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Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Title: Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial
Authors: Roaldsen, MB; Eltoft, A; Wilsgaard, T; Christensen, H; Engelter, ST; Indredavik, B; Jatužis, D; Karelis, G; Kõrv, J; Lundström, E; Petersson, J; Putaala, J; Søyland, MH; Tveiten, A; Bivard, A; Johnsen, SH; Mazya, MV; Werring, DJ; Wu, TY; De Marchis, GM; Robinson, TG; Mathiesen, EB; Parson, M; Valente, M; Chen, A; Sharobeam, A; Edwards, L; Blair, C; Christensen, L; Ægidius, K; Pihl, T; Fassel-Larsen, C; Wassvik, L; Folke, M; Rosenbaum, S; Gharehbagh, SS; Hansen, A; Preisler, N; Antsov, K; Mallene, S; Lill, M; Herodes, M; Vibo, R; Rakitin, A; Saarinen, J; Tiainen, M; Tumpula, O; Noppari, T; Raty, S; Sibolt, G; Nieminen, J; Niederhauser, J; Haritoncenko, I; Puustinen, J; Haula, TM; Sipilä, J; Viesulaite, B; Taroza, S; Rastenyte, D; Matijosaitis, V; Vilionskis, A; Masiliunas, R; Ekkert, A; Chmeliauskas, P; Lukosaitis, V; Reichenbach, A; Moss, TT; Nilsen, HY; Hammer-Berntzen, R; Nordby, LM; Weiby, TA; Nordengen, K; Ihle-Hansen, H; Stankiewiecz, M; Grotle, O; Nes, M; Thiemann, K; Særvold, IM; Fraas, M; Størdahl, S; Horn, JW; Hildrum, H; Myrstad, C; Tobro, H; Tunvold, JA; Jacobsen, O; Aamodt, N; Baisa, H; Malmberg, VN; Rohweder, G; Ellekjær, H; Ildstad, F; Egstad, E; Helleberg, BH; Berg, HH; Jørgensen, J; Tronvik, E; Shirzadi, M; Solhoff, R; Van Lessen, R
Source: The Lancet Neurology , 22 (2) pp. 117-126. (2023)
Publisher Information: ELSEVIER SCIENCE INC
Publication Year: 2023
Collection: University College London: UCL Discovery
Subject Terms: Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Neurosciences & Neurology; ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; ALTEPLASE; ONSET; THROMBOLYSIS; METAANALYSIS; TIME
Description: Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 ...
Document Type: article in journal/newspaper
File Description: text
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/10167081/
Availability: https://discovery.ucl.ac.uk/id/eprint/10167081/2/Werring_Revised_manuscript_THELANCETNEUROLOGY-D-22-008%20CLEAN.pdf; https://discovery.ucl.ac.uk/id/eprint/10167081/
Rights: open
Accession Number: edsbas.38C81389
Database: BASE