TRACE-III Trial: Tenecteplase for Ischemic Stroke 4.5-24 Hours Without Thrombectomy
In patients with ICA or MCA occlusion presenting 4.5 to 24 hours from last known well (including wake-up and unwitnessed stroke) with salvageable tissue on perfusion imaging and no access to endovascular thrombectomy, does IV tenecteplase 0.25 mg/kg improve excellent functional outcome (mRS 0-1) at 90 days compared with standard medical treatment?
Xiong et al. (NEJM 2024) · 516 patients
Population
Included
- ICA or MCA occlusion confirmed on vascular imaging
- Salvageable tissue on perfusion imaging (mismatch criteria)
- 4.5 to 24 hours from last known well (including wake-up and unwitnessed stroke)
- No access to or not proceeding with endovascular thrombectomy
- Aged 18 years or older
- Ischemic stroke, including stroke on awakening and unwitnessed stroke, recruited within 4.5 to 24 hours after the time last known to be well
- Prestroke modified Rankin scale score of 0 or 1
- National Institutes of Health Stroke Scale score of 6 to 25
- Occlusion of the intracranial internal carotid artery or the first (M1) or second (M2) segment of the middle cerebral artery on CT angiography or MR angiography
- Salvageable brain tissue on perfusion imaging using iStroke software, defined as ischemic core volume less than 70 mL, a ratio of hypoperfused tissue to ischemic core volume of at least 1.8, and a mismatch volume of at least 15 mL
Excluded
- Access to and agreement to endovascular thrombectomy
- Large established infarct core (no mismatch on perfusion imaging)
- Contraindication to IV thrombolysis
- Prior stroke with significant disability (mRS >1)
- Endovascular thrombectomy planned at the time of randomization
- Guideline-based contraindications to thrombolytic agents
Source: Xiong Y et al., NEJM 2024· Retrieved 2026-06-09
Primary Outcome
mRS 0-1 at 90 Days
Study Arms
- Agent
- Tenecteplase
- Dose
- 0.25 mg/kg (max 25 mg)
- Route
- IV
- Frequency
- Single bolus over 5 to 10 seconds
- Duration
- One-time
Late-window thrombolysis 4.5 to 24 hours after last known well in large-vessel occlusion with salvageable tissue on perfusion imaging, in patients without access to thrombectomy. This is not a bridging-before-EVT trial.
- Agent
- Antiplatelet therapy at investigator discretion
- Route
- Per standard care
- Co-interventions
- Standard medical treatment conforming to the 2018 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke
No routine thrombolysis or thrombectomy. Rescue thrombectomy after randomization was permitted at the treating clinician discretion if the patient deteriorated and thrombectomy became accessible; fewer than 2% of patients overall underwent rescue thrombectomy.
Safety
Symptomatic intracranial hemorrhage within 36 hours
3%
0.8%
sICH was higher with tenecteplase (3.0% vs 0.8%), a tradeoff to weigh against the 8.8 pp efficacy gain. Mortality was similar (13.3% vs 13.1%).
Trial Design
Type
- Multicenter randomized controlled trial
- Conducted in China
- Perfusion imaging selection
- 1:1 allocation (Tenecteplase vs. Standard treatment)
Timeline
Published 2024
N
516
Enrollment
516 patients at multiple centres in China. Multicenter RCT with perfusion-imaging selection. 4.5–24 hour enrollment window. Published NEJM 2024.
ClinicalTrials.gov
NCT05141305Bedside Pearl
TRACE-III is the key trial for late-window IVT when EVT cannot be performed. In perfusion-selected LVO patients 4.5-24 hours from onset without EVT access, tenecteplase 0.25 mg/kg improved mRS 0-1 from 24.2% to 33.0% (NNT 11, P=0.03). This is not a reason to delay EVT when it is available; TIMELESS showed no benefit when EVT was performed.
See also