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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03181360




Registration number
NCT03181360
Ethics application status
Date submitted
6/06/2017
Date registered
8/06/2017
Date last updated
14/05/2021

Titles & IDs
Public title
Tenecteplase in Wake-up Ischaemic Stroke Trial
Scientific title
Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST). A Randomised-controlled Trial of Thrombolytic Treatment With Tenecteplase for Acute Ischaemic Stroke Upon Awakening
Secondary ID [1] 0 0
2014-000096-80
Secondary ID [2] 0 0
2015/1070/REC North
Universal Trial Number (UTN)
Trial acronym
TWIST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischemic Stroke 0 0
Stroke, Acute 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic
Neurological 0 0 0 0
Other neurological disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tenecteplase
Other interventions - Control

Active comparator: Tenecteplase - Tenecteplase + Best standard treatment

Other: Control - No tenecteplase + Best standard treatment


Treatment: Drugs: Tenecteplase
Single dose intravenous injection of recombinant fibrin-specific tissue plasminogen activator (tenecteplase) 0.25 mg (200 IU) per kg body weight up to a maximum of 25 mg (5000 IU), given as a bolus over approx. 10 seconds.

Other interventions: Control
Best standard treatment
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Functional outcome at 3 months.
Timepoint [1] 0 0
3 months
Secondary outcome [1] 0 0
Symptomatic intracranial haemorrhage during the first 7 days.
Timepoint [1] 0 0
First 7 days
Secondary outcome [2] 0 0
Asymptomatic intracranial haemorrhage during the first 7 days.
Timepoint [2] 0 0
First 7 days
Secondary outcome [3] 0 0
Recurrent ischaemic stroke during the first 7 days
Timepoint [3] 0 0
First 7 days
Secondary outcome [4] 0 0
Death from all cause
Timepoint [4] 0 0
First 7 days
Secondary outcome [5] 0 0
Death from all cause
Timepoint [5] 0 0
3 months
Secondary outcome [6] 0 0
Barthel Index score
Timepoint [6] 0 0
3 months
Secondary outcome [7] 0 0
EuroQol Score (EQ-5D)
Timepoint [7] 0 0
3 months
Secondary outcome [8] 0 0
Mini Mental State Examination
Timepoint [8] 0 0
3 months
Secondary outcome [9] 0 0
Health-economic variables
Timepoint [9] 0 0
3 months
Secondary outcome [10] 0 0
Functional outcome at 3 months
Timepoint [10] 0 0
3 months

Eligibility
Key inclusion criteria
* Stroke symptoms on awakening that were not present before sleep
* Clinical diagnosis of stroke with limb weakness with NIHSS score >=3, or dysphasia
* Treatment with tenecteplase is possible within 4.5 hours of awakening
* Written consent from the patient, non-written consent from the patient (witnessed by non-participating health care personnel), or written consent from the nearest family member
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Age <18 years
* NIHSS score >25 or NIHSS consciousness score >2, or seizures during stroke onset
* Findings on plain CT that indicate that the patient is unlikely to benefit from treatment:

* Infarction comprising more than >1/3 of the middle cerebral artery territory on plain CT or CT perfusion
* Intracranial haemorrhage, structural brain lesions which can mimic stroke (e.g cerebral tumour)
* Active internal bleeding of high risk of bleeding, e.g.:

* Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days
* Any known defect in coagulation, e.g. current use of vitamin K antagonist with an INR >1.7 or prothrombin time >15 seconds, or use of direct thrombin inhibitors or direct factor Xa inhibitors during the last 24 hours (unless reversal of effect can be achieved by agents such as idarucizumab) or with elevated sensitive laboratory tests (such as activated partial thromboplastin time (aPTT), international normalized ratio (INR), platelet count, ecarin clotting time, thrombin time (TT), or appropriate factor Xa activity assays), or heparins during the last 24 hours or with an elevated aPTT greater than the upper limit of normal
* Known defect of clotting or platelet function or platelet count below 100,000/mm3 (but patients on antiplatelet agents can be included)
* Ischaemic stroke or myocardial infarction in previous 3 months, previous intracranial haemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm, arteriovenous malformation or aneurysm
* Contraindications to tenecteplase, e.g., acute bacterial endocarditis or pericarditis; acute pancreatitis; severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension; active hepatitis; systemic cancer with increased bleeding risk; haemostatic defect including secondary to severe hepatic, renal disease; organ biopsy; prolonged cardiopulmonary resuscitation > 2 min (within 2 weeks)
* Persistent blood pressure elevation (systolic =185 mmHg or diastolic =110 mmHg), despite blood pressure lowering treatment
* Blood glucose <2.7 or >20.0 mmol/L (use of finger-stick measurement devices is acceptable)
* Pregnancy, positive pregnancy test, childbirth during last 10 days, or breastfeeding. In any woman of childbearing potential, a pregnancy test must be performed and the result assessed before trial entry
* Other serious or life-threatening disease before the stroke: severe mental or physical disability (e.g. Mini Mental Status score <20, or mRS score =3), or life expectancy less than 12 months
* Patient unavailability for follow-up (e.g. no fixed address)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2022
Actual
Sample size
Target
600
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
Denmark
State/province [2] 0 0
København
Country [3] 0 0
Denmark
State/province [3] 0 0
Odense
Country [4] 0 0
Estonia
State/province [4] 0 0
Pärnu
Country [5] 0 0
Estonia
State/province [5] 0 0
Tallinn
Country [6] 0 0
Estonia
State/province [6] 0 0
Tallin
Country [7] 0 0
Estonia
State/province [7] 0 0
Tartu
Country [8] 0 0
Finland
State/province [8] 0 0
Satakunta
Country [9] 0 0
Finland
State/province [9] 0 0
Helsinki
Country [10] 0 0
Finland
State/province [10] 0 0
Joensuu
Country [11] 0 0
Finland
State/province [11] 0 0
Kouvola
Country [12] 0 0
Finland
State/province [12] 0 0
Vaasa
Country [13] 0 0
Latvia
State/province [13] 0 0
Riga
Country [14] 0 0
Lithuania
State/province [14] 0 0
Alytus
Country [15] 0 0
Lithuania
State/province [15] 0 0
Kaunas
Country [16] 0 0
Lithuania
State/province [16] 0 0
Klaipeda
Country [17] 0 0
Lithuania
State/province [17] 0 0
Vilnius
Country [18] 0 0
New Zealand
State/province [18] 0 0
Christchurch
Country [19] 0 0
Norway
State/province [19] 0 0
Arendal
Country [20] 0 0
Norway
State/province [20] 0 0
Drammen
Country [21] 0 0
Norway
State/province [21] 0 0
Flekkefjord
Country [22] 0 0
Norway
State/province [22] 0 0
Førde
Country [23] 0 0
Norway
State/province [23] 0 0
Gravdal
Country [24] 0 0
Norway
State/province [24] 0 0
Hammerfest
Country [25] 0 0
Norway
State/province [25] 0 0
Harstad
Country [26] 0 0
Norway
State/province [26] 0 0
Kirkenes
Country [27] 0 0
Norway
State/province [27] 0 0
Kristiansand
Country [28] 0 0
Norway
State/province [28] 0 0
Levanger
Country [29] 0 0
Norway
State/province [29] 0 0
Lørenskog
Country [30] 0 0
Norway
State/province [30] 0 0
Mosjøen
Country [31] 0 0
Norway
State/province [31] 0 0
Narvik
Country [32] 0 0
Norway
State/province [32] 0 0
Sandvika
Country [33] 0 0
Norway
State/province [33] 0 0
Skien
Country [34] 0 0
Norway
State/province [34] 0 0
Stavanger
Country [35] 0 0
Norway
State/province [35] 0 0
Tromsø
Country [36] 0 0
Norway
State/province [36] 0 0
Trondheim
Country [37] 0 0
Norway
State/province [37] 0 0
Ålesund
Country [38] 0 0
Sweden
State/province [38] 0 0
Göteborg
Country [39] 0 0
Sweden
State/province [39] 0 0
Hässleholm
Country [40] 0 0
Sweden
State/province [40] 0 0
Karlstad
Country [41] 0 0
Sweden
State/province [41] 0 0
Lund
Country [42] 0 0
Sweden
State/province [42] 0 0
Malmö
Country [43] 0 0
Sweden
State/province [43] 0 0
Skövde
Country [44] 0 0
Sweden
State/province [44] 0 0
Solna
Country [45] 0 0
Sweden
State/province [45] 0 0
Stockholm
Country [46] 0 0
Sweden
State/province [46] 0 0
Uppsala
Country [47] 0 0
Sweden
State/province [47] 0 0
Ängelholm
Country [48] 0 0
Switzerland
State/province [48] 0 0
Basel
Country [49] 0 0
Switzerland
State/province [49] 0 0
Nyon
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Mid Yorkshire
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Northumberland
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Aberdeen
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Birkenhead
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Birmingham
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Bournemouth
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Cambridge
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Chester
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Coventry
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Derby
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Edinburgh
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Exeter
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Gloucester
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Halifax
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Kingston upon Hull
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Leeds
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Leicester
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Liverpool
Country [68] 0 0
United Kingdom
State/province [68] 0 0
London
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Luton
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Morriston
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Newcastle Upon Tyne
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Nottingham
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Salford
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Southampton
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Stoke-on-Trent
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Taunton
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Yeovil

