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Observational Study
. 2026 Jan 1;83(1):60-67.
doi: 10.1001/jamaneurol.2025.4712.

Intravenous Thrombolysis Use in the Late Time Window Before Interhospital Transfer for Thrombectomy

Pierre Seners  1   2   3 , Nour Nehme  4 , Adrien Ter Schiphorst  2   5 , Frédérique Charbonneau  6 , Nicolas Chausson  2   7 , Marie Belley  8   9 , Anne Wacongne  10 , Olfa Kaaouana  11 , Carole Henry  12 , Andrei Girbovan  13 , Omar Naciri Bennani  14 , Benjamin Maïer  3   15   16 , Mathilde Dupin  17 , Gaspard Gerschenfeld  2   3   18 , François Lun  19 , Guillaume Marc  20 , Jérémie Dassa  21 , Tristan Benoit  22 , Denis Sablot  23 , Julia Loeillot  24 , Julien Rigal  25 , Didier Smadja  2   7 , Luca Scarcia  26 , Jildaz Caroff  27 , Fernando Pico  3   8   9 , Hilde Henon  28 , Stéphane Skerlak  29 , Florian Basille  30 , Wagih Ben Hassen  31 , Gaultier Marnat  32 , Julien Allard  33 , Loïc Legris  34 , Romain Bourcier  35 , Géraud Forestier  36 , Cyril Chivot  37 , Gregory W Albers  38 , Maarten G Lansberg  38 , Guillaume Turc  2   3   39 , Jérémie Papassin  3   40 ; OPEN-WINDOW collaborators
Collaborators, Affiliations
Observational Study

Intravenous Thrombolysis Use in the Late Time Window Before Interhospital Transfer for Thrombectomy

Pierre Seners et al. JAMA Neurol. .

Abstract

Importance: In patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), the benefit of intravenous thrombolysis (IVT) administered beyond 4.5 hours from the last time known well before endovascular therapy (EVT) is uncertain. Recently, the TIMELESS trial failed to demonstrate a benefit of IVT in this setting, but this trial focused on patients directly admitted to comprehensive stroke centers (CSCs) with fast access to EVT.

Objective: To assess the efficacy and safety of IVT initiated beyond 4.5 hours in patients with AIS-LVO initially admitted to primary stroke centers (PSCs) and subsequently transferred to a CSC for EVT, allowing substantial time for the IVT to take effect.

Design, setting, and participants: This multicenter retrospective cohort study was conducted between January 2020 and December 2024, with 3-month follow-up, at 20 French PSCs. All consecutive patients with AIS-LVO admitted beyond 4.5 hours from the last time they were known well in the PSC and subsequently transferred to a CSC for EVT, with or without IVT administered prior to transfer, were eligible for inclusion. Data analysis was performed between May 2025 and July 2025.

Main outcomes and measures: The primary outcome was the 3-month modified Rankin Scale score, analyzed in the ordinal approach. Propensity score with overlap weighting (PSOW) balanced covariates between patients treated with IVT vs those without.

Results: A total of 584 patients were included, among whom 309 patients (52.9%) were female. Median (IQR) age was 71 (61-81) years, median (IQR) baseline National Institutes of Health Stroke scale score was 15 (10-19), median (IQR) time from last known well to PSC imaging was 10.5 (6.9-14.0) hours, and 232 patients (39.7%) received IVT before transfer. Advanced brain imaging (magnetic resonance imaging or computed tomography [CT] with CT-perfusion) was performed at the PSC in 544 patients (93.2%). IVT use before transfer was independently associated with a shift toward better 3-month outcomes (PSOW-common odds ratio [OR], 1.97; 95% CI, 1.33-2.92; P = .001) and higher odds of recanalization during transfer (PSOW-OR, 8.69; 95% CI, 3.16-23.87; P < .001) compared with those without. The rate of any intracerebral hemorrhage and symptomatic intracerebral hemorrhage were similar between groups.

Conclusions and relevance: In this multicenter cohort study, IVT initiated beyond 4.5 hours prior to interhospital transfer for EVT was associated with higher rates of recanalization during transfer and improved 3-month functional outcomes, without safety concerns. These findings offer encouraging support for clinical trials evaluating IVT in the late time window before interhospital transfer.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Seners reported speaker fees from Boerhinger Ingelheim outside the submitted work. Dr Gerschenfeld reported personal fees from Truffle Capital and grants from Boehringer Ingelheim and Programme Hospitalier de Recherche Clinique outside the submitted work. Dr Marnat reported consulting fees from Balt SAS, Microvention/Terumo Neuro, Sim and Cure, and Stryker Neurovascular and lecture fees from Bracco, Medtronic, Penumbra, and Wallaby Phenox outside the submitted work. Dr Albers reported consulting fees from and holding equity in iSchemaView outside the submitted work. Dr Lansberg reported grants from the US National Institutes of Health/National Institute of Neurological Disorders and Stroke during the conduct of the study and serving as a member of a steering committee of a clinical trial from Roche/Genetech outside the submitted work. Dr Turc reported lecture fees from Guerbet France; serving as a member of a scientific advisory board for IA Stroke; and consulting fees from Neurologica outside the submitted work. No other disclosures were reported.

References

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