ETERNAL-LVO
(2025)Objective
To assess the efficacy and safety of tenecteplase versus standard of care in patients with large vessel occlusion stroke presenting within 24 hours of symptom onset with salvageable tissue on CT perfusion.
Study Summary
• No difference in primary outcome between tenecteplase (37%) and standard care (43%) for good functional outcome at 90 days
• Potential benefit observed in transfer patients subgroup with odds ratio of 2.61 for functional improvement
Intervention
Tenecteplase 0.25 mg/kg versus standard of care (alteplase or medical management)
Inclusion Criteria
Adults ≥18 years with anterior circulation large vessel occlusion, presenting within 24 hours of onset, with target mismatch on CT perfusion (ischemic core <70mL, penumbra >15mL, mismatch ratio >1.8)
Study Design
Arms: Tenecteplase 0.25 mg/kg vs Standard of care
Patients per Arm: 120 vs 122
Outcome
• Symptomatic ICH: 4% vs 1%
• Early study termination prevented definitive conclusions
Bottom Line
Treatment with tenecteplase did not increase the likelihood of favorable functional outcome compared to standard care, but early study termination prevents definitive conclusions from being drawn.
Major Points
- Phase 3 randomized controlled superiority trial comparing tenecteplase 0.25 mg/kg to standard care
- Study terminated early due to tenecteplase supply shortage and evolving evidence landscape
- 242 participants enrolled (median age 73 years, 43% female, 79% underwent EVT)
- No difference in primary outcome of good functional outcome at 90 days
- Potential benefit observed in transfer patient subgroup with delayed access to thrombectomy
- Higher rate of symptomatic intracerebral hemorrhage in tenecteplase group (4% vs 1%)
Study Design
- Study Type
- Prospective, randomized, open-label, blinded endpoint, phase 3, superiority trial
- Randomization
- Yes
- Blinding
- Open-label treatment, blinded outcome assessments at 90 days, blinded core imaging lab, and blinded independent clinical event adjudication committee
- Sample Size
- 242
- Follow-up
- 90 days
- Centers
- 11
- Countries
- Australia
Primary Outcome
Definition: Proportion of participants with mRS score 0-1 or return to baseline mRS at 90 days
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 43% (52/122) | 37% (44/120) | - (0.66-1.21) | 0.48 |
Limitations & Criticisms
- Early termination due to drug supply shortage and evolving evidence landscape
- Study underpowered due to early stopping (242 vs planned 740 participants)
- Loss of equipoise in <4.5 hour window during study period
- Limited to anterior circulation large vessel occlusions only
- Majority of participants (59%) presented within 4.5 hours
- Higher rate of symptomatic hemorrhage in tenecteplase group
Citation
Stroke. 2025;56:3332–3341. DOI: 10.1161/STROKEAHA.125.052511