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TESLA

Thrombectomy for Stroke With Large Infarct on Noncontrast CT: The TESLA Randomized Clinical Trial

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Year of Publication: 2024

Authors: The Writing Committee for the TESLA Investigators (corresponding: Osama O. Zaidat)

Journal: JAMA

Citation: JAMA. 2024;332(16):1355-1366. doi:10.1001/jama.2024.13933

Link: https://jamanetwork.com/journals/jama/fullarticle/2823962

Clinical Question

In patients with anterior-circulation LVO and large infarct (ASPECTS 2-5) on noncontrast CT presenting within 24 h, does endovascular thrombectomy plus medical management improve 90-day functional outcome compared with medical management alone?

Study Overview

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

  • Primary (90-day mean utility-weighted mRS): 2.93 vs 2.27; adjusted difference 0.63 (95% CrI −0.09 to 1.34); posterior probability of superiority .96 — below the prespecified .975 threshold, so NOT statistically significant (near-miss).
  • 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

Patients per Arm

EVT n=152 vs Medical management n=148 (300 primary analysis population; 302 randomized)

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%.

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: 1

Blinding: Blinded endpoint: mRS assessed by trained, certified local personnel unaware of treatment assignment; imaging read by core-lab radiologists unaware of assignment.

Enrollment Period: July 16, 2019 - October 17, 2022; final follow-up January 25, 2023

Follow-up Duration: 90 days (primary); 1-year outcomes published separately

Centers: 47

Countries: United States

Sample Size: 300

Analysis: Bayesian model adjusting for baseline ASPECTS; superiority required one-sided posterior probability ≥.975. Interim analyses at 150 and 225 patients — the trial continued without enrichment or stopping at each. Randomization stratified by age (≤70/>70), baseline ASPECTS (2-3 vs 4-5), NIHSS (≤16/>16), and onset-to-imaging window. Powered at 90% for an assumed UW-mRS effect of 1.25.

Inclusion Criteria

  • Age 18 to 85 years.
  • NIHSS score ≥6.
  • Intracranial ICA or MCA M1-segment occlusion on CT angiography.
  • Large infarct on noncontrast CT: ASPECTS 2 to 5, determined by trained/certified site investigators.
  • Presentation within 24 hours of symptom onset or last known well.
  • Prestroke mRS 0-1 (excellent baseline functional status).
  • IV alteplase, if indicated, administered within 3 hours of onset per FDA guidance.

Exclusion Criteria

  • Intracranial hemorrhage.
  • Mass effect with ventricular effacement, midline shift, or herniation.
  • Tandem cervical internal carotid artery occlusion.

Outcomes

Primary

Mean 90-day utility-weighted mRS: 2.93 (SD 3.39) vs 2.27 (SD 2.98); adjusted difference 0.63 (95% CrI −0.09 to 1.34); posterior probability of superiority .96 (threshold .975) — not significant.

Secondary

  • 90-day mRS ordinal shift: unadjusted cOR 1.40 (95% CI 0.91-2.16; P=.06).
  • mRS 0-2: 14.6% vs 8.9% (difference 5.7%, −1.6 to 12.9; P=.09).
  • mRS 0-3: 29.8% vs 19.9% (difference 9.9%, 0.2-19.7; P=.03).
  • Major neurological improvement day 6/discharge: 25.8% vs 12.9% (RR 2.00, 1.21-3.29; P=.004).
  • Median 90-day EQ-5D: 60 (IQR 30-75) vs 50 (IQR 23.5-65); P=.05.
  • 24-h median NCCT/DWI infarct volume: 166 vs 171 mL.
  • Final mTICI 2b-3: 73.3%; mTICI 2c-3: 55.5%.

Safety

  • 90-day mortality (primary adverse endpoint): 35.3% (53/150) vs 33.3% (49/147); difference 2.0% (−8.8 to 12.8); RR 1.06 (0.77-1.45).
  • Symptomatic ICH at 24 h: 4.0% (6/151) vs 1.3% (2/149); RR 2.96 (0.61-14.43).
  • Parenchymal hematoma type 1: 9.5% vs 2.7%; type 2: 9.5% vs 3.4%; subarachnoid hemorrhage: 16.2% vs 6.2%.
  • Decompressive hemicraniectomy: 21.9% vs 14.8% (RR 1.48, 0.91-2.42).
  • Procedural complications: 6% (emboli to new territory 3.3%; arterial perforation 3.3%; arterial dissection 1.3%).

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).

Subgroup Analysis

No compelling evidence of treatment-effect modification across prespecified subgroups (age, sex, ASPECTS, NIHSS, occlusion location, IV alteplase, time to randomization, COVID-19 status, first-line technique, CT-perfusion mismatch — CTP available in fewer than half). Site poolability analysis indicated heterogeneity of site treatment effects (interaction P=.003). Prespecified sensitivity analysis in study-eligible core-lab ASPECTS favored thrombectomy (adjusted difference 0.82; 95% CrI 0.03-1.60; posterior .980). Post hoc by window: benefit concentrated 0-6 h (mRS 0-2 27% vs 5%); attenuated >6-24 h (10% vs 10%).

Funding

Funded through unrestricted grants from Medtronic, Cerenovus, Penumbra, Stryker, and Genentech. The funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit for publication.

Based on: TESLA (JAMA, 2024)

Authors: The Writing Committee for the TESLA Investigators (corresponding: Osama O. Zaidat)

Citation: JAMA. 2024;332(16):1355-1366. doi:10.1001/jama.2024.13933

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