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

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

doi:10.1186/s13063-022-06301-0

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

Trials. 2022 May 19;23(1):421. doi: 10.1186/s13063-022-06301-0.

Authors

Agnethe Eltoft^{1

2}, Tom Wilsgaard³, Melinda B Roaldsen^{4

5}, Mary-Helen Søyland^{4

6}, Erik Lundström⁷, Jesper Petersson⁸, Bent Indredavik^{9

10}, Jukka Putaala¹¹, Hanne Christensen¹², Janika Kõrv¹³, Dalius Jatužis¹⁴, Stefan T Engelter^{15

16}, Gian Marco De Marchis¹⁵, David J Werring¹⁷, Thompson Robinson¹⁸, Arnstein Tveiten⁶, Ellisiv B Mathiesen^{19

4}

Affiliations

¹ Department of Neurology, University Hospital of North Norway, Tromsø, Norway. agnethe.eltoft@unn.no.
² Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway. agnethe.eltoft@unn.no.
³ Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
⁴ Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
⁵ Department of Clinical Research, University Hospital of North Norway, Tromsø, Norway.
⁶ Department of Neurology, Sorlandet Hospital Kristiansand, Kristiansand, Norway.
⁷ Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
⁸ Department of Neurology, Skåne University Hospital, Malmö, Sweden.
⁹ Department of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
¹⁰ Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
¹¹ Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹² Department of Neurology, Bispebjerg Hospital and University of Copenhagen, Copenhagen, Denmark.
¹³ Department of Neurology and Neurosurgery, University of Tartu and Tartu University Hospital, Tartu, Estonia.
¹⁴ Department of Neurology and Neurosurgery, Center for Neurology, Vilnius University, Vilnius, Lithuania.
¹⁵ Department of Neurology, University Hospital of Basel and University of Basel, Basel, Switzerland.
¹⁶ Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland.
¹⁷ Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
¹⁸ College of Life Sciences and NIHR Biomedical Research Centre, University of Leicester, Leicester, UK.
¹⁹ Department of Neurology, University Hospital of North Norway, Tromsø, Norway.

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.gov NCT03181360 . EudraCT Number 2014-000096-80 . WHO ICRTP registry number ISRCTN10601890 .

Keywords: Acute stroke therapy; Ischemic stroke; TWIST; Tenecteplase; Thrombolysis; Wake-up stroke.

Publication types

Randomized Controlled Trial

MeSH terms

Brain Ischemia* / diagnostic imaging
Brain Ischemia* / drug therapy
Fibrinolytic Agents / adverse effects
Humans
Ischemic Stroke*
Stroke* / diagnostic imaging
Stroke* / drug therapy
Tenecteplase / adverse effects
Thrombolytic Therapy
Tissue Plasminogen Activator / adverse effects
Treatment Outcome

Substances

Fibrinolytic Agents
Tissue Plasminogen Activator
Tenecteplase

Associated data

ClinicalTrials.gov/NCT03181360

Grants and funding

CS/17/5/32826/BHF_/British Heart Foundation/United Kingdom