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

NCT06987305 | Recruiting Phase 3 DMC

• 1 other identifier: BRIDGE-TNK EXTEND
• Study Type: interventional
• Target: 820
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Stroke, Acute Ischemic

Keywords

acute ischemic stroke; endovascular treatment; rhTNK-tPA

Outcome Measures

Primary Outcomes (1)

• Proportion of patients functionally independent (mRS score 0 to 2) at 90 days

  functional independence

  90 days post-randomization

Secondary Outcomes (9)

• Substantial reperfusion (defined as an eTICI grade of 2b, 2c, or 3) at initial angiogram

  within 5 minutes at initial angiogram

• Successful reperfusion (defined as an eTICI grade of 2b, 2c, or 3) at end-of-procedure angiography

  15 minutes after initial angiogram

• Modified first-pass reperfusion

  Perioperative (After artery puncture, but the start of procedure)

• First-pass reperfusion

  Perioperative (After artery puncture, but the start of procedure)

• Final infarct volume on day 1.5 MRI/CT

  1.5 days post-randomization

Study Arms (2)

rhTNK-tPA group

EXPERIMENTAL

Patients in this group will be treated with intravenous rhTNK-tPA and endovascular thrombectomy

Drug: Intravenous rhTNK-tPA; Procedure: Endovascular thrombectomy

Placebo group

PLACEBO COMPARATOR

Patients in this group will be treated with intravenous placebo and endovascular thrombectomy

Drug: Intravenous placebo; Procedure: Endovascular thrombectomy

Interventions

Intravenous rhTNK-tPA DRUG

Patients will received intravenous rhTNK-tPA

Also known as: Intravenous tenecteplase, Intravenous TNK

rhTNK-tPA group

Intravenous placebo DRUG

Patients will received intravenous placebo

Also known as: Intravenous placebo (a look-alike substance that contains no drug)

Placebo group

Endovascular thrombectomy PROCEDURE

Patients will received endovascular thrombectomy

Also known as: Endovascular treatment, Mechanical thrombectomy

Placebo group; rhTNK-tPA 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;
• Acute ischemic stroke presenting within 4.5-24 hours of last known well;
• No significant pre-stroke functional disability: for age \<80 years, pre-stroke modified Rankin scale (mRS) ≤2; for age ≥80 years, prestroke mRS ≤1;
• Baseline NIHSS score ≥5;
• Imaging criteria of BOTH:
• Occlusion on CTA/MRA in one of the following vessels: M1/M2 segment of middle cerebral artery, A1 segment of anterior cerebral artery, V4 segment of vertebral artery, basilar artery, or P1 segment of posterior cerebral artery. For A1, or P1 occlusions, vessel diameter must be ≥0.75 mm;
• For anterior circulation occlusion: CTP/MRP demonstrating mismatch ratio ≥1.8, absolute mismatch volume ≥15 mL, and ischemic core volume \<70 mL; OR have a mismatch between the presence of an abnormal signal on MRI diffusion-weighted imaging and no visible signal change on FLAIR. For posterior circulation occlusion: pc-ASPECTS score ≥6.
• Plan to received endovascular thrombectomy;
• The patient or their legal representative provides written informed consent.

You may not qualify if:

• Intracranial hemorrhage confirmed by CT/MRI;
• Already received intravenous thrombolytic after index stroke.;
• Pregnancy or lactation;
• Concurrent participation in other investigation drug clinical trials;
• Arterial tortuosity or other vascular anomalies precluding endovascular access to target vessel;
• Pre-existing neurological/psychiatric disorders interfering with neurological assessment;
• Space-occupying intracranial tumors (except small meningiomas ≤3 cm);
• Intracranial aneurysm or arteriovenous malformation;
• Terminal illness with life expectancy \<6 months;
• Anticipated inability to complete follow-up assessments.

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead
• China Shijiazhuang Pharmaceutical Company RECOMGEN PHARMACEUTICAL (GUANGZHOU) CO.,LTD: collaborator
• The First Affiliated Hospital of Nanchang University: collaborator

Study Sites (4)

Wuhan No. 1 Hospital

Wuhan, Hubei, 430000, China

RECRUITING

Xiangtan Central Hospital

Xiangtan, Hunan, 421001, China

RECRUITING

Jiujiang First People's Hospital

Jiujiang, Jiangxi, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

RECRUITING

Related Publications (2)

• 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.

  PMID: 38329148 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.

  PMID: 39654273 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

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

Study Officials

• Qingwu Yang, MD

  Department of Neurology, Xinqiao Hospital of the Army Medical University

  PRINCIPAL INVESTIGATOR

• Daojun Hong, MD

  The First Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhongming Qiu, MD

CONTACT

13236599269; qiuzhongmingdoctor@163.com

Jing Lin, MD

CONTACT

15626456674; linjingsys2016@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 23, 2025
• Study Start: October 21, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): February 29, 2028
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Related papers published 6 months later, the IPD will be shared
• Access Criteria: yangqwmlys@l63.com

Locations

CN (4)