Intra-arterial Tenecteplase for Acute Medium Vessel Occlusion Stroke

NCT07357987 | Recruiting Phase 3 DMC

• 1 other identifier: ANGEL-MeVO-TNK
• Study Type: interventional
• Target: 488
• Locations: 1 country
• Sites: 1

Brief Summary

The ANGEL-MeVO-TNK is a multicentered, prospective, randomized, open label, blinded endpoint (PROBE) phase III trial. A total of 488 AIS patients (age ≥18 years) with acute MeVO-AIS (occlusion of the M2/M3, the A1/A2/A3, the P1/P2/P3, and with baseline NIHSS score \>5 or disabling stroke with NIHSS score 3-5 \[such as neurological deficits in motor strength, language, vision, etc\]), will be enrolled. Patients fulfilling all the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into the IA TNK group or the control group after offering informed content.

• The IA TNK group：1) If the patient has not received IVT, IA TNK will be administered as a slow, continuous infusion for super-selective contact thrombolysis in a stepwise manner: an initial dose of 0.0625 mg/kg with a duration of 15 minutes. A repeat angiographic assessment will then be performed; if recanalization is not achieved, an additional dose of 0.0625 mg/kg will be administered over a further 15 minutes (maximum dose 12.5 mg) . 2\) If the patient has received IVT, intra-arterial TNK will be administered as a slow infusion for super-selective contact thrombolysis at a dose of 0.0625 mg/kg (maximum dose 6.25 mg) with a duration of 15 minutes.
• The control group will be given standard medical management. The study consists of four visits including the day of randomization, 48±12 hours after randomization, and 90±7 days after randomization. Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment neurological function rating scale will be recorded during the program. The primary outcome is the modified Rankin Scale (mRS) score of 0 to 1 at 90±7 days after onset. The primary safety outcome is the incidence of sICH within 48±12 hours after randomization (ECASS III).

Conditions

Ischemic Stroke; Medium Vessel Occlusion; Tenecteplase; Endovascular Treatment

Outcome Measures

Primary Outcomes (2)

• mRS score of 0 to 1 at 90±7 days after onset

  The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death.

  90±7 days after onset

• symptomatic intracerebral hemorrhage within 48±12 hours after randomization

  symptomatic intracerebral hemorrhage (sICH) within 48±12 hours after randomization (ECASS III criteria)

  48±12 hours after randomization

Secondary Outcomes (8)

• Ordinal mRS score at 90±7 days after onset

  90±7 days after onset

• mRS score 0 to 2 at 90±7 days after onset

  90±7 days after onset

• mRS score 0 to 3 at 90±7 days after onset

  90±7 days after onset

• Number of Participants with Recanalization of the target occluded artery within 48 ± 12 hours after randomization

  48 ± 12 hours after randomization

• Infarct volume at 48 ± 12 hours after randomization

  48 ± 12 hours after randomization

Study Arms (2)

IA TNK group

EXPERIMENTAL

During thrombolysis, once vessel recanalization is achieved, immediate termination of the infusion is recommended. If thrombus migration, residual distal embolization, or other situations occur during drug administration, the operator may decide whether to continue treatment at their discretion. Otherwise, TNK will be administered at the specified dose and infusion rate and repeat angiography will be performed after 15 or 30 minutes, followed by termination of the procedure. After completion of the procedure, patients will receive standard medical management as recommended by current guidelines#

Procedure: Intra-arterial Tenecteplase

Control group (Standard medical management group)

ACTIVE COMPARATOR

Patients will receive standard medical management as recommended by current guidelines# #《Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke (2023)》and《Chinese Guidelines for Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack (2022)》

Drug: standard medical management

Interventions

Intra-arterial Tenecteplase PROCEDURE

1. If the patient has not received IVT, IA TNK will be administered as a slow, continuous infusion for super-selective contact thrombolysis in a stepwise manner: an initial dose of 0.0625 mg/kg with a duration of 15 minutes. A repeat angiographic assessment will then be performed; if recanalization is not achieved, an additional dose of 0.0625 mg/kg will be administered over a further 15 minutes (maximum dose 12.5 mg) . 2. If the patient has received IVT, intra-arterial TNK will be administered as a slow infusion for super-selective contact thrombolysis at a dose of 0.0625 mg/kg (maximum dose 6.25 mg) with a duration of 15 minutes.

