Stent Implantation Versus Balloon Dilation for Acute Anterior Circulation Tandem Occlusion

Stroke Clinical Trial

— START  

Official title:

Stent Implantation Versus Balloon Dilation for Acute Anterior Circulation Tandem Occlusion: A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05902000
• Other study ID #: WKJ-ZJ-2327
• Status: Recruiting
• Phase: N/A
• Start date: June 14, 2023
• Est. completion date: December 2025

Study information

• Verified date: June 2023
• Source: Lishui Municipal Central Hospital
• Contact: Li X Cai Xueli, Ph.D
• Phone: 86-13967059836
• Email: xueli_cai_official[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

1. To evaluate whether stent implantation on the ipsilateral extracranial segment, after intracranial thrombectomy successful recanalization compared with balloon angioplasty (eTICI≥2b_50) for acute anterior circulation tandem lesions within 24h of onset, can improve neurological functional outcomes(mRS≤2). 2. To evaluate whether stent implantation on the ipsilateral extracranial segment, after intracranial thrombectomy successful recanalization compared with balloon angioplasty (eTICI≥2b_50) for acute anterior circulation tandem lesions within 24h of onset, can increase the risk of symptomatic intracranial hemorrhage.

Description:

The study was a prospective, randomized, open-label, blinded end-point Clinical Trial. Subjects were randomized 1:1 according to inclusion and exclusion criteria into a trial group (acute phase extracranial vascular stent implantation group) and a control group (acute phase non-extracranial vascular stent implantation group). Randomization was performed for 90d and 180d for the follow-up to collect primary and secondary efficacy and safety indicators.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 222
• Est. completion date: December 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

General inclusion criteria

1. Age 18-85 years old;

2. Acute ischemic stroke and the onset time within 24h;

3. Pre-stroke mRS 0-1;

4. NIHSS score of 6-30 before randomization;

5. Completed randomization within 24h after stroke onset;

6. Subjects are able to sign an informed consent in person or by the legal representative

Imaging Inclusion Criteria:

1. Satisfy one of the following criteria:?Within 6 hours of onset, imaging confirmed occlusion of the acute anterior circulation internal carotid artery or the M1 / M2 segment of the middle cerebral artery;?Within 6-16 hours of onset, imaging confirmed acute occlusion of anterior circulation internal carotid artery or M1 / M2 segment of middle cerebral artery followed by DAWN or DEFUSE-3 criteria;?In patients with 16 to 24 hours of onset, imaging confirmed intracranial occlusion of the acute anterior circulation internal carotid artery or M1 / M2 segment of the middle cerebral artery followed by DAWN criteria.

2. Extracranial segment stenosis =70% or occlusion in tandem lesions.

3. ASPECT score = 6 points.

4. eTICI=2b_50 after middle cerebral artery thrombectomy and extracranial balloon dilatation in 10min. General Exclusion Criteria: Participating in other clinical trials; 2.It is planned to carry out selective internal carotid artery stent implantation within 3 months; 3.Intracranial hemorrhage, subarachnoid hemorrhage within 3 months; previous brain tumor (with space-occupying effect). 4.Parenchymal organ surgery or biopsy were performed last 1 month; Any active or recent bleeding (gastrointestinal, urinary, etc.); Parenchymal organ surgery and biopsy were performed last 1 month 5.Difficult to control hypertension: systolic blood pressure> 185mmHg and/ or diastolic blood pressure> 110mmHg. 6.Severe active bleeding or known significant bleeding tendency: platelet count <100X109/L; heparin within 48 hours before surgery, and APTT=35s; oral warfarin, and INR> 1.7; direct thrombin or factor Xa inhibitors, such as apixaban tablets, rivaroxaban tablets and dabigatran (patients with no history of abnormal coagulation or suspected abnormal coagulation function do not need laboratory results of INR or APTT before enrollment). 7.Severe heart, liver, kidney, and other organ insufficiencies (glomerular filtration rate <30 ml/min or blood creatinine> 220µmol/L(2.5mg/dl)). 8.Patients occurred acute ischemic cerebral infarction within 48 hours after percutaneous coronary or cerebrovascular intervention or major surgery (if more than 48h, patients may be enrolled).

9. The patient has a history of cerebral vasculitis with clear evidence; 10. Patients with pre-onset neurological or psychiatric disorders that affect the assessment of their condition 11.Women who are known to be pregnant or lactating. 12.Known severe allergy to contrast agents (except for mild rash allergy) 13.Expected survival time less than 1 year (such as combined malignancy, severe cardiopulmonary disease, etc.) 14.Patients unable to complete the follow up (e. g., no fixed residence, overseas patients, etc.).

