Hernández-Pérez, MaríaValls-Carbó, AdriánHernández-Jiménez, MacarenaMolina, Carlos A.Vivancos, JoséCastellanos, María del MarGarcía-Madrona, SebastiánTembl, José IgnacioMoniche, FranciscoTerceño, MikelCardona, PereArenillas, JuanCalleja, PatriciaHenon, HildeCalviere, LionelMazighi, MikaelOlivot, Jean MarcLiebeskind, David S.Ribó, Marc2025-09-092025-09-092025-07-18Hernández-Pérez M, Valls-Carbó A, Hernández-Jiménez M, Molina C, Vivancos Mora J, Castellanos M, García-Madrona S, Tembl JI, Moniche F, Terceño M, Cardona P, Arenillas JF, Calleja P, Henon H, Calviere L, Mazighi M, Olivot JM, Liebeskind DS, Ribo M. Changes in infarct volume and cerebral edema after mechanical thrombectomy in patients with stroke randomized to ApTOLL or placebo: a secondary analysis of APRIL trial. Stroke. 2025 Sep;56(9):2422-2430.0039-2499https://hdl.handle.net/2183/45732Clinical trial[Abstract] Background: APRIL (A Double-Blind, Placebo-Controlled, Randomized, Phase Ib/IIa Clinical Study of ApTOLL for the Treatment of Acute Ischemic Stroke), a randomized placebo-controlled phase Ib/IIa trial, showed safety and reduced mortality and disability at 90 days of ApTOLL 0.2 mg/kg in combination with endovascular treatment in patients with acute large vessel occlusion within a 6-hour window. We studied the effect of ApTOLL against placebo on final infarct volume, infarct growth, and cerebral edema. Methods: Post hoc analysis of a trial was conducted between 2020 and 2022 in Spain and France. Patients allocated to ApTOLL doses of 0.05 and 0.2 mg/kg and placebo were selected. The early infarct growth rate was defined as admission relative cerebral blood flow <30% volume/time elapsed from last-known well to imaging, considering fast progressors when >10 mL/h. An imaging core laboratory evaluated final infarct volume and cerebral edema on fluid-attenuated inversion recovery or noncontrast computed tomography at 72 hours if fluid-attenuated inversion recovery was not available. Cerebral edema was evaluated according to the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) edema scale (cerebral edema degree [CED]; less severe: CED1; more severe: CED2; and with midline shift: CED3). Infarct growth was calculated as the final infarct volume: relative cerebral blood flow <30% volume at admission. Associations were studied through linear or ordinal models adjusted by prespecified variables. Admission relative cerebral blood flow <30% volume, fast recruitment, and final expanded Thrombolysis in Cerebral Infarction, among others, were examined for interaction with ApTOLL on final infarct volume and CED. Results: A total of 136 of 139 patients had sufficient radiological data. Median admission relative cerebral blood flow <30% was 18 mL, and median final infarct volume was 36.53 mL. Edema grade was CED1 in 45%, CED2 in 34%, and CED3 in 21% patients. Compared with placebo, ApTOLL 0.2 mg/kg was independently associated with a lower final infarct volume (relative reduction, -45.2% [95% CI, -65% to -15%]), a lower infarct growth (61.51% [95% CI, -79% to -29%]), and a lower edema grade (common odds ratio, 0.38 [95% CI, 0.15-0.96]). No associations were found for ApTOLL 0.05 mg/kg. The study of interactions showed a greater benefit of ApTOLL 0.2 mg/kg among patients with larger core volume at admission, fast progressors, and patients achieving incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction <2b). Conclusions: ApTOLL 0.2 mg/kg in combination with mechanical thrombectomy significantly reduced final infarct volume, infarct growth, and cerebral edema at 72 hours. ApTOLL seemed to be more effective under conditions prone to infarct growth.engBlood-brain barrierCerebral edemaIschemic strokePrognosisThrombectomyjournal articleopen access10.1161/strokeaha.124.048917