Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke

Summary

WAKE-UP is an investigator initiated European multicenter randomized controlled clinical trial of MRI based thrombolysis in acute stroke patients with unknown time of symptom onset, e.g. due to recognition of stroke symptoms on awakening. Objective of WAKE-UP is to prove efficacy and safety of MRI-based intravenous thrombolysis with Alteplase in patients waking up with stroke symptoms or patients with otherwise unknown symptom onset.

Timeline

Start

2012-09

Primary completion

2018-10

Completion

2018-10

Outcome

Met primary endpoint

paper adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02 PMID 29766770 ↗

Publications

• Results Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, Cheripelli B, Cho TH, Fazekas F, Fiehler J, Ford I, Galinovic I, Gellissen S, Golsari A, Gregori J, Gunther M, Guibernau J, Hausler KG, Hennerici M, Kemmling A, Marstrand J, Modrau B, Neeb L, Perez de la Ossa N, Puig J, Ringleb P, Roy P, Scheel E, Schonewille W, Serena J, Sunaert S, Villringer K, Wouters A, Thijs V, Ebinger M, Endres M, Fiebach JB, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Gerloff C; WAKE-UP Investigators. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018 Aug 16;379(7):611-622. doi: 10.1056/NEJMoa1804355. Epub 2018 May 16.
• Nagele FL, Scheldeman L, Wouters A, Heinze M, Petersen M, Schlemm E, Schell M, Ebinger M, Endres M, Fiebach JB, Fiehler J, Galinovic I, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Puig J, Simonsen CZ, Thijs V, Thomalla G, Cheng B. Blood-Brain Barrier Leakage in the Penumbra Is Associated With Infarction on Follow-Up Imaging in Acute Ischemic Stroke. Stroke. 2025 Jul;56(7):1832-1842. doi: 10.1161/STROKEAHA.124.050171. Epub 2025 Apr 17.
• Galinovic I, Fiebach JB, Boutitie F, Cheng B, Cho TH, Ebinger M, Endres M, Enzinger C, Fiehler J, Ford I, Gregori J, Gunther M, Lemmens R, Muir KW, Nighoghossian N, Roy P, Simonsen CZ, Thijs VN, Wouters A, Gerloff C, Thomalla G, Pedraza S; for WAKE-UP Investigators. Effect of IV Thrombolysis With Alteplase in Patients With Vessel Occlusion in the WAKE-UP Trial. Neurology. 2025 Jan 28;104(2):e209871. doi: 10.1212/WNL.0000000000209871. Epub 2024 Dec 20.
• Frey BM, Shenas F, Boutitie F, Cheng B, Cho TH, Ebinger M, Endres M, Fiebach JB, Fiehler J, Galinovic I, Barow E, Konigsberg A, Schlemm E, Pedraza S, Lemmens R, Thijs V, Muir KW, Nighoghossian N, Simonsen CZ, Gerloff C, Thomalla G; WAKE-UP Investigators. Intravenous Thrombolysis in Patients With White Matter Hyperintensities in the WAKE-UP Trial. Stroke. 2023 Jul;54(7):1718-1725. doi: 10.1161/STROKEAHA.122.040247. Epub 2023 May 25.
• Jensen M, Sehner S, Cheng B, Schlemm E, Quandt F, Barow E, Wegscheider K, Boutitie F, Ebinger M, Endres M, Fiebach JB, Thijs V, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Simonsen CZ, Thomalla G, Gerloff C. Patient-Reported Quality of Life After Intravenous Alteplase for Stroke in the WAKE-UP Trial. Neurology. 2023 Jan 10;100(2):e154-e162. doi: 10.1212/WNL.0000000000201375. Epub 2022 Oct 27.
• Barow E, Quandt F, Cheng B, Gelderblom M, Jensen M, Konigsberg A, Boutitie F, Nighoghossian N, Ebinger M, Endres M, Fiebach JB, Thijs V, Lemmens R, Muir KW, Pedraza S, Simonsen CZ, Gerloff C, Thomalla G. Association of White Blood Cell Count With Clinical Outcome Independent of Treatment With Alteplase in Acute Ischemic Stroke. Front Neurol. 2022 Jun 13;13:877367. doi: 10.3389/fneur.2022.877367. eCollection 2022.
• Schlemm L, Braemswig TB, Boutitie F, Vynckier J, Jensen M, Galinovic I, Simonsen CZ, Cheng B, Cho TH, Fiehler J, Puig J, Thijs V, Fiebach J, Muir K, Nighoghossian N, Ebinger M, Pedraza S, Thomalla G, Gerloff C, Endres M, Lemmens R, Nolte CH; WAKE-UP Investigators. Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial. Neurology. 2022 Jan 18;98(3):e302-e314. doi: 10.1212/WNL.0000000000013055. Epub 2021 Nov 15.
• Lettow I, Jensen M, Schlemm E, Boutitie F, Quandt F, Cheng B, Ebinger M, Endres M, Fiebach JB, Thijs V, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Simonsen CZ, Gerloff C, Thomalla G; WAKE-UP Investigators. Serious Adverse Events and Their Impact on Functional Outcome in Acute Ischemic Stroke in the WAKE-UP Trial. Stroke. 2021 Dec;52(12):3768-3776. doi: 10.1161/STROKEAHA.120.033425. Epub 2021 Aug 26.
