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Randomized Controlled Trial
. 2025 Jun 1;82(6):589-596.
doi: 10.1001/jamaneurol.2025.0716.

CT Perfusion Imaging After Selection for Late-Window Endovascular Stroke Treatment: Secondary Analysis of the MR CLEAN-LATE Randomized Trial

Susanne G H Olthuis  1   2 , Florentina M E Pinckaers  2   3 , M M Quirien Robbe  2   3 , Inger R de Ridder  1   2 , Jan W Hoving  4 , Esmee Venema  5   6 , Jasper D Daems  5   7 , F A V Anne Pirson  1   2 , Julie Staals  1   2 , Bart J Emmer  4 , Hester F Lingsma  5 , Stefan D Roosendaal  4 , Anouk van der Hoorn  8 , Miou S Koopman  4 , Alida A Postma  3   9 , Diederik W J Dippel  7 , Charles B Majoie  4 , Robert J van Oostenbrugge  1   2 , Wim H van Zwam  2   3 ; MR CLEAN-LATE (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands for Late Arrivals) Investigators
Collaborators, Affiliations
Randomized Controlled Trial

CT Perfusion Imaging After Selection for Late-Window Endovascular Stroke Treatment: Secondary Analysis of the MR CLEAN-LATE Randomized Trial

Susanne G H Olthuis et al. JAMA Neurol. .

Abstract

Importance: MR CLEAN-LATE (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands for Late Arrivals) showed efficacy of endovascular treatment (EVT) in the late window (6-24 hours after stroke symptom onset or time last seen well) among patients with ischemic stroke selected based on collateral flow. Therefore, the future role of computed tomography perfusion (CTP) imaging in patient selection for late-window EVT may change.

Objective: To investigate the interaction among CTP parameters (core volumes, penumbra volumes, and mismatch ratio) and the association of EVT with functional outcomes among patients in the late window after ischemic stroke selected based on collateral flow.

Design, setting, and participants: This is a post hoc secondary analysis of MR CLEAN-LATE, a multicenter randomized clinical trial, with open-label treatment and blinded end point, conducted from February 2, 2018, to January 27, 2022, in 18 Dutch stroke intervention centers. Participants included 502 patients with anterior circulation large vessel occlusion and present collateral flow on results of computed tomographic angiography in the late window after stroke, who gave deferred consent and were included in MR CLEAN-LATE. All patients had completed follow-up at 90 days. This secondary analysis included 313 patients (62%) with available CTP results. Statistical analysis was performed in September 2023.

Intervention: Patients were randomized to receive EVT (EVT group) and best medical management vs best medical management alone (no EVT group).

Main outcomes and measures: The primary outcome was functional outcome at 90 days measured by the modified Rankin Scale score. The treatment effect was analyzed in subgroups of core volumes, penumbra volume, and mismatch ratios using ordinal regression analysis. An interaction analysis was performed to assess whether CTP parameters modified the EVT effect on the modified Rankin Scale score at 90 days. All analyses were adjusted for relevant prognostic factors.

Results: Among the 313 patients (158 women [50%]) in the study, the median age was 73 years (IQR, 63-80 years), and the EVT group had fewer male participants than the no EVT group (73 of 168 [43%] vs 82 of 145 [57%]). Penumbra volumes significantly modified the association of EVT with outcomes (P < .001 for interaction), with the largest effect size among patients with penumbras of 120 mL or more (adjusted common odds ratio [ACOR], 6.89 [95% CI, 2.96-16.04]) and the smallest effect size among patients with penumbras of 72 mL or less (ACOR, 0.49 [95% CI, 0.22-1.08]). Core volume and mismatch ratio did not modify the EVT effect.

Conclusions and relevance: Based on results from this secondary analysis of the MR CLEAN-LATE randomized clinical trial, there was a direct interaction between penumbra volume and treatment effect, and a trend toward potential harm of EVT was seen among patients with the smallest penumbras, which warrants further research. However, core volume and mismatch ratio did not seem to have additional value in patient selection.

Trial registration: isrctn.org Identifier: ISRCTN19922220.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Staals reported receiving personal fees from Medtronic outside the submitted work. Dr Emmer reported receiving grants from Leading The Change (Dutch Science Foundation) paid to institution during the conduct of the study. Dr Postma reported receiving grants from Siemens Healthineers paid to institution outside the submitted work. Dr Dippel reported receiving grants from Medtronic, Stryker, Thrombolytic Science International, Cerenovus, and Penumbra paid to institution outside the submitted work. Dr Majoie reported receiving grants from CVON/Dutch Heart Foundation, European Commission, Stryker, Boehringer Ingelheim, and Healthcare Evaluation Netherlands paid to institution outside the submitted work; and being a shareholder of Nicolab (minority interest). Dr van Zwam reported receiving grants from Dutch Heart Foundation, ZonMW, and the Dutch Brain Council paid to institution during the conduct of the study; and other from Philips paid to institution, other from Stryker paid to institution, other from Cerenovus paid to institution, and other from Nicolab paid to institution outside the submitted work. No other disclosures were reported.

Comment in

References

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