TRACE-2 Trial: Tenecteplase vs Alteplase in EVT-Ineligible Stroke
In patients with acute ischemic stroke within 4.5 hours who are ineligible for or refusing endovascular thrombectomy, is IV tenecteplase 0.25 mg/kg non-inferior to IV alteplase 0.9 mg/kg for excellent functional outcome (mRS 0-1) at 90 days?
Wang Y, et al. (Lancet 2023) · 1430 patients
Population
Included
- Acute ischemic stroke within 4.5 hours of onset
- Eligible for standard IV thrombolysis
- Ineligible for or refusing EVT
- NIHSS 5-25 at enrollment
- Premorbid mRS ≤1
- Adults aged at least 18 years
- Acute ischemic stroke eligible for standard intravenous thrombolytic treatment, able to receive treatment within 4.5 hours of stroke onset
- Ineligible for or refused endovascular thrombectomy
- Modified Rankin scale score of no more than 1 before enrollment
- Disabling ischemic stroke with a National Institutes of Health Stroke Scale score of 5 to 25
- Eligibility for thrombolytic treatment based on the Chinese Stroke Association guidelines, consistent with US and European national guidelines
Excluded
- Eligible for and agreeing to endovascular thrombectomy
- NIHSS <5 or >25
- Premorbid disability (mRS >1)
- Contraindication to IV thrombolysis
- Had received or intended to proceed to endovascular thrombectomy
- Contraindication to intravenous thrombolysis per guideline recommendations
Source: Wang Y et al., Lancet 2023· Retrieved 2026-06-09
Primary Outcome
Small absolute difference — interpret with caution
mRS 0-1 at 90 Days
Study Arms
- Agent
- Tenecteplase
- Dose
- 0.25 mg/kg (max 25 mg)
- Route
- IV
- Frequency
- Single bolus
- Duration
- One-time
Standard-window thrombolysis in patients eligible for IV thrombolytic but ineligible for or refusing thrombectomy. Non-inferiority margin was 0.937 for the risk ratio.
- Agent
- Alteplase
- Dose
- 0.9 mg/kg (max 90 mg)
- Route
- IV
- Frequency
- 10% as initial bolus, then remainder over a 1-h infusion
- Duration
- 60 minutes
Safety
Symptomatic intracranial hemorrhage within 36 hours
2%
2%
sICH was identical between arms (2% each, RR 1.18, 95% CI 0.56-2.50). Mortality was 7% tenecteplase vs 5% alteplase (RR 1.31, CI 0.86-2.01, not significant).
Trial Design
Type
- Phase 3, multicenter, open-label, blinded-endpoint noninferiority trial
- Standard-window IVT in EVT-ineligible or EVT-refusing stroke
- Tenecteplase 0.25 mg/kg vs alteplase
Timeline
China; June 2021 to May 2022
N
1430
Enrollment
1,430 patients at 53 centres in China. Phase 3 open-label blinded-endpoint NI RCT. June 2021 to May 2022. Published Lancet 2023.
ClinicalTrials.gov
NCT04797013Bedside Pearl
TRACE-2 is a major validation of tenecteplase 0.25 mg/kg for standard-window IVT in EVT-ineligible patients (NI confirmed, RR 1.07, sICH 2% each). Together with AcT and ATTEST-2, TRACE-2 provides the evidence base for the 2026 guideline endorsement of tenecteplase as an acceptable alternative to alteplase. Single-bolus administration simplifies door-to-needle workflows.