Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke

Summary

The proposed trial is a pragmatic, registry linked, prospective, randomized (1:1) controlled, open-label parallel group clinical trial with blinded endpoint assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non-inferior to intravenous alteplase (0.9 mg/kg body weight) in patients with acute ischemic stroke otherwise eligible for intravenous thrombolysis as per standard care. All patients will have standard of care medical management on an acute stroke unit. There are no additional trial specific management recommendations. Patients will be followed for approximately 90-120 days.

Timeline

Start

2019-12-10

Primary completion

2022-04-26

Completion

2023-04-30

Publications

• Appoo A, Ignacio K, Doolan C, Bala F, Almekhlafi M, Buck BH, Tkach A, Catanese L, Swartz RH, Sajobi TT, Ganesh A, Menon BK, Singh N. Predictors and Consequences of Serious Adverse Events in Patients Treated With Thrombolysis: A Prespecified Secondary Analysis of the AcT Trial. J Am Heart Assoc. 2026 Jun 16;15(12):e048280. doi: 10.1161/JAHA.125.048280. Epub 2026 Jun 9.
• Ignacio KHD, Bala F, Catanese L, Tkach A, Kate M, Buck B, Ademola A, Sajobi TT, Field TS, Pikula A, Shamy M, Hunter G, Swartz RH, Horn M, Dowlatshahi D, Shankar JJ, Hill MD, Menon BK, Almekhlafi MA, Singh N. Comparing Clinical Characteristics and Outcomes of Tenecteplase Versus Alteplase in Young Adult Patients With Stroke: A Secondary Analysis of the AcT Trial. Stroke Vasc Interv Neurol. 2026 Jan 22;6(2):e001974. doi: 10.1161/SVIN.125.001974. eCollection 2026 Mar.
• Sujanthan S, Rajkumar G, Dainty KN, Barense M, Lanctot KL, Owen AM, Singh N, Buck BH, Khosravani H, Coutts SB, Almekhlafi M, Appireddy R, Tkach A, Catanese L, Dowlatshahi D, Mandzia J, Pikula A, Williams H, Field TS, Manosalva A, Siddiqui M, Hunter G, Horn M, Bala F, Hill MD, Shamy M, Ganesh A, Sajobi T, Menon BK, Swartz RH; AcT Trial Investigators. Faster Thrombolysis Is Associated With Improved Cognitive Outcomes in Patients With Acute Ischemic Stroke Treated With Alteplase and Tenecteplase: A Substudy of the AcT Trial. Stroke. 2025 Oct;56(10):2858-2865. doi: 10.1161/STROKEAHA.125.051670. Epub 2025 Jul 18.
• Singh N, Bala F, Ademola A, Almekhlafi M, Coutts SB, Deschaintre Y, Khosravani H, Buck BH, Appireddy R, Moreau F, Gubitz G, Tkach A, Catanese L, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar JJ, Poppe AY, Williams H, Field TS, Manosalva A, Siddiqui M, Zafar A, Imoukhoude O, Hunter G, Shamy M, Demchuk A, Swartz RH, Hill MD, Sajobi TT, Menon BK, Ganesh A. Safety, Functional Disability, Healthcare Utilization, and Quality-of-Life Outcomes in Elderly Receiving Alteplase and Tenecteplase: A Secondary Analysis From the AcT Trial. Stroke. 2025 May;56(5):1169-1179. doi: 10.1161/STROKEAHA.124.049512. Epub 2025 Mar 24.
• Bala F, Diprose W, Menon BK, Singh N, Khosravani H, Tkach A, Catanese L, Dowlatshahi D, Field TS, Hunter G, Sajobi T, Hill MD, Buck BH, Swartz RH, Almekhlafi MA. Effect of thrombolysis type on the efficacy of aspiration versus stent retriever first line thrombectomy: results from the AcT trial. J Neurointerv Surg. 2025 Jun 1;17(e2):e276-e280. doi: 10.1136/jnis-2024-022268.
• Sajobi TT, Arimoro OI, Ademola A, Singh N, Bala F, Almekhlafi MA, Deschaintre Y, Coutts SB, Thirunavukkarasu S, Khosravani H, Appireddy R, Moreau F, Gubitz GJ, Tkach A, Catanese L, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar JS, Williams H, Field TS, Manosalva A, Siddiqui M, Zafar A, Imoukhuede O, Hunter G, Demchuk AM, Mishra SM, Gioia LC, Jalini S, Cayer C, Phillips SJ, Elamin E, Shoamanesh A, Subramaniam S, Kate MP, Jacquin G, Camden MC, Benali F, Alhabli I, Horn M, Stotts G, Hill MD, Gladstone DJ, Poppe AY, Sehgal A, Zhang Q, Lethebe B, Doram C, Shamy M, Kenney C, Buck BH, Swartz RH, Menon BK. Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial. Stroke. 2024 Mar;55(3):524-531. doi: 10.1161/STROKEAHA.123.044690. Epub 2024 Jan 26.
• Kim DJ, Singh N, Catanese L, Yu AYX, Demchuk AM, Lloret-Villas MI, Deschaintre Y, Coutts SB, Khosravani H, Appireddy R, Moreau F, Gubitz G, Tkach A, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar J, Williams H, Manosalva H, Siddiqui M, Zafar A, Imoukhuede O, Hunter G, Phillips S, Hill MD, Poppe AY, Ademola A, Shamy M, Bala F, Sajobi TT, Swartz RH, Almekhlafi MA, Menon BK, Field TS. Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase. Stroke. 2024 Feb;55(2):288-295. doi: 10.1161/STROKEAHA.123.045320. Epub 2024 Jan 4.
• Singh N, Almekhlafi MA, Bala F, Ademola A, Coutts SB, Deschaintre Y, Khosravani H, Buck B, Appireddy R, Moreau F, Gubitz G, Tkach A, Catanese L, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar JJ, Ghrooda E, Poppe AY, Williams H, Field TS, Manosalva A, Siddiqui MM, Zafar A, Imoukhoude O, Hunter G, Shamy M, Demchuk AM, Claggett BL, Hill MD, Sajobi TT, Swartz RH, Menon BK. Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial. Stroke. 2023 Nov;54(11):2766-2775. doi: 10.1161/STROKEAHA.123.044267. Epub 2023 Oct 6.
• Menon BK, Buck BH, Singh N, Deschaintre Y, Almekhlafi MA, Coutts SB, Thirunavukkarasu S, Khosravani H, Appireddy R, Moreau F, Gubitz G, Tkach A, Catanese L, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar J, Williams H, Field TS, Manosalva A, Siddiqui M, Zafar A, Imoukhuede O, Hunter G, Demchuk AM, Mishra S, Gioia LC, Jalini S, Cayer C, Phillips S, Elamin E, Shoamanesh A, Subramaniam S, Kate M, Jacquin G, Camden MC, Benali F, Alhabli I, Bala F, Horn M, Stotts G, Hill MD, Gladstone DJ, Poppe A, Sehgal A, Zhang Q, Lethebe BC, Doram C, Ademola A, Shamy M, Kenney C, Sajobi TT, Swartz RH; AcT Trial Investigators. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022 Jul 16;400(10347):161-169. doi: 10.1016/S0140-6736(22)01054-6. Epub 2022 Jun 29.

Drugs

Indications