Journal article

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Goetz Thomalla, Florent Boutitie, Henry Ma, Masatoshi Koga, Peter Ringleb, Lee H Schwamm, Ona Wu, Martin Bendszus, Christopher F Bladin, Bruce CV Campbell, Bastian Cheng, Leonid Churilov, Martin Ebinger, Matthias Endres, Jochen B Fiebach, Mayumi Fukuda-Doi, Manabu Inoue, Timothy J Kleinig, Lawrence L Latour, Robin Lemmens Show all

The Lancet | ELSEVIER SCIENCE INC | Published : 2020

Abstract

BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary out..

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Grants

Awarded by EU Seventh Framework programme


Awarded by Japan Agency for Medical Research and Development (AMED)


Awarded by NIH National Institute of Neurological Disorders and Stroke (NINDS) Specialized Program of Transitional Research in Acute Stroke (SPOTRIAS)


Awarded by NINDS Division of Intramural Research


Funding Acknowledgements

WAKE-UP was supported by a grant (number 278276) from the EU Seventh Framework programme. EXTEND was funded by the National Health and Medical Research Council, an Australian Government organisation and Commonwealth Scientific and Industrial Research Organisation. Boehringer Ingelheim provided the study investigational products free of charge. THAWS was supported by the Japan Agency for Medical Research and Development (AMED; 19ek0210091h0003 and 19lk0201094h0001), and the Ministry of Health, Labour, and Welfare, and the Mihara Cerebrovascular Disorder Research Promotion Fund. ECASS-4 was an investigator-initiated trial supported by an unrestricted grant from Boehringer Ingelheim (Germany). MR WITNESS was supported by the NIH National Institute of Neurological Disorders and Stroke (NINDS) Specialized Program of Transitional Research in Acute Stroke (SPOTRIAS; P50-NS051343) and NINDS Division of Intramural Research, was done in part at the Athinoula A Martinos Center for Biomedical Imaging at Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies (P41EB015896), a P41 Biotechnology Resource Grant supported by the NIH National Institute of Biomedical Imaging and Bioengineering. Genentech provided alteplase free of charge to the study for distribution to all sites except to the NINDS intramural branch and starting in year 2 provided supplemental site payments to permit expansion to 14 sites.