Neurology Clinical Trial Database
BRIDGE-TNK
Intravenous Tenecteplase before Thrombectomy in Stroke
Clinical Question
Does adding intravenous tenecteplase before thrombectomy improve functional independence at 90 days in patients with acute ischemic stroke due to large-vessel occlusion?
Bottom Line
Tenecteplase before thrombectomy improved functional independence at 90 days compared to thrombectomy alone.
Major Points
- First RCT to demonstrate superiority of IV tenecteplase bridging before thrombectomy over direct thrombectomy alone: 52.9% vs 44.1% achieved functional independence (mRS 0–2) at 90 days (RR 1.18, 95% CI 1.01–1.39, P=0.04).
- Directly addresses the direct-to-thrombectomy debate — contradicts DIRECT-MT, MR CLEAN-NO IV, and SWIFT DIRECT which suggested bridging with alteplase is unnecessary, by showing tenecteplase specifically adds benefit.
- Higher pre-thrombectomy reperfusion rate with tenecteplase (6.1% vs 1.1%) and faster puncture-to-reperfusion time (55 vs 64 min), suggesting TNK facilitates the thrombectomy procedure itself.
- No significant increase in symptomatic ICH (8.5% vs 6.7%, P=0.33) — safety profile acceptable despite additional thrombolytic exposure.
- NNT of 11 to achieve one additional functionally independent patient — a clinically compelling treatment effect for a simple IV bolus.
- Included posterior circulation occlusions (vertebrobasilar) — broader inclusion than most bridging trials, though subgroup data not separately reported.
- Used 0.25 mg/kg tenecteplase (max 25 mg) — the dose increasingly adopted worldwide based on EXTEND-IA TNK, AcT, and now BRIDGE-TNK.
- China-only enrollment (39 centers) — raises generalizability questions, though Chinese stroke populations overlap substantially with global LVO demographics.
- Mortality was similar (22.3% vs 19.9%, P=0.39) — the benefit was in shifting outcomes toward independence rather than reducing death.
- Together with AcT (2024) establishing TNK noninferiority to alteplase and BRIDGE-TNK showing bridging benefit, strongly supports tenecteplase as the optimal bridging agent before thrombectomy.
Design
Study Type: Randomized, open-label, blinded endpoint (PROBE)
Randomization: 1
Blinding: Outcome assessors blinded
Enrollment Period: May 2022 – September 2024
Follow-up Duration: 90 days
Centers: 39
Countries: China
Sample Size: 550
Analysis: Modified Poisson regression; intention-to-treat
Inclusion Criteria
- Age ≥18 years
- Large-vessel occlusion (ICA, M1, M2, or vertebrobasilar)
- Within 4.5 hours of last-known-well
- Eligible for thrombolysis per Chinese guidelines
Exclusion Criteria
- Standard contraindications to IV thrombolysis per Chinese guidelines
- Prior IV thrombolysis administered before screening
- Known allergy or hypersensitivity to tenecteplase
- Pre-stroke mRS ≥2 (significant pre-existing disability)
- Intracranial hemorrhage on baseline imaging
- ASPECTS <6 on baseline CT (large established infarct)
- Blood glucose <2.7 mmol/L or >22.2 mmol/L
- Pregnancy or breastfeeding
Arms
| Field | Tenecteplase + Thrombectomy | Control |
|---|---|---|
| Intervention | IV Tenecteplase (0.25 mg/kg, max 25 mg) then endovascular thrombectomy | Direct endovascular thrombectomy without IV thrombolysis |
| Duration | Single bolus + thrombectomy | Immediate thrombectomy |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Functional independence (mRS 0–2) at 90 days | Primary | 44.1% | 52.9% | 1.18 | 0.04 |
| Reperfusion before thrombectomy | Secondary | 1.1% | 6.1% | 5.19 | |
| Reperfusion after thrombectomy | Secondary | 94.1% | 91.4% | 0.97 | |
| Excellent outcome (mRS 0–1) | Secondary | 27.9% | 34.9% | 1.24 | |
| Death at 90 days | Secondary | 19.9% | 22.3% | 1.17 | 0.39 |
| Symptomatic ICH | Adverse | 6.7% | 8.5% | 0.33 | |
| Any ICH on imaging | Adverse | 32.3% | 31.0% |
Criticisms
- Open-label PROBE design — knowledge of treatment allocation could influence thrombectomy approach, procedural decisions, and post-procedural care.
- China-only enrollment (39 centers) — generalizability to non-Chinese populations, different healthcare systems, and longer transfer times is uncertain.
- Excluded inter-hospital transfers — cannot extrapolate to drip-and-ship scenarios where TNK would have the most time to work during transport.
- Absolute benefit (8.8% absolute difference) was smaller than the assumed 15% difference used for power calculation — the trial barely reached significance (P=0.04).
- Generalizability to the >4.5-hour window is uncertain — all patients were within 4.5 hours, leaving the extended-window bridging question unanswered.
- Contradicts prior bridging trials (DIRECT-MT, MR CLEAN-NO IV, SWIFT DIRECT) that used alteplase — the TNK-specific benefit may not extend to alteplase, complicating interpretation.
- sICH rate in TNK group (8.5%) was numerically higher than control (6.7%) — while not significant, a larger trial might reveal a true safety signal.
- No data on cost-effectiveness — adding TNK to a thrombectomy pathway may not be cost-effective given the marginal absolute benefit.
- Partially industry-funded (CSPC Pharmaceutical, a Chinese TNK manufacturer) — potential conflict of interest.
Funding
Chongqing Science and Health Joint Medical Research Project, National Natural Science Foundation of China, CSPC Pharmaceutical (Guangzhou)
Based on: BRIDGE-TNK (The New England Journal of Medicine, 2025)
Authors: Qiu Z, Li F, Sang H, ..., Xie D
Citation: Qiu Z, Li F, Sang H, et al. N Engl J Med. 2025 May 21. DOI:10.1056/NEJMoa2503867
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