Intravenous rhTNK-tPA Before Stroke Thrombectomy in the Extended Time Window

Summary

This randomized, double-blind, placebo-controlled phase III clinical trial aims to evaluate the efficacy and safety of intravenous recombinant human tenecteplase (rhTNK-tPA) in acute ischemic stroke patients with large vessel occlusion presenting 4.5-24 hours after last known well. The study will address two primary questions: 1) Whether rhTNK-tPA enhances pre-thrombectomy reperfusion rates and improves 90-day functional outcomes compared to placebo; 2) Whether rhTNK-tPA increases the risk of symptomatic intracranial hemorrhage and mortality. Participants will be randomized to receive either a single bolus of rhTNK-tPA (0.25 mg/kg, max 25 mg) or matching placebo administered intravenously over 5 seconds. Key assessments include repeat neuroimaging (CT/CTA or MRI/MRA) at 24 hours post-treatment to evaluate reperfusion, NIH Stroke Scale score at day 5-7, and modified Rankin Scale score assessment at 90 days. Safety monitoring will focus on hemorrhagic transformation and mortality events throughout the study period.

Timeline

Start

2025-10-21

Primary completion

2027-10-31

Completion

2028-02-29

Publications

• Background Albers GW, Jumaa M, Purdon B, Zaidi SF, Streib C, Shuaib A, Sangha N, Kim M, Froehler MT, Schwartz NE, Clark WM, Kircher CE, Yang M, Massaro L, Lu XY, Rippon GA, Broderick JP, Butcher K, Lansberg MG, Liebeskind DS, Nouh A, Schwamm LH, Campbell BCV; TIMELESS Investigators. Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection. N Engl J Med. 2024 Feb 22;390(8):701-711. doi: 10.1056/NEJMoa2310392. Epub 2024 Feb 8.
• Background Yogendrakumar V, Campbell BC, Churilov L, Garcia-Esperon C, Choi PM, Cordato DJ, Guha P, Sharma G, Chen C, McDonald A, Thijs V, Mamun A, Dos Santos A, Balabanski AH, Kleinig TJ, Butcher KS, Devlin MJ, O'Rourke F, Donnan GA, Davis SM, Levi CR, Ma H, Parsons MW. Extending the time window for tenecteplase by effective reperfusion of penumbral tissue in patients with large vessel occlusion: Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 trial. Int J Stroke. 2025 Mar;20(3):367-372. doi: 10.1177/17474930241308660. Epub 2024 Dec 31.

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Indications