IA TNK group

standard medical management DRUG

Patients will receive standard medical management as recommended by current guidelines# #《Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke (2023)》and《Chinese Guidelines for Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack (2022)》

Control group (Standard medical management group)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years;
• Pre-stroke mRS 0-1;
• Within 24 h from symptom onset;
• Baseline National Institutes of Health Stroke Scale (NIHSS) score \>5 or baseline NIHSS 3-5 with disabling deficit (e.g., loss of hand function, aphasia, hemianopia);
• Informed consent obtained from patients or their legal representatives.
• Baseline CTA/MRA/DSA diagnosed isolated MeVO, referring to the M2/M3 segment of the MCA, the A1/A2/A3 segment of the ACA, the P1/P2/P3 segment of the PCA;
• NCCT or MRI DWI imaging showing that the territory of the ischemic infarct volume is less than 50% of the estimated territory supplied by the occluded artery.

You may not qualify if:

• Acute intracranial hemorrhage;
• ASPECT ≤5;
• MeVO secondary to spontaneous fragmentation and distal migration of thrombus from an acute large vessel occlusion, or occurring after intravenous thrombolysis (IVT), intra-arterial thrombolysis, or endovascular thrombectomy;
• Contraindication to TNK;
• Known severe allergy to contrast agents (excluding mild rash-type allergic reactions);
• Use of heparin or novel oral anticoagulants within the previous 48 hours with an INR ≥ 1.7;
• A history of major bleeding within the past 6 months or the presence of conditions such as active gastrointestinal ulcer, aortic dissection, platelet count \< 100 × 10⁹/L, etc.;
• Radiologically confirmed vascular malformations, arterial dissection, intracranial aneurysm (diameter≥3 mm), tumors (except small meningiomas), cerebral vasculitis, cerebral amyloid angiopathy, or other major non-ischemic intracranial diseases (e.g., multiple sclerosis);
• Acute renal failure, current dialysis, or estimated glomerular filtration rate (eGFR)\<30ml/min/1.72m2, and/or serum creatinine\>220mmol/L (2.5mg/dl);
• History of severe liver disease, or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or glutamyl transferase (GGT) ≥3×upper limit of normal value (ULN) and/or total bilirubin (TBIL) ≥2×ULN;
• Severe non-cardiovascular comorbidity with an expected life expectancy of less than 3 months (e.g., malignant tumors);
• Known pregnancy or breastfeeding, or a positive pregnancy test prior to randomization;
• Current participation in another drug or device clinical trial;
• Any other condition deemed by the investigator to make the patient unsuitable for participation in the study or to pose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric illness, cognitive impairment, or emotional disorders).

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

RECRUITING

Related Publications (12)

• Rahme R, Abruzzo TA, Martin RH, Tomsick TA, Ringer AJ, Furlan AJ, Carrozzella JA, Khatri P. Is intra-arterial thrombolysis beneficial for M2 occlusions? Subgroup analysis of the PROACT-II trial. Stroke. 2013 Jan;44(1):240-2. doi: 10.1161/STROKEAHA.112.671495. Epub 2012 Dec 6.

  PMID: 23223507 RESULT

• Ospel JM, Menon BK, Demchuk AM, Almekhlafi MA, Kashani N, Mayank A, Fainardi E, Rubiera M, Khaw A, Shankar JJ, Dowlatshahi D, Puig J, Sohn SI, Ahn SH, Poppe A, Calleja A, Hill MD, Goyal M. Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment. Stroke. 2020 Nov;51(11):3232-3240. doi: 10.1161/STROKEAHA.120.030227. Epub 2020 Oct 19.

  PMID: 33070714 RESULT

• Howard G, Waller JL, Voeks JH, Howard VJ, Jauch EC, Lees KR, Nichols FT, Rahlfs VW, Hess DC. A simple, assumption-free, and clinically interpretable approach for analysis of modified Rankin outcomes. Stroke. 2012 Mar;43(3):664-9. doi: 10.1161/STROKEAHA.111.632935. Epub 2012 Feb 16.

