TRACE-5
(2026)Objective
To assess whether intravenous tenecteplase administered within 24 hours of symptom onset improves functional outcome compared with standard medical treatment in patients with basilar artery occlusion.
Study Summary
• Symptomatic ICH was low and similar between groups (2% vs 3%) with no increase in 90-day mortality (29% vs 31%)
• Benefit was consistent across subgroups including patients not receiving thrombectomy and those in the 6–24 h window
Intervention
Tenecteplase 0.25 mg/kg IV bolus (max 25 mg) within 24 hours vs standard medical treatment (could include IV alteplase 0.9 mg/kg within 4.5 h, anticoagulation, or antiplatelets), with or without endovascular thrombectomy
Inclusion Criteria
Age ≥18 years, ischaemic stroke due to basilar artery occlusion (near or complete on CTA/MRA), eligible for IV thrombolytics within 24 h of onset or last known well, pre-stroke mRS ≤3, no NIHSS restriction
Study Design
Arms: Tenecteplase group vs Standard medical treatment group
Patients per Arm: 221 tenecteplase, 231 standard medical treatment
Outcome
• Ordinal mRS shift analysis also significant (adjusted common OR 1.51, 95% CI 1.06–2.15; p=0.022)
• Symptomatic ICH within 36 h: 2% vs 3% (adjusted RR 0.58, 95% CI 0.17–1.99); 90-day mortality: 29% vs 31% (adjusted RR 0.87, 95% CI 0.62–1.22)
Bottom Line
Tenecteplase within 24 hours significantly improved the rate of excellent functional outcome (mRS 0–1) in basilar artery occlusion (38% vs 29%; adjusted RR 1.50, p=0.014) without increasing symptomatic ICH or mortality. This is the first phase 3 RCT supporting extended-window thrombolysis specifically for confirmed basilar artery occlusion, with benefit preserved regardless of thrombectomy use, and without requiring advanced perfusion imaging for patient selection.
Major Points
- First phase 3 RCT demonstrating benefit of tenecteplase up to 24 hours specifically in confirmed basilar artery occlusion
- Primary outcome (mRS 0–1 or return to baseline at 90 days): 38% tenecteplase vs 29% standard treatment (adjusted RR 1.50, 95% CI 1.09–2.08; p=0.014)
- Ordinal mRS shift analysis was also significant (adjusted common OR 1.51, 95% CI 1.06–2.15; p=0.022)
- Substantial pre-thrombectomy reperfusion (eTICI 2B–3) was significantly higher with tenecteplase: 24% vs 13% (adjusted RR 1.90, 95% CI 1.04–3.49; p=0.038)
- Symptomatic ICH within 36 hours was low and similar: 2% vs 3% (adjusted RR 0.58, 95% CI 0.17–1.99)
- 90-day mortality was similar: 29% vs 31% (adjusted RR 0.87, 95% CI 0.62–1.22), reflecting the severity of basilar artery occlusion
- 49% of patients underwent endovascular thrombectomy; 35% of controls received alteplase within 4.5 h
- Subgroup analyses showed consistent benefit across age, sex, NIHSS severity, pc-ASPECTS, occlusion site, time windows, TOAST classification, and thrombectomy status
- Notably significant benefit in the 6–24 h time window subgroup (adjusted RR 2.51, 95% CI 1.40–4.50) and in patients not undergoing thrombectomy (adjusted RR 1.63, 95% CI 1.04–2.54)
- Pragmatic design used non-contrast CT/CTA or DWI without advanced perfusion imaging — facilitates implementation in resource-limited settings
- Single-bolus tenecteplase administration offers practical advantage over 1-hour alteplase infusion
- Predominantly atherothrombotic mechanism (84%) reflecting Chinese population with high intracranial atherosclerosis prevalence
Study Design
- Study Type
- Multicentre, prospective, randomised, open-label, blinded-endpoint (PROBE), superiority, phase 3 trial
- Randomization
- Yes
- Blinding
- Open-label with blinded endpoint assessment (PROBE design). Outcome assessors and the Endpoint Adjudication Committee were masked to treatment allocation. Randomisation used Central Interactive Management System with computerised allocation sequences.
- Sample Size
- 452
- Follow-up
- 90 days
- Centers
- 66
- Countries
- China
Primary Outcome
Definition: Proportion of participants with mRS score 0–1 or return to baseline mRS score (if pre-stroke mRS was 2–3) at 90 days
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 66/231 (29%) | 83/221 (38%) | - (Adjusted RR 1.50 (95% CI 1.09–2.08)) | p=0.014 |
Limitations & Criticisms
- Open-label design, though mitigated by blinded endpoint assessment (PROBE) and masked adjudication committee
- Conducted entirely in Chinese patients with high prevalence of intracranial atherosclerosis (84% atherothrombotic mechanism) — generalisability to other ethnicities with different stroke mechanisms (e.g., cardioembolic-predominant populations) is uncertain
- Heterogeneous control arm: 35% received alteplase, others received anticoagulation or antiplatelets only, complicating interpretation of the comparator
- 49% of patients underwent thrombectomy in both groups, making it difficult to isolate the independent effect of tenecteplase from combined thrombolysis + thrombectomy
- Patients with large established posterior circulation infarcts (pc-ASPECTS <6) were excluded, limiting generalisability to those with extensive ischaemia
- High mortality in both groups (~30%) reflects disease severity but means a large proportion of patients did not contribute to the functional outcome assessment
- No lower limit on NIHSS resulted in lower baseline severity (median NIHSS 12) than prior basilar artery thrombectomy trials (BAOCHE, ATTENTION), potentially enriching for milder strokes
- 9% protocol non-adherence rate including crossovers and alteplase use beyond 4.5 h window, though per-protocol results were consistent
- Tenecteplase formulation used was the same as TRACE-2 (Chinese manufacture); formal comparability data with internationally available formulations have not been published
- mRS 0–2 and mRS 0–3 secondary endpoints did not reach significance, suggesting benefit was concentrated at the excellent outcome end of the disability spectrum
- Secondary outcomes and subgroup analyses were not adjusted for multiple testing
- Median thrombolytic-to-arterial puncture time was 45 min, longer than some trials (e.g., 15 min in TIMELESS), which may have allowed more time for tenecteplase to achieve reperfusion
Citation
Lancet 2026; available online February 5, 2026