BRIDGE-TNK ASPECTS
(2026)Objective
Test whether baseline ASPECTS modifies the efficacy and safety of IV tenecteplase administered before endovascular thrombectomy in large-vessel-occlusion stroke.
Study Summary
• ASPECTS <8 (n=241): 90-day functional independence 41.6% with TNK+EVT vs 25.0% with EVT alone (aRR 1.67, 95% CI 1.18–2.35, p=0.003), no excess sICH (10.0% vs 11.2%) or mortality (29.2% vs 30.5%).
• ASPECTS 8–10 (n=309): no functional benefit (60.6% vs 61.1%; aRR 0.99, 95% CI 0.84–1.17) with numerically higher sICH (7.5% vs 2.8%) and higher 90-day mortality (17.6% vs 10.4%; aRR 1.89, 95% CI 0.99–3.61, p‑interaction = 0.04).
Intervention
IV tenecteplase 0.25 mg/kg (max 25 mg) before endovascular thrombectomy
Inclusion Criteria
Acute large-vessel occlusion stroke eligible for IV thrombolysis, within 4.5 hours of last known well, and scheduled for EVT
Study Design
Arms: Tenecteplase plus thrombectomy vs thrombectomy alone, stratified by baseline ASPECTS (<8 vs 8–10)
Patients per Arm: TNK+EVT 278 vs EVT alone 272 (ASPECTS <8: 113 vs 128; ASPECTS 8–10: 165 vs 144)
Outcome
• sICH (48 h): 10.0% vs 11.2% in ASPECTS <8; 7.5% vs 2.8% in ASPECTS 8–10 (p‑interaction 0.11).
• 90-day mortality: 29.2% vs 30.5% in ASPECTS <8; 17.6% vs 10.4% in ASPECTS 8–10 (aRR 1.89, 95% CI 0.99–3.61, p‑interaction 0.04).
Clinical Question
In patients with acute large-vessel-occlusion ischemic stroke treated within 4.5 hours of last known well, does baseline ASPECTS (<8 vs 8–10) modify the efficacy and safety of IV tenecteplase administered before endovascular thrombectomy?
Bottom Line
IV tenecteplase before thrombectomy significantly improved 90-day functional independence only in patients with ASPECTS <8 (aRR 1.67), with no benefit and numerically higher sICH and mortality in patients with ASPECTS 8–10 (p‑interaction 0.007).
Major Points
- Post hoc, stratified subgroup analysis of the 550-patient BRIDGE-TNK randomized trial (39 Chinese centers, May 2022–September 2024) using a data-driven ASPECTS cutoff of <8 vs 8–10.
- ASPECTS <8 (n=241): 90-day mRS 0–2 was 41.6% with tenecteplase+thrombectomy vs 25.0% with thrombectomy alone (aRR 1.67, 95% CI 1.18–2.35, p=0.003); sICH 10.0% vs 11.2%; 90-day mortality 29.2% vs 30.5%.
- ASPECTS 8–10 (n=309): 90-day mRS 0–2 was 60.6% vs 61.1% (aRR 0.99, 95% CI 0.84–1.17, p=0.92); sICH numerically higher (7.5% vs 2.8%); 90-day mortality 17.6% vs 10.4% (aRR 1.89, 95% CI 0.99–3.61).
- Significant treatment-by-ASPECTS interactions for the primary outcome (p‑interaction 0.007) and 90-day mortality (p‑interaction 0.04); crossover point for functional independence at ASPECTS 9.
- Pre-EVT successful reperfusion was numerically higher with tenecteplase in both strata (ASPECTS <8: 6.2% vs 1.6%; ASPECTS 8–10: 6.1% vs 0.7%).
- Propensity-score-matched analyses (180 in ASPECTS <8, 220 in ASPECTS 8–10) confirmed the primary interaction pattern.
- Sensitivity analysis restricted to anterior-circulation occlusions with NCCT-based ASPECTS reproduced the interaction (p‑interaction 0.02).
- In the ASPECTS 0–5 subset (n≈72), tenecteplase yielded numerically higher mRS 0–2 (27.3% vs 11.1%) and significantly higher mRS 0–1 (18.2% vs 2.2%); no patient with ASPECTS 0–2 achieved functional independence.
Study Design
- Study Type
- Post hoc subgroup analysis of a randomized controlled trial
- Randomization
- Yes
- Blinding
- Open-label with blinded outcome assessment (parent trial)
- Sample Size
- 550
- Follow-up
- 90 days
- Centers
- 39
- Countries
- China
Primary Outcome
Definition: Proportion with functional independence (mRS 0-2) at 90 days, stratified by baseline ASPECTS (<8 vs 8-10) with treatment-by-ASPECTS interaction
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - | - | - | - |
Limitations & Criticisms
- Post hoc subgroup analysis; the <8 vs 8-10 ASPECTS cutoff was data-driven and not prespecified.
- Multiple comparisons unadjusted for multiplicity; findings are exploratory and hypothesis-generating.
- Parent trial was open-label; only outcome adjudication was blinded.
- Imaging heterogeneity across NCCT, DWI, and pc-ASPECTS may introduce measurement variability despite core-lab review.
- CT perfusion and quantitative NCCT hypodensity volumetry not routinely available within 4.5 hours, limiting characterization of ischemic core volume.
- Clot length, a potential IVT-response modifier, was not measured.
- Enrolled exclusively in China, limiting generalizability to other ethnic populations.
- Numerically higher sICH and mortality in the ASPECTS 8-10 tenecteplase group raise a safety signal requiring confirmation.
Citation
Neurology 2026;107(6):e218467. DOI: 10.1212/WNL.0000000000218467