Funding & Sponsors
Primary sponsor type
Other
Name
University Hospital of North Norway
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
UiT The Arctic University of Norway
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The Royal Norwegian Ministry of Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Norwegian Health Association
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Stroke is a leading causes of death and disability. At least 20% of strokes occur during sleep, so- called 'wake up stroke'. Thrombolysis with the clot-busting drug alteplase is effective for acute ischaemic stroke, provided that it is given within 4.5 hours of symptom onset. Patients with wake-up stroke are currently ineligible for clot-busting therapy. Previous studies indicate that many wake-up strokes occur just before awakening.

In this study, patients with wake-up stroke will be randomized to thrombolysis with tenecteplase and best standard treatment or to best standard treatment without thrombolysis. Tenecteplase has several potential advantages over alteplase, including very rapid action and that it can be given as a single injection. Prior to thrombolysis, a brain scan must be done to exclude bleeding or significant brain damage as a result from the stroke. We will use a CT scan to inform this decision. CT is used as a routine examination in all stroke patients. Other studies testing clot-busting treatment in wake-up stroke are using alteplase and more complex brain scans, which are not routinely available in the emergency situation in all hospitals.
Trial website
https://clinicaltrials.gov/study/NCT03181360
Trial related presentations / publications
Eltoft A, Wilsgaard T, Roaldsen MB, Soyland MH, Lundstrom E, Petersson J, Indredavik B, Putaala J, Christensen H, Korv J, Jatuzis D, Engelter ST, De Marchis GM, Werring DJ, Robinson T, Tveiten A, Mathiesen EB. 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.
Roaldsen MB, Lindekleiv H, Eltoft A, Jusufovic M, Soyland MH, Petersson J, Indredavik B, Tveiten A, Putaala J, Christensen H, Korv J, Jatuzis D, Engelter ST, Marco De Marchis G, Wilsgaard T, Werring DJ, Robinson T, Mathiesen EB, Berge E. Tenecteplase in wake-up ischemic stroke trial: Protocol for a randomized-controlled trial. Int J Stroke. 2021 Oct;16(8):990-994. doi: 10.1177/1747493020984073. Epub 2021 Jan 14. Erratum In: Int J Stroke. 2021 Dec;16(9):NP1. doi: 10.1177/1747493021995410.
Public notes

Contacts
Principal investigator
Name 0 0
Ellisiv B Mathiesen
Address 0 0
University Hospital of North Norway
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Melinda B Roaldsen, MD
Address 0 0
Country 0 0
Phone 0 0
+47 77627120
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03181360