  PMID: 22343650 RESULT

• Miao Z, Luo G, Song L, Sun D, Chen W, Yao X, Pan Y, Liu Y, Yuan G, Wen C, Wei M, Cai X, Yang Q, Zhou Z, Chang M, Nan G, Wang J, Xiang G, Zhou L, Gao W, Zhang H, Hao J, Xu C, Sun Y, Yi T, Feng G, Han H, Gao F, Ma N, Mo D, Sun X, Deng Y, Tong X, Li X, Jia B, Wang B, He Z, Yang M, Zhao X, Zhang X, Zhang L, Li S, Tong X, Jing J, Xiong Y, Liu T, Li Z, Ren Z, Wang Y, Liebeskind DS, Jovin TG, Nguyen TN, Wang Y, Liu L, Yan B, Huo X; ANGEL-TNK Investigators. Intra-arterial Tenecteplase for Acute Stroke After Successful Endovascular Therapy: The ANGEL-TNK Randomized Clinical Trial. JAMA. 2025 Aug 19;334(7):582-591. doi: 10.1001/jama.2025.10800.

  PMID: 40616323 RESULT

• Meng X, Li S, Dai H, Lu G, Wang W, Che F, Geng Y, Sun M, Li X, Li H, Wang Y. Tenecteplase vs Alteplase for Patients With Acute Ischemic Stroke: The ORIGINAL Randomized Clinical Trial. JAMA. 2024 Nov 5;332(17):1437-1445. doi: 10.1001/jama.2024.14721.

  PMID: 39264623 RESULT

• Ogawa A, Mori E, Minematsu K, Taki W, Takahashi A, Nemoto S, Miyamoto S, Sasaki M, Inoue T; MELT Japan Study Group. Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan. Stroke. 2007 Oct;38(10):2633-9. doi: 10.1161/STROKEAHA.107.488551. Epub 2007 Aug 16.

  PMID: 17702958 RESULT

• Goyal M, Ospel JM, Ganesh A, Dowlatshahi D, Volders D, Mohlenbruch MA, Jumaa MA, Nimjee SM, Booth TC, Buck BH, Kennedy J, Shankar JJ, Dorn F, Zhang L, Hametner C, Nardai S, Zafar A, Diprose W, Vatanpour S, Stebner A, Bosshart S, Singh N, Sebastian I, Uchida K, Ryckborst KJ, Fahed R, Hu SX, Vollherbst DF, Zaidi SF, Lee VH, Lynch J, Rempel JL, Teal R, Trivedi A, Bode FJ, Ogungbemi A, Pham M, Orosz P, Abdalkader M, Taschner C, Tarpley J, Poli S, Singh RJ, De Leacy R, Lopez G, Sahlas D, Chen M, Burns P, Schaafsma JD, Marigold R, Reich A, Amole A, Field TS, Swartz RH, Settecase F, Lenzser G, Ortega-Gutierrez S, Asdaghi N, Lobotesis K, Siddiqui AH, Berrouschot J, Mokin M, Ebersole K, Schneider H, Yoo AJ, Mandzia J, Klostranec J, Jadun C, Patankar T, Sauvageau E, Lenthall R, Peeling L, Huynh T, Budzik R, Lee SK, Makalanda L, Levitt MR, Perry RJ, Hlaing T, Jahromi BS, Singh P, Demchuk AM, Hill MD; ESCAPE-MeVO Investigators. Endovascular Treatment of Stroke Due to Medium-Vessel Occlusion. N Engl J Med. 2025 Apr 10;392(14):1385-1395. doi: 10.1056/NEJMoa2411668. Epub 2025 Feb 5.