Imaging exclusion criterias:

1. Imaging confirmed the posterior circulatory lesions.

2. Midline displacement of the brain or brain herniation, ventricular occupancy

3. New onset bilateral acute stroke or multiple intracranial macrovascular occlusions.

4. Patients with vascular variants that are difficult to treat with endovascular therapy as displayed by CTA/MRA;

5. The ipsilateral middle cerebral artery and anterior cerebral occlusion were combined.

Related Conditions & MeSH terms

• Stroke
• Tandem Occlusion
• Thrombectomy

Intervention

Device:
• Carotid Stenting
Emergent carotid stenting will be performed if the patient is randomized in the intervention arm. The order to treat (head first or neck first) the extracranial carotid artery lesion will be left to the interventionist discretion.

Procedure:
• Thrombectomy
Intracranial thrombectomy is an endovascular procedure. In the experimental group, thrombectomy will be completed with extracranial carotid stenting.

Drug:
• Dual antiplatelet treatment
Dual antiplatelet therapy is administered after 24 hours of imaging follow-up excluding intracranial hemorrhagic complications. Aspirin Enteric-coated Tablets (Bay Aspirin) 100mg once a night+Clopidogrel Sulfate Tablets (Plavix) 75mg once daily. If there is no contraindication, maintain for more than 1 month, then adjust the dosing regimen according to the guidelines.
• Intraoperative Drug Treatment
Tirofiban is used as an adjunct to endovascular therapy. The currently recommended dosing regimen is a combined intra-catheter arterial administration of a loading dose of 0.4 µg/(kg-min) for 30 min (total dose not to exceed 1 mg), followed by intravenous pumping of 0.1µg/(kg-min) for 24-48h, and adjustment of dosing in conjunction with CT.

Locations

Country	Name	City	State
China	Lishui Municipal Hospital	Lishui	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Xueli Cai

Country where clinical trial is conducted

China, 

References & Publications (15)

Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demch — View Citation

Anadani M, Spiotta AM, Alawieh A, Turjman F, Piotin M, Haussen DC, Nogueira RG, Papanagiotou P, Siddiqui AH, Lapergue B, Dorn F, Cognard C, Ribo M, Psychogios MN, Labeyrie MA, Mazighi M, Biondi A, Anxionnat R, Bracard S, Richard S, Gory B; TITAN (Thrombec — View Citation

Berkhemer OA, Majoie CB, Dippel DW; MR CLEAN Investigators. Endovascular therapy for ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2363. doi: 10.1056/NEJMc1504715. No abstract available. — View Citation

Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGu — View Citation

Feil K, Herzberg M, Dorn F, Tiedt S, Kupper C, Thunstedt DC, Papanagiotou P, Meyer L, Kastrup A, Dimitriadis K, Liebig T, Dieterich M, Kellert L; GSR investigatorsdagger. Tandem Lesions in Anterior Circulation Stroke: Analysis of the German Stroke Registr — View Citation

Fox AJ. How to measure carotid stenosis. Radiology. 1993 Feb;186(2):316-8. doi: 10.1148/radiology.186.2.8421726. No abstract available. — View Citation

Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Cho — View Citation

Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, — View Citation

Kim YS, Garami Z, Mikulik R, Molina CA, Alexandrov AV; CLOTBUST Collaborators. Early recanalization rates and clinical outcomes in patients with tandem internal carotid artery/middle cerebral artery occlusion and isolated middle cerebral artery occlusion. — View Citation

Li W, Chen Z, Dai Z, Liu R, Yin Q, Wang H, Hao Y, Han Y, Qiu Z, Xiong Y, Sun W, Zi W, Xu G, Liu X. Management of acute tandem occlusions: Stent-retriever thrombectomy with emergency stenting or angioplasty. J Int Med Res. 2018 Jul;46(7):2578-2586. doi: 10 — View Citation

Mueller-Kronast NH, Zaidat OO, Froehler MT, Jahan R, Aziz-Sultan MA, Klucznik RP, Saver JL, Hellinger FR Jr, Yavagal DR, Yao TL, Liebeskind DS, Jadhav AP, Gupta R, Hassan AE, Martin CO, Bozorgchami H, Kaushal R, Nogueira RG, Gandhi RH, Peterson EC, Dashti — View Citation

Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, V — View Citation

Pires Coelho A, Lobo M, Gouveia R, Silveira D, Campos J, Augusto R, Coelho N, Canedo A. Overview of evidence on emergency carotid stenting in patients with acute ischemic stroke due to tandem occlusions: a systematic review and meta-analysis. J Cardiovasc — View Citation

Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan — View Citation

Zhu F, Bracard S, Anxionnat R, Derelle AL, Tonnelet R, Liao L, Mione G, Humbertjean L, Lacour JC, Hossu G, Anadani M, Richard S, Gory B. Impact of Emergent Cervical Carotid Stenting in Tandem Occlusion Strokes Treated by Thrombectomy: A Review of the TITA — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of functional independence	Rate of functional independence defined as a modified Rankin Scale (mRS) score 0-2 at 90 (±7 days) (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±7 days
Primary	Rate of symptomatic intracranial hemorrhage	Rate of symptomatic intracerebral hemorrhage at CT (Computerized Tomography) or MRI (Magnetic Resonance Imaging) at 36 hours (±12 hours) according to the Heidelberg classification (independent imaging core laboratory).	at 36 hours (±12 hours)
Secondary	The expanded treatment in cerebral infarction (eTICI) score	eTICI score (0,1,2a,2a_50,2a_67,2c,3) : Grade 0 : no perfusion Grade 1: penetration with minimal perfusion Grade 2a: partial filling of 1-49% of the vascular territory Grade 2b_50 : partial filling of 50-66% of the vascular territory Grade 2b_67: partial filling of 67-89% of the vascular territory Grade 2c: partial filling of 90-99% of the vascular territory Grade 3 : complete perfusion	at the end of the endovascular procedure
Secondary	Ipsilateral carotid residual stenosis rate	The extracranial stenosis was assessed by using criteria from the North American Symptomatic Carotid Endarterectomy Trial (NASCET). The residual stenosis rate of the ipsilateral internal carotid artery was assessed according to the last DSA angiography of the procedure.	at the end of the endovascular procedure
Secondary	The National Institutes of Health Stroke Scale (NIHSS) score	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.; Higher scores mean a worse outcome.	at 36 hours (±12 hours)
Secondary	Proportion of NIHSS scores 0-1	The proportion of patients with an NIHSS score of 0-1; 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.; Higher scores mean a worse outcome.	at 36 hours (±12 hours)
Secondary	Change in National Institutes of Health Stroke Scale (NIHSS) score	The proportion of patients with an NIHSS score reduction of =4 points after randomization compared to baseline.; NIHSS is 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.; Higher scores mean a worse outcome.	at 36 hours (±12 hours)
Secondary	Rate of carotid stenosis	The extracranial stenosis was assessed by using criteria from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) confirmed by cervical vascular ultrasound.	at 5-7days or discharge
Secondary	The NIHSS score	The NIHSS score; NIHSS is 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.; Higher scores mean a worse outcome.	at 5-7days or discharge
Secondary	The mRS scores	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±7days and 180±14 days
Secondary	Proportion of mRS score 0-3	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 an mRS score are recommended at 3 months (90 days) following hospital discharge.; Higher scores mean a worse outcome.	at 90±7days and 180±14 days
Secondary	All-cause mortality	Rate of mortality at 90±14 days.	at 90±7days
Secondary	Rate of asymptomatic intracranial hemorrhage	Rate of symptomatic intracerebral hemorrhage at CT (Computerized Tomography) or MRI (Magnetic Resonance Imaging) at 36 hours (±12 hours) according to the Heidelberg classification (independent imaging core laboratory).	at 36 hours (±12 hours)
Secondary	The incidence of adverse events.	Any adverse medical event, whether causally related to the trial or not, that occurred between the start of patient randomization and the last follow-up visit was judged as an adverse event. The incidence of non-hemorrhagic adverse events.	at 90±7days and 180±14 days
Secondary	The incidence of serious adverse events.	A serious adverse event is defined as an adverse event that results in; Resulting in death; Life-threatening (means that the subject is at risk of death at the time of an adverse event. It does not refer to those adverse events that could lead to death if the condition were assumed to be worse); Requires hospitalization or prolonged hospitalization; Resulting in persistent or severe disability or dysfunction; Resulting in a congenital anomaly or birth defect; Medical events that, in the opinion of the investigator, can be judged as serious adverse events.; The incidence of non-hemorrhagic serious adverse events.	at 90±7days and 180±14 days