter, randomized, clinical trial (TITAN) protocol. Int J Stroke. 2021 Apr;16(3):342-348. doi: 10.1177/1747493020929948. Epub 2020 Jun 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin GORY, PhD principal investigator
CHRU de Nancy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carotid Stenting, Procedural Aspirin and Dual dual antiplatelet therapy after 24-hours imaging follow-up in people with Carotid Artery Diseases and Thrombectomy, run by Central Hospital, Nancy, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Modified treatment in cerebral ischemia (mTICI) score AND National Institutes of Health Stroke Scale (NIHSS) score (time frame: at the end of angiography(mTICI score) , at 24 hours (NIHSS score)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03978988, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2025; AzTrials last refreshed its copy on 27 Oct 2026.