• Barow E, Boutitie F, Cheng B, Cho TH, Ebinger M, Endres M, Fiebach JB, Fiehler J, Nickel A, Puig J, Roy P, Lemmens R, Thijs V, Muir KW, Nighoghossian N, Pedraza S, Simonsen CZ, Gerloff C, Thomalla G. 24-hour blood pressure variability and treatment effect of intravenous alteplase in acute ischaemic stroke. Eur Stroke J. 2021 Jun;6(2):168-175. doi: 10.1177/23969873211014758. Epub 2021 Jun 18.
• Scheldeman L, Wouters A, Dupont P, Christensen S, Boutitie F, Cheng B, Ebinger M, Endres M, Fiebach JB, Gerloff C, Muir KW, Nighoghossian N, Pedraza S, Simonsen CZ, Ringelstein EB, Chamorro A, Grond M, Laage R, Schneider A, Thomalla G, Thijs V, Lemmens R. Reversible Edema in the Penumbra Correlates With Severity of Hypoperfusion. Stroke. 2021 Jul;52(7):2338-2346. doi: 10.1161/STROKEAHA.120.033071. Epub 2021 May 13.
• Konigsberg A, Sehner S, Arlt S, Cheng B, Simonsen CZ, Boutitie F, Serena J, Thijs V, Ebinger M, Endres M, Fiebach JB, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Gerloff C, Thomalla G; WAKE-UP investigators. Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial. Eur J Neurol. 2021 Jun;28(6):2017-2025. doi: 10.1111/ene.14797. Epub 2021 Mar 22.
• Grosch AS, Kufner A, Boutitie F, Cheng B, Ebinger M, Endres M, Fiebach JB, Fiehler J, Konigsberg A, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Siemonsen CZ, Thijs V, Wouters A, Gerloff C, Thomalla G, Galinovic I. Extent of FLAIR Hyperintense Vessels May Modify Treatment Effect of Thrombolysis: A Post hoc Analysis of the WAKE-UP Trial. Front Neurol. 2021 Feb 4;11:623881. doi: 10.3389/fneur.2020.623881. eCollection 2020.
• Barow E, Pinnschmidt H, Boutitie F, Konigsberg A, Ebinger M, Endres M, Fiebach JB, Fiehler J, Thijs V, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Simonsen CZ, Gerloff C, Thomalla G, Cheng B; WAKE-UP investigators. Symptoms and probabilistic anatomical mapping of lacunar infarcts. Neurol Res Pract. 2020 Aug 3;2:21. doi: 10.1186/s42466-020-00068-y. eCollection 2020.
• Schlemm L, Kufner A, Boutitie F, Nave AH, Gerloff C, Thomalla G, Simonsen CZ, Ford I, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Ebinger M, Endres M. Current Smoking Does Not Modify the Treatment Effect of Intravenous Thrombolysis in Acute Ischemic Stroke Patients-A Post-hoc Analysis of the WAKE-UP Trial. Front Neurol. 2019 Nov 22;10:1239. doi: 10.3389/fneur.2019.01239. eCollection 2019.
• Barow E, Boutitie F, Cheng B, Cho TH, Ebinger M, Endres M, Fiebach JB, Fiehler J, Ford I, Galinovic I, Nickel A, Puig J, Roy P, Wouters A, Thijs V, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Simonsen CZ, Gerloff C, Thomalla G; WAKE-UP investigators. Clinical Characteristics and Outcome of Patients with Lacunar Infarcts and Concurrent Embolic Ischemic Lesions. Clin Neuroradiol. 2020 Sep;30(3):511-516. doi: 10.1007/s00062-019-00800-5. Epub 2019 Jun 3.
• Thomalla G, Boutitie F, Fiebach JB, Simonsen CZ, Nighoghossian N, Pedraza S, Lemmens R, Roy P, Muir KW, Heesen C, Ebinger M, Ford I, Cheng B, Cho TH, Puig J, Thijs V, Endres M, Fiehler J, Gerloff C. Effect of informed consent on patient characteristics in a stroke thrombolysis trial. Neurology. 2017 Sep 26;89(13):1400-1407. doi: 10.1212/WNL.0000000000004414. Epub 2017 Aug 25.
• Thomalla G, Boutitie F, Fiebach JB, Simonsen CZ, Pedraza S, Lemmens R, Nighoghossian N, Roy P, Muir KW, Ebinger M, Ford I, Cheng B, Galinovic I, Cho TH, Puig J, Thijs V, Endres M, Fiehler J, Gerloff C. Clinical characteristics of unknown symptom onset stroke patients with and without diffusion-weighted imaging and fluid-attenuated inversion recovery mismatch. Int J Stroke. 2018 Jan;13(1):66-73. doi: 10.1177/1747493017706245. Epub 2017 Apr 20.
• Thomalla G, Boutitie F, Fiebach JB, Simonsen CZ, Nighoghossian N, Pedraza S, Lemmens R, Roy P, Muir KW, Ebinger M, Ford I, Cheng B, Galinovic I, Cho TH, Puig J, Thijs V, Endres M, Fiehler J, Gerloff C; WAKE-UP Investigators. Stroke With Unknown Time of Symptom Onset: Baseline Clinical and Magnetic Resonance Imaging Data of the First Thousand Patients in WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke: A Randomized, Doubleblind, Placebo-Controlled Trial). Stroke. 2017 Mar;48(3):770-773. doi: 10.1161/STROKEAHA.116.015233. Epub 2017 Feb 7.

Drugs

Indications