Clinical trial NCT05902000: Stent Implantation Versus Balloon Dilation for Acute Anterior Circulation Tandem Occlusion
Official title: Stent Implantation Versus Balloon Dilation for Acute Anterior Circulation Tandem Occlusion: A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Thrombectomy
Tandem Occlusion
Stroke
Keywords: tandem occlusion
anterior circulation
stent implantation
balloon dilation
randomized controlled trial
Lead sponsor: Lishui Municipal Central Hospital
Sponsor class: OTHER_GOV
First posted: 2023-06-13
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Carotid artery stenting after intracranial or middle cerebral artery embolization and balloon dilation of the extracranial segment of the ipsilateral internal carotid artery
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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:①Within 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；②Within 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；③In 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.

Primary outcomes:
measure: Rate of functional independence
timeFrame: at 90±7 days
measure: Rate of symptomatic intracranial hemorrhage
timeFrame: at 36 hours (±12 hours)
Secondary outcomes:
measure: The expanded treatment in cerebral infarction (eTICI) score
timeFrame: at the end of the endovascular procedure
measure: Ipsilateral carotid residual stenosis rate
timeFrame: at the end of the endovascular procedure
measure: The National Institutes of Health Stroke Scale (NIHSS) score
timeFrame: at 36 hours (±12 hours)
measure: Proportion of NIHSS scores 0-1
timeFrame: at 36 hours (±12 hours)
measure: Change in National Institutes of Health Stroke Scale (NIHSS) score
timeFrame: at 36 hours (±12 hours)
measure: Rate of carotid stenosis
timeFrame: at 5-7days or discharge
measure: The NIHSS score
timeFrame: at 5-7days or discharge
measure: The mRS scores
timeFrame: at 90±7days and 180±14 days
measure: Proportion of mRS score 0-3
timeFrame: at 90±7days and 180±14 days
measure: All-cause mortality
timeFrame: at 90±7days
measure: Rate of asymptomatic intracranial hemorrhage
timeFrame: at 36 hours (±12 hours)
measure: The incidence of adverse events.
timeFrame: at 90±7days and 180±14 days
measure: The incidence of serious adverse events.
timeFrame: at 90±7days and 180±14 days
Other outcomes:
Locations:
city: Lishui
country: China
facility: Lishui Municipal Hospital
state: Zhejiang
Study officials:
affiliation: Lishui Municipal Hospital
name: Li X Cai
role: PRINCIPAL_INVESTIGATOR
References:
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.
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, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.
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, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.
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 R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.
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, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.
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, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG; DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4;378(1):11-21. doi: 10.1056/NEJMoa1706442. Epub 2017 Nov 11.
citation: 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, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG; DEFUSE 3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Feb 22;378(8):708-718. doi: 10.1056/NEJMoa1713973. Epub 2018 Jan 24.
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. Stroke. 2005 Apr;36(4):869-71. doi: 10.1161/01.STR.0000160007.57787.4c. Epub 2005 Mar 3.
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 SR, Given CA 2nd, Mehta BP, Deshmukh V, Starkman S, Linfante I, McPherson SH, Kvamme P, Grobelny TJ, Hussain MS, Thacker I, Vora N, Chen PR, Monteith SJ, Ecker RD, Schirmer CM, Sauvageau E, Abou-Chebl A, Derdeyn CP, Maidan L, Badruddin A, Siddiqui AH, Dumont TM, Alhajeri A, Taqi MA, Asi K, Carpenter J, Boulos A, Jindal G, Puri AS, Chitale R, Deshaies EM, Robinson DH, Kallmes DF, Baxter BW, Jumaa MA, Sunenshine P, Majjhoo A, English JD, Suzuki S, Fessler RD, Delgado Almandoz JE, Martin JC, Haussen DC; STRATIS Investigators. Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry. Stroke. 2017 Oct;48(10):2760-2768. doi: 10.1161/STROKEAHA.117.016456. Epub 2017 Aug 22.
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: 10.1177/0300060518765310. Epub 2018 May 4.
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 Registry-Endovascular Treatment. Stroke. 2021 Apr;52(4):1265-1275. doi: 10.1161/STROKEAHA.120.031797. Epub 2021 Feb 16.
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 TITAN Collaboration. Front Neurol. 2019 Mar 11;10:206. doi: 10.3389/fneur.2019.00206. eCollection 2019.
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 Surg (Torino). 2019 Dec;60(6):693-702. doi: 10.23736/S0021-9509.18.10312-0. Epub 2018 Jan 23.
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 (Thrombectomy In TANdem Lesions) Investigators. Emergent Carotid Stenting Plus Thrombectomy After Thrombolysis in Tandem Strokes: Analysis of the TITAN Registry. Stroke. 2019 Aug;50(8):2250-2252. doi: 10.1161/STROKEAHA.118.024733. Epub 2019 Jun 17.
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.