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

Abstract

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset.

Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset.

Design, setting, and participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023.

Intervention: The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone.

Main outcomes and measures: The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of .975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage.

Results: The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], -0.09 to 1.34; posterior probability for superiority of thrombectomy, .96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages.

Conclusions and relevance: Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study.

Trial registration: ClinicalTrials.gov Identifier: NCT03805308.

Figure 1.. Randomization and Flow of Patients Through the TESLA Study

^aRandomization was stratified for age (≤70 or >70 years), baseline ASPECTS (2-3 vs 4-5), baseline NIHSS score (≤16 or >16), and time from onset to imaging (0-6 hours vs >6-24 hours). Sites were not required to maintain screening logs. ^bThe 30-day modified Rankin Scale score was used to impute 90-day score in the primary efficacy analysis.

Figure 2.. Modified Rankin Scale Scores at 90 Days in the Primary Efficacy Analysis Population

The 90-day ordinal modified Rankin Scale (mRS) score was a secondary efficacy end point. The distribution of the scores is shown by treatment group. Scores range from 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability, 2 slight disability (patient is able to look after own affairs without assistance but is unable to carry out all previous activities), 3 moderate disability (patient requires some help but is able to walk unassisted), 4 moderately severe disability (patient is unable to attend to bodily needs without assistance and unable to walk unassisted), 5 severe disability (patient requires constant nursing care and attention), and 6 death. The unadjusted common odds ratio for improvement on the mRS score at 90 days with intervention was 1.40 (95% CI, 0.91 to 2.16). In the thrombectomy group, 1 participant was lost to follow-up at 90 days, yielding 151 patients with available 90-day mRS scores. For the primary analysis, this participant’s 30-day mRS score was imputed for the 90-day analysis. In the medical therapy alone group, 1 participant was lost to follow-up at 90 days, and 1 participant withdrew consent at the day-6 visit, yielding 146 patients with available 90-day mRS scores.