Intra-arterial Tenecteplase for Acute Medium Vessel Occlusion Stroke

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).

Timeline

Start

2026-01-22

Primary completion

2027-09-30

Completion

2027-12-31

Publications

• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.

Drugs

Indications