  PMID: 39908448 RESULT

• Psychogios M, Brehm A, Ribo M, Rizzo F, Strbian D, Raty S, Arenillas JF, Martinez-Galdamez M, Hajdu SD, Michel P, Gralla J, Piechowiak EI, Kaiser DPO, Puetz V, Van den Bergh F, De Raedt S, Bellante F, Dusart A, Hellstern V, Khanafer A, Parrilla G, Morales A, Kirschke JS, Wunderlich S, Fiehler J, Thomalla G, Lemmens R, Peluso JP, Bolognese M, von Hessling A, van Es A, Kruyt ND, Coutinho JM, Castano C, Minnerup J, van Zwam W, Dhondt E, Nolte CH, Machi P, Loehr C, Mattle HP, Buhk JH, Kaesmacher J, Dobrocky T, Papanagiotou P, Alonso A, Holtmannspoetter M, Zini A, Renieri L, Keil F, van den Wijngaard I, Kagi G, Terceno M, Wiesmann M, Amaro S, Rommers N, Balmer L, Fragata I, Katan M, Leker RR, Saver JL, Staals J, Fischer U; DISTAL Investigators. Endovascular Treatment for Stroke Due to Occlusion of Medium or Distal Vessels. N Engl J Med. 2025 Apr 10;392(14):1374-1384. doi: 10.1056/NEJMoa2408954. Epub 2025 Feb 5.

  PMID: 39908430 RESULT

• Mohammaden MH, Souza Viana L, Abdelhamid H, Olive-Gadea M, Rodrigo-Gisbert M, Requena M, Martins PN, Matsoukas S, Schuldt BR, Fifi JT, Farooqui M, Vivanco-Suarez J, Ortega-Gutierrez S, Klein P, Abdalkader M, Vigilante N, Siegler JE, Moreira Ferreira F, Peng S, Alaraj A, Haussen DC, Nguyen TN, Nogueira RG. Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study. Stroke. 2024 Jun;55(6):1489-1497. doi: 10.1161/STROKEAHA.123.045228. Epub 2024 May 24.

  PMID: 38787927 RESULT

• Saber H, Desai SM, Haussen D, Al-Bayati A, Majidi S, Mocco J, Hassan AE, Rajah G, Waqas M, Davies JM, Dornbos D 3rd, Nickele C, Arthur AS, Mowla A, Tenser MS, Mokin M, Pressman E, Aghaebrahim A, Hanel RA, Ortega-Gutierrez S, Jovin T, Duckwiler GR, Liebeskind DS, Nogueira RG, Gornbein J, Saver JL, Jadhav AP. Endovascular Therapy vs Medical Management for Patients With Acute Stroke With Medium Vessel Occlusion in the Anterior Circulation. JAMA Netw Open. 2022 Oct 3;5(10):e2238154. doi: 10.1001/jamanetworkopen.2022.38154.

  PMID: 36279137 RESULT

• Guo Y, Wu H, Zhang TY, Li YP, Yang JC, Yang MF, Hu YQ, Zhang HZ. Endovascular treatment achieves better outcomes than best medical management in patients with M2 occlusion and high stroke severity: a meta-analysis. J Neurol. 2023 Jun;270(6):2924-2937. doi: 10.1007/s00415-023-11653-x. Epub 2023 Mar 2.

  PMID: 36862149 RESULT

• Duloquin G, Graber M, Garnier L, Crespy V, Comby PO, Baptiste L, Mohr S, Delpont B, Gueniat J, Blanc-Labarre C, Hervieu-Begue M, Osseby GV, Giroud M, Bejot Y. Incidence of Acute Ischemic Stroke With Visible Arterial Occlusion: A Population-Based Study (Dijon Stroke Registry). Stroke. 2020 Jul;51(7):2122-2130. doi: 10.1161/STROKEAHA.120.029949. Epub 2020 Jun 3.

  PMID: 32486967 RESULT

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Liping Liu

CONTACT

+86-010-59978328; lipingsister@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Since the experimental group needs to perform arterial thrombolysis and related operations on patients, the doctors and nurses involved in the study will not be blinded for random patient allocation. However, the grouping of patients will blind neurologists and nurses responsible for conducting neurological, imaging and functional evaluations at baseline and follow-up, as well as collecting clinical outcome data. The randomization information of the patients will also blind the members of the outcome assessment committee.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 11, 2026
• First Posted: January 22, 2026
• Study Start: January 22, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)