TESLA
(2024)Objective
To evaluate whether endovascular thrombectomy plus medical management improves 90-day functional outcome compared with medical management alone in patients with anterior-circulation large-vessel occlusion and large infarct on noncontrast CT (ASPECTS 2-5) presenting within 24 h of onset.
Study Summary
• Trial completed full planned enrollment (302 randomized, 300 analyzed) without early stopping or enrichment.
• 90-day mRS ordinal shift (secondary): unadjusted cOR 1.40 (95% CI 0.91-2.16; P=.06).
• mRS 0-2: 14.6% vs 8.9% (diff 5.7%, −1.6 to 12.9); mRS 0-3: 29.8% vs 19.9% (diff 9.9%, 0.2-19.7; P=.03).
• 90-day mortality: 35.3% vs 33.3% (no significant difference). sICH at 24 h: 4.0% vs 1.3% (RR 2.96, 0.61-14.43).
• Sensitivity analysis in study-eligible core-lab ASPECTS: adjusted difference 0.82 (95% CrI 0.03-1.60; posterior .980) favoring thrombectomy.
Intervention
Endovascular thrombectomy (stent retriever, aspiration catheter, or both, at local interventionalist's discretion) + medical management vs medical management alone
Inclusion Criteria
Age 18-85; NIHSS ≥6; intracranial ICA or MCA M1 occlusion on CTA; ASPECTS 2-5 on noncontrast CT (site-read); presentation within 24 h of last known well; prestroke mRS 0-1. Open-label, blinded-endpoint, Bayesian-adaptive RCT at 47 US centers (Jul 2019 - Oct 2022).
Study Design
Arms: Thrombectomy + medical management vs. medical management alone
Patients per Arm: EVT n=152 vs Medical management n=148 (300 primary analysis population; 302 randomized)
Outcome
• mRS shift (secondary): cOR 1.40 (0.91-2.16; P=.06).
• mRS 0-2 at 90 d: 14.6% vs 8.9%. mRS 0-3: 29.8% vs 19.9% (P=.03).
• Major neurological improvement at day 6: 25.8% vs 12.9% (RR 2.00, 1.21-3.29; P=.004). EQ-5D at 90 d: 60 vs 50 (P=.05).
• 90-d mortality: 35.3% vs 33.3%. sICH 24 h: 4.0% vs 1.3%. Decompressive hemicraniectomy: 21.9% vs 14.8%.
• Reperfusion: mTICI 2b-3 in 73.3%, 2c-3 in 55.5%. Procedural complications in 6%.
• Post hoc by window: 0-6 h mRS 0-2 27% vs 5%; >6-24 h 10% vs 10%.
Bottom Line
In patients with a large infarct on noncontrast CT (ASPECTS 2-5) within 24 hours, thrombectomy did not significantly improve 90-day functional outcome: the primary utility-weighted mRS favored thrombectomy (adjusted difference 0.63) but the posterior probability of superiority was .96, just below the prespecified .975 threshold — a near-miss, not a futility stop. Point estimates were directionally favorable across secondary endpoints, hemorrhage rates were higher with thrombectomy, and the credible interval includes both no important effect and a clinically relevant benefit, so the authors conclude the approach likely requires additional study.
Major Points
- 302 patients randomized (300 in the primary efficacy population: 152 thrombectomy, 148 medical management) at 47 US academic and community centers, July 16, 2019 - October 17, 2022; the trial completed enrollment WITHOUT early stopping or population enrichment at either interim analysis.
- Primary endpoint: mean 90-day utility-weighted mRS 2.93 vs 2.27; adjusted difference 0.63 (95% CrI, −0.09 to 1.34); one-sided posterior probability of superiority .96, below the .975 significance threshold.
- Secondary 90-day mRS ordinal shift: unadjusted common OR 1.40 (95% CI, 0.91-2.16; P=.06).
- mRS 0-2 at 90 days: 14.6% (22/151) vs 8.9% (13/146); absolute difference 5.7% (−1.6 to 12.9). mRS 0-3 (independent ambulation): 29.8% (45/151) vs 19.9% (29/146); difference 9.9% (0.2 to 19.7; P=.03).
- Major neurological improvement at day 6/discharge: 25.8% vs 12.9% (RR 2.00, 1.21-3.29; P=.004). Median 90-day EQ-5D: 60 vs 50 (P=.05).
- 90-day mortality: 35.3% (53/150) vs 33.3% (49/147); absolute difference 2.0% (−8.8 to 12.8) — no significant difference.
- Symptomatic ICH at 24 h: 4.0% (6/151) vs 1.3% (2/149); RR 2.96 (0.61-14.43). Parenchymal hematoma type 2: 9.5% vs 3.4%; subarachnoid hemorrhage: 16.2% vs 6.2%. Decompressive hemicraniectomy: 21.9% vs 14.8%.
- Reperfusion: final mTICI 2b-3 in 73.3% (107/146), mTICI 2c-3 in 55.5%. Procedural complications in 6% (9 patients: emboli to new territory 3.3%, arterial perforation 3.3%, dissection 1.3%).
- Prespecified sensitivity analysis in patients with study-eligible core-laboratory ASPECTS: adjusted UW-mRS difference 0.82 (95% CrI, 0.03-1.60; posterior probability .980) favoring thrombectomy.
- Post hoc by time window: 0-6 h mRS 0-2 27% vs 5% (difference 22%); >6-24 h 10% vs 10%.
Study Design
- Study Type
- Pragmatic, phase 3, open-label, blinded-endpoint, Bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment
- Randomization
- Yes
- Blinding
- Blinded endpoint: mRS assessed by trained, certified local personnel unaware of treatment assignment; imaging read by core-lab radiologists unaware of assignment.
- Sample Size
- 300
- Follow-up
- 90 days (primary); 1-year outcomes published separately
- Centers
- 47
- Countries
- United States
Limitations & Criticisms
- Longest stroke-onset-to-randomization times of the large-core trials (median 10.9 h intervention, 12.6 h control) — may explain the smallest absolute treatment effects (mRS 0-2 difference 5.7%) among them; half the patients would have been ineligible for TENSION based on its 11-h limit.
- Formally negative but near-miss: the credible interval includes both no important effect and a clinically relevant benefit; the point estimate (0.63) was twice the minimum clinically important difference (0.3).
- Site-read ASPECTS drove eligibility; core-lab agreement was imperfect (some enrolled patients had core-lab ASPECTS <2 or >5), and the sensitivity analysis restricted to study-eligible core-lab ASPECTS reached posterior .980.
- Open-label treatment; site treatment-effect heterogeneity (P=.003).
Citation
JAMA. 2024;332(16):1355-1366. doi:10.1001/jama.2024.13933