Top

Published in:

Open Access 01-12-2022 | Stroke | Update

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

Authors: Agnethe Eltoft, Tom Wilsgaard, Melinda B. Roaldsen, Mary-Helen Søyland, Erik Lundström, Jesper Petersson, Bent Indredavik, Jukka Putaala, Hanne Christensen, Janika Kõrv, Dalius Jatužis, Stefan T. Engelter, Gian Marco De Marchis, David J. Werring, Thompson Robinson, Arnstein Tveiten, Ellisiv B. Mathiesen

Published in: Trials | Issue 1/2022

Abstract

Background

Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings.

Objective

To publish the detailed statistical analysis plan for TWIST prior to unblinding.

Methods

The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting.

Discussion

Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.

Trial registration

ClinicalTrials.govNCT03181360. EudraCT Number 2014-000096-80. WHO ICRTP registry number ISRCTN10601890.

Available only for authorised users

Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J. 2018;379:611–22. 2018/05/17. https://doi.org/10.1056/NEJMoa1804355.CrossRef

Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019;380:1795–803. https://doi.org/10.1056/NEJMoa1813046.CrossRefPubMed

Thomalla G, Boutitie F, Ma H, et al. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data. Lancet. 2020;396:1574–84. 2020/11/12. https://doi.org/10.1016/s0140-6736(20)32163-2.CrossRefPubMedPubMedCentral

Roaldsen MB, Lindekleiv H, Eltoft A, et al. Tenecteplase in wake-up ischemic stroke trial: Protocol for a randomized-controlled trial. Int J Stroke. 2021;1747493020984073. 2021/01/16. https://doi.org/10.1177/1747493020984073.

Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332. 2010/03/25. https://doi.org/10.1136/bmj.c332.CrossRefPubMedPubMedCentral

Haybittle JL. Repeated assessment of results in clinical trials of cancer treatment. Br J Radiol. 1971;44:793–7. 1971/10/01. https://doi.org/10.1259/0007-1285-44-526-793.CrossRefPubMed

Saver JL. Novel end point analytic techniques and interpreting shifts across the entire range of outcome scales in acute stroke trials. Stroke. 2007;38:3055–62. 2007/10/06. https://doi.org/10.1161/strokeaha.107.488536.CrossRefPubMed

Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet. 2007;369:275–82. 2007/01/30. https://doi.org/10.1016/s0140-6736(07)60149-4.CrossRefPubMed

Group ISTc. Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial. Lancet Neurol. 2013;12:768–76. 2013/06/25. https://doi.org/10.1016/S1474-4422(13)70130-3.CrossRef

10.

Rv K, Broderick JP, BCV C, et al. The Heidelberg Bleeding Classification. Stroke. 2015;46:2981–6. https://doi.org/10.1161/STROKEAHA.115.010049.CrossRef

11.

Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet. 2012;379:2364–72. 2012/05/29. https://doi.org/10.1016/s0140-6736(12)60738-7.CrossRefPubMedPubMedCentral

12.

Zhu RL, Xu J, Xie CJ, et al. Efficacy and safety of thrombolytic therapy for stroke with unknown time of onset: a meta-analysis of observational studies. J Stroke Cerebrovasc Dis. 2020;29:104742. 2020/03/05. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104742.CrossRefPubMed

13.

Senn S. Statistical Issues in Drug Development. 2nd ed. Chichester: Wiley; 2008. p. 173.

14.

Churilov L, Arnup S, Johns H, et al. An improved method for simple, assumption-free ordinal analysis of the modified Rankin Scale using generalized odds ratios. Int J Stroke. 2014;9:999–1005. 2014/09/10. https://doi.org/10.1111/ijs.12364.CrossRefPubMed

Title: Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)
Authors: Agnethe Eltoft
Tom Wilsgaard
Melinda B. Roaldsen
Mary-Helen Søyland
Erik Lundström
Jesper Petersson
Bent Indredavik
Jukka Putaala
Hanne Christensen
Janika Kõrv
Dalius Jatužis
Stefan T. Engelter
Gian Marco De Marchis
David J. Werring
Thompson Robinson
Arnstein Tveiten
Ellisiv B. Mathiesen
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Stroke
Tenecteplase
Published in: Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-022-06301-0

2024 ASCO Annual Meeting

Springer Medicine

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

Abstract

Background

Objective

Methods

Discussion

Trial registration

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Objective

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2022

Efficacy and safety of Lenzumestrocel (Neuronata-R® inj.) in patients with amyotrophic lateral sclerosis (ALSUMMIT study): study protocol for a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial

Impact of propofol versus sevoflurane on the incidence of postoperative delirium in elderly patients after spine surgery: study protocol of a randomized controlled trial

A double-blind clinical trial to compare the efficacy and safety of a multiple amino acid-based ORS with the standard WHO-ORS in the management of non-cholera acute watery diarrhea in infants and young children: “VS002A” trial protocol

Prophylactic abdominal drainage or no drainage after distal pancreatectomy (PANDORINA): a binational multicenter randomized controlled trial

Comparing Sugarbaker versus keyhole mesh technique for open retromuscular parastomal hernia repair: study protocol for a registry-based randomized controlled trial

High-definition transcranial direct current stimulation (HD-tDCS) as augmentation therapy in late-life depression (LLD) with suboptimal response to treatment—a study protocol for a double-blinded randomized sham-controlled trial