BRIDGE-TNK
(2025)Objective
To determine whether intravenous tenecteplase before endovascular thrombectomy improves functional independence compared to thrombectomy alone in acute ischemic stroke due to large-vessel occlusion.
Study Summary
• Functional independence at 90 days was higher with tenecteplase + thrombectomy.
• Early reperfusion occurred more frequently in the tenecteplase group.
• Early reperfusion occurred more frequently in the tenecteplase group.
Intervention
Participants received either intravenous tenecteplase (0.25 mg/kg, max 25 mg) followed by thrombectomy, or thrombectomy alone. All patients presented within 4.5 hours of stroke onset.
Inclusion Criteria
Adults with acute ischemic stroke due to large-vessel occlusion within 4.5 hours of onset, eligible for IV thrombolysis.
Study Design
Arms: Tenecteplase + Thrombectomy vs. Thrombectomy Alone
Patients per Arm: Tenecteplase: 278, Thrombectomy Alone: 272
Outcome
• Functional Independence (mRS 0–2): 52.9% (tenecteplase) vs. 44.1% (control); RR 1.18; P=0.04.
• Reperfusion Before Thrombectomy: 6.1% vs. 1.1%.
• Symptomatic ICH: 8.5% vs. 6.7%.
• Mortality at 90 days: 22.3% vs. 19.9%.
• Reperfusion Before Thrombectomy: 6.1% vs. 1.1%.
• Symptomatic ICH: 8.5% vs. 6.7%.
• Mortality at 90 days: 22.3% vs. 19.9%.
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.
Study Design
- Study Type
- Randomized, open-label, blinded endpoint (PROBE)
- Randomization
- Yes
- Blinding
- Outcome assessors blinded
- Sample Size
- 550
- Follow-up
- 90 days
- Centers
- 39
- Countries
- China
Primary Outcome
Definition: Functional independence (mRS 0–2) at 90 days
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 44.1% | 52.9% | 1.18 (1.01–1.39) | 0.04 |
Limitations & 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.
Citation
Qiu Z, Li F, Sang H, et al. N Engl J Med. 2025 May 21. DOI:10.1056/NEJMoa2503867