Tenecteplase in Wake-up Ischaemic Stroke Trial

NCT03181360 | Unknown Phase 3 DMC FDA Drug

• 2 other identifiers: 2015/1070/REC North2014-000096-80
• Study Type: interventional
• Target: 600
• Locations: 11 countries
• Sites: 83

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.

Conditions

Ischemic Stroke; Stroke, Acute

Keywords

ischemic stroke; wake-up; thrombolysis; tenecteplase; computed tomography

Outcome Measures

Primary Outcomes (1)

• Functional outcome at 3 months.

  Functional outcome will be assessed by the modified Rankin Scale (mRS), values 0-6

  3 months

Secondary Outcomes (10)

• Symptomatic intracranial haemorrhage during the first 7 days.

  First 7 days

• Asymptomatic intracranial haemorrhage during the first 7 days.

  First 7 days

• Recurrent ischaemic stroke during the first 7 days

  First 7 days

• Death from all cause

  First 7 days

• Death from all cause

  3 months

Study Arms (2)

Tenecteplase

ACTIVE COMPARATOR

Tenecteplase + Best standard treatment

Drug: Tenecteplase

Control

OTHER

No tenecteplase + Best standard treatment

Other: Control

Interventions

Tenecteplase DRUG

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.

Also known as: Metalyse

Tenecteplase

Control OTHER

Best standard treatment

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital of North Norway: lead
• UiT The Arctic University of Norway: collaborator
• The Royal Norwegian Ministry of Health: collaborator
• Norwegian Health Association: collaborator

Study Sites (83)

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

NOT YET RECRUITING

Bispebjerg hospital

Copenhagen, 2400, Denmark

RECRUITING

Odense University Hospital

Odense, Denmark

RECRUITING

Pärnu Hospital

Pärnu, 80010, Estonia

RECRUITING

East Tallin Central Hospital

Tallinn, 10138, Estonia

RECRUITING

West Tallin Central Hospital

Tallinn, 10617, Estonia

RECRUITING

Tartu University Clinic

Tartu, 51014, Estonia

RECRUITING

Satakunta Central Hospital

Pori, Satakunta, 28500, Finland

RECRUITING

Helsinki University Hospital

Helsinki, Finland

RECRUITING

Siun sote - Joint municipal authority for North Karelia social and health services

Joensuu, Finland

RECRUITING

Pohjois-Kymen sairaala

Kouvola, Finland

RECRUITING

Central Hospital in Vaasa

Vaasa, 65130, Finland

RECRUITING

Riga East University Hospital

Riga, Latvia

NOT YET RECRUITING

Alytus S. Kudirkos Hospital

Alytus, 62114, Lithuania

RECRUITING

Lithuanian University of Health Sciences Kauno Klinikos

Kaunas, 50009, Lithuania

RECRUITING

Klaipeda Seamen's Hospital

Klaipėda, Lithuania

RECRUITING

Republican Vilnius University Hospital

Vilnius, LT-04130, Lithuania

RECRUITING

