IV tenecteplase given before clot removal for large-vessel ischemic stroke in the 4.5–24 hour window

Intravenous rhTNK-tPA Versus Placebo Before Endovascular Thrombectomy For Stroke Patient With Large Vessel Occlusion In The Extended Time Window: the BRIDGE-TNK EXTEND Randomized, Placebo-controlled, Double-blind Trial

This trial tests whether a single IV dose of tenecteplase given before clot removal helps people with large-vessel ischemic stroke who arrive 4.5–24 hours after they were last well.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 820 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Xinqiao Hospital of Chongqing (Academic / other)
• Locations: 4 sites (Wuhan, Hubei and 3 other locations)
• Trial ID: NCT06987305 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled Phase 3 trial randomizes adults with confirmed large-vessel occlusion and salvageable brain tissue to a single weight-adjusted IV bolus of rhTNK-tPA or matching placebo prior to endovascular thrombectomy. Key imaging selection uses CTA/MRA plus perfusion mismatch (or DWI-FLAIR criteria) to identify patients with core <70 mL and salvageable tissue; posterior circulation cases require pc-ASPECTS ≥6. Primary outcome is functional independence (mRS 0–2) at 90 days, with coprimary and secondary mechanistic endpoints including pre-thrombectomy reperfusion, first-pass reperfusion, and early infarct volume; safety outcomes focus on symptomatic intracranial hemorrhage and 90-day mortality. The trial uses centralized blinded outcome assessment, independent event adjudication and a data safety monitoring board and plans ~820 participants for adequate power.

Who should consider this trial

Good fit: Adults with acute ischemic stroke due to a large-vessel occlusion presenting 4.5–24 hours after last known well who have salvageable brain tissue on perfusion or MRI selection and are planned for endovascular thrombectomy are the intended participants.

Not a fit: Patients with large established infarct cores (>70 mL), contraindications to thrombolysis, without large-vessel occlusion, or presenting outside the 4.5–24 hour window are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, giving tenecteplase before thrombectomy could increase early reperfusion and improve the chance of functional independence at 90 days.

How similar studies have performed: Previous trials of tenecteplase before thrombectomy have shown promising improvements in pre-thrombectomy reperfusion and outcomes versus alteplase, but use specifically in the 4.5–24 hour extended window remains less well studied.

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.

Where this trial is running

Wuhan, Hubei and 3 other locations

• Wuhan No. 1 Hospital — Wuhan, Hubei, China (Recruiting)
• Xiangtan Central Hospital — Xiangtan, Hunan, China (Recruiting)
• Jiujiang First People's Hospital — Jiujiang, Jiangxi, China (Recruiting)
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Recruiting)

Study contacts

• Principal investigator: Qingwu Yang, MD — Department of Neurology, Xinqiao Hospital of the Army Medical University
• Study coordinator: Zhongming Qiu, MD

Conditions Stroke, Acute Ischemic; acute ischemic stroke; endovascular treatment; rhTNK-tPA