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

NCT ID: NCT06987305

Last Updated: 2025-12-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 820 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-21
• Study Completion Date: 2028-02-29

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.

Detailed Description

This multicenter, phase III trial employs a randomized, double-blind, placebo-controlled design to investigate the therapeutic window extension for rhTNK-tPA in large vessel occlusion stroke. Eligible participants are adults with large vessel occlusion confirmed by vascular imaging (CTA/MRA), and salvageable brain tissue demonstrated by perfusion imaging (CTP/MRP) mismatch. Exclusion criteria include contraindications to thrombolysis, and large core infarction (>70 mL on CTP).

Patients will be randomized 1:1 to receive either weight-adjusted rhTNK-tPA (0.25 mg/kg) or placebo. All participants will undergo endovascular thrombectomy.

The primary outcome is functional independence (mRS 0-2) at 90 days. Secondary outcomes include substantial reperfusion at initial angiogram, first-pass reperfusion, final infarct volume on day 1.5 MRI/CT, etc. Safety outcomes include symptomatic intracranial hemorrhage per Heidelberg Bleeding Classification criteria within 36 hours, and 90-day mortality.

Safety monitoring includes independent adjudication of hemorrhagic events and all-cause mortality. A sample size of 820 participants provides 80% power to detect a 10% absolute difference in functional independence (α=0.05).

The trial incorporates centralized blinded outcome assessment and intention-to-treat analysis, with data oversight by an independent clinical events committee and data safety monitoring board.

Conditions

Stroke, Acute Ischemic

Keywords

acute ischemic stroke; endovascular treatment; rhTNK-tPA

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

rhTNK-tPA group

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

Group Type: EXPERIMENTAL

Intravenous rhTNK-tPA

Intervention Type: DRUG

Patients will received intravenous rhTNK-tPA

Endovascular thrombectomy

Intervention Type: PROCEDURE

Patients will received endovascular thrombectomy

Placebo group

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

Group Type: PLACEBO_COMPARATOR

Intravenous placebo

Intervention Type: DRUG

Patients will received intravenous placebo

Endovascular thrombectomy

Intervention Type: PROCEDURE

Patients will received endovascular thrombectomy

Interventions

Intravenous rhTNK-tPA

Patients will received intravenous rhTNK-tPA

Intervention Type: DRUG

Intravenous placebo

Patients will received intravenous placebo

Intervention Type: DRUG

Endovascular thrombectomy

Patients will received endovascular thrombectomy

Intervention Type: PROCEDURE

Other Intervention Names

Intravenous tenecteplase; Intravenous TNK; Intravenous placebo (a look-alike substance that contains no drug); Endovascular treatment; Mechanical thrombectomy

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years;

2. Acute ischemic stroke presenting within 4.5-24 hours of last known well;

3. No significant pre-stroke functional disability: for age <80 years, pre-stroke modified Rankin scale (mRS) ≤2; for age ≥80 years, prestroke mRS ≤1;

4. Baseline NIHSS score ≥5;

5. Imaging criteria of BOTH:

1. 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;

2. 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.

6. Plan to received endovascular thrombectomy;

7. The patient or their legal representative provides written informed consent.

Exclusion Criteria

1. Intracranial hemorrhage confirmed by CT/MRI;

2. Already received intravenous thrombolytic after index stroke.;

3. Pregnancy or lactation;

4. Concurrent participation in other investigation drug clinical trials;

5. Arterial tortuosity or other vascular anomalies precluding endovascular access to target vessel;

6. Pre-existing neurological/psychiatric disorders interfering with neurological assessment;

7. Space-occupying intracranial tumors (except small meningiomas ≤3 cm);

8. Intracranial aneurysm or arteriovenous malformation;

9. Terminal illness with life expectancy <6 months;

10. Anticipated inability to complete follow-up assessments.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

China Shijiazhuang Pharmaceutical Company RECOMGEN PHARMACEUTICAL (GUANGZHOU) CO.,LTD

UNKNOWN

Sponsor Role: collaborator

Xinqiao Hospital of Chongqing

OTHER

Sponsor Role: lead

Responsible Party

Zhongming Qiu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qingwu Yang, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Xinqiao Hospital of the Army Medical University

Daojun Hong, MD

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Nanchang University

Locations

Wuhan No. 1 Hospital

Wuhan, Hubei, China

Site Status: RECRUITING

Xiangtan Central Hospital

Xiangtan, Hunan, China

Site Status: RECRUITING

Jiujiang First People's Hospital

Jiujiang, Jiangxi, China

Site Status: RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhongming Qiu, MD

Role: CONTACT

Phone: 13236599269

Email: qiuzhongmingdoctor@163.com

Jing Lin, MD

Role: CONTACT

Phone: 15626456674

Email: linjingsys2016@126.com

Facility Contacts

Wenhua Liu, MD

Role: primary

Guangxiong Yuan

Role: primary

Tuanyuan Zheng, MD

Role: primary

Daojun Hong

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 38329148 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 39654273 (View on PubMed)

Other Identifiers

BRIDGE-TNK EXTEND

Identifier Type: -

Identifier Source: org_study_id