ETIS-TETRIS
(2026)Objective
To assess whether IV tenecteplase plus thrombectomy (TNK + EVT) is associated with better 3-month functional outcomes compared with EVT alone in anterior circulation LVO stroke patients treated within 4.5 hours, and to determine whether any benefit is time-dependent.
Study Summary
• The functional benefit of tenecteplase before EVT was not time-dependent and did not differ significantly by admission center type (primary vs. comprehensive stroke center).
• These real-world registry findings support routine use of tenecteplase bridging before thrombectomy in the early time window.
Intervention
IV tenecteplase (0.25 mg/kg, max 25 mg) followed by intended endovascular thrombectomy (TNK + EVT) vs. endovascular thrombectomy alone (EVT)
Inclusion Criteria
Adults with anterior circulation LVO stroke (intracranial ICA, M1 or M2 MCA occlusion +/- tandem cervical ICA occlusion); known symptom onset within 4.5 hours; no contraindication to thrombolysis except infarct size; not on anticoagulants pre-stroke
Study Design
Arms: TNK + EVT (TETRIS registry) vs. EVT alone (ETIS registry)
Patients per Arm: TNK + EVT: 798; EVT alone: 1,092
Outcome
• 3-month functional independence (mRS <=2): 51.0% vs. 40.4%, OR 1.50 (95% CI 1.23-1.84), p < 0.001
• sICH: 4.5% vs. 4.5%, OR 1.13 (95% CI 0.69-1.86), p = 0.61; parenchymal hematoma: 12.1% vs. 10.3%, OR 1.29 (95% CI 0.94-1.79), p = 0.12 (no significant difference)
Bottom Line
In this large real-world pooled registry analysis, TNK + EVT was associated with significantly better 3-month functional outcomes compared with EVT alone, without an increase in hemorrhagic complications. The benefit was not time-dependent and did not differ by admission center type (primary vs. comprehensive stroke center), supporting routine tenecteplase use before thrombectomy in the early time window.
Major Points
- Retrospective pooled analysis of two nationwide prospective French registries: TETRIS (TNK + EVT) and ETIS (EVT alone), covering January 2015 to March 2024
- 1,890 patients analyzed after propensity score overlap weighting (PSOW) to balance baseline confounders
- TNK + EVT was associated with better 3-month ordinal mRS shift (OR 1.53, 95% CI 1.29-1.82, p < 0.001) and functional independence (mRS <=2: 51.0% vs. 40.4%, OR 1.50, p < 0.001)
- No significant difference in sICH (4.5% vs. 4.5%, p = 0.61) or parenchymal hematoma (12.1% vs. 10.3%, p = 0.12)
- No significant treatment effect modification across onset-to-thrombolysis time (p-interaction = 0.11), contrasting with alteplase data from the IRIS meta-analysis
- No significant interaction between admission center type (PSC vs. CSC) and treatment effect (p-interaction = 0.12), though numerically higher OR in PSC-admitted patients (1.75 vs. 1.29)
- Lower EVT rate in TNK + EVT group (85.5% vs. 96.2%) likely reflecting pre-EVT recanalization attributable to tenecteplase
- Class II evidence per AAN classification
Study Design
- Study Type
- Retrospective pooled analysis of two prospective multicenter nationwide real-world registries
- Randomization
- No
- Blinding
- No blinding; outcomes assessed unblinded in real-world conditions
- Sample Size
- 1890
- Follow-up
- 3 months
- Countries
- France
Primary Outcome
Definition: 3-month functional outcome assessed by ordinal modified Rankin Scale (mRS) shift analysis - improvement of at least 1 point on the mRS
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median mRS 3 (IQR 1-5) | Median mRS 2 (IQR 1-4) | 1.53 (1.29-1.82) | <0.001 |
Limitations & Criticisms
- Retrospective pooled registry design with unmeasured confounding that PSOW cannot fully address
- Two treatment groups drawn from different patient populations and largely different stroke centers, increasing residual confounding risk despite weighting
- Outcomes assessed unblinded in real-world conditions, introducing potential mRS misclassification bias
- Pre-EVT recanalization data unavailable for most patients, limiting mechanistic interpretation
- Patients enrolled over 9 years; temporal changes in clinical practice may introduce time-period bias
- Expected onset-to-thrombolysis time in the EVT-alone group was derived (not directly observed), introducing estimation error
- mRS at hospital discharge not routinely collected, precluding use for imputing missing 3-month mRS values
- Brain imaging assessed locally (not centrally), potentially introducing site variability
- TNK + EVT group had longer onset-to-reperfusion times, which may have partially offset the benefit of tenecteplase
- Declared reasons for IVT omission in ETIS may be incomplete, and unrecorded contraindications could introduce selection bias
Citation
Neurology 2026;106:e214702