Tenecteplase in wake-up ischemic stroke trial: Protocol for a randomized-controlled trial.

Melinda B Roaldsen,Stefan T Engelter,Arnstein Tveiten,David J Werring,Eivind Berge,Jukka Putaala,Ellisiv B Mathiesen,Janika Kõrv,Hanne Christensen,Thompson Robinson,Gian Marco De Marchis,Tom Wilsgaard,Dalius Jatužis,Mary-Helen Søyland,Agnethe Eltoft,Mirza Jusufovic,Jesper Petersson,Haakon Lindekleiv,Bent Indredavik

doi:10.1177/1747493020984073

Abstract

BackgroundPatients with wake-up ischemic stroke who have evidence of salvageable tissue on advanced imaging can benefit from intravenous thrombolysis. It is not known whether patients who do not fulfil such imaging criteria might benefit from treatment, but studies indicate that treatment based on non-contrast CT criteria may be safe. Tenecteplase has shown promising results in patients with acute ischemic stroke. The aim of the Tenecteplase in Wake-up Ischemic Stroke Trial (TWIST) is to compare the effect of thrombolytic treatment with tenecteplase and standard care versus standard care alone in patients with wake-up ischemic stroke selected by non-contrast CT.Methods/designTWIST is an international, investigator-initiated, multi-centre, prospective, randomized-controlled, open-label, blinded end-point trial of tenecteplase (n = 300) versus standard care (n = 300) in patients who wake up with an acute ischemic stroke and can be treated within 4.5 h upon awakening. Seventy-seven centres in 10 countries (Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom) participate. The primary outcome is the modified Rankin Scale on the ordinal scale (0–6) at three months.DiscussionTWIST aims to determine the effect and safety of thrombolytic treatment with tenecteplase in patients with wake-up ischemic stroke selected by non-contrast CT.Trial registrationClinicalTrials.gov NCT03181360. EudraCT Number 2014-000096-80.

Highlights

Introduction and rationaleThrombolytic treatment with intravenous recombinant tissue plasminogen activator given within 4.5 h of onset improves clinical outcome after ischemic stroke.[1]
About one in five ischemic strokes occur during sleep,[2] and these strokes have traditionally been considered ineligible for thrombolytic treatment because the time of onset is unknown
Thrombolytic treatment has been shown to be effective in patients who fulfil advanced imaging criteria, it is possible that thrombolysis will benefit patients without such radiologic findings as well

Summary

Introduction

Introduction and rationaleThrombolytic treatment with intravenous recombinant tissue plasminogen activator (rt-PA) given within 4.5 h of onset improves clinical outcome after ischemic stroke.[1]. Previous studies have shown that DWI/FLAIR mismatch can be absent in as many as 40% of patients with known stroke duration of less than 3 h,5 indicating that selection of patients based on advanced imaging criteria could exclude WUS patients who might benefit from thrombolysis. Patients with wake-up ischemic stroke who have evidence of salvageable tissue on advanced imaging can benefit from intravenous thrombolysis It is not known whether patients who do not fulfil such imaging criteria might benefit from treatment, but studies indicate that treatment based on non-contrast CT criteria may be safe. The aim of the Tenecteplase in Wake-up Ischemic Stroke Trial (TWIST) is to compare the effect of thrombolytic treatment with tenecteplase and standard care versus standard care alone in patients with wake-up ischemic stroke selected by non-contrast CT

Objectives

Methods

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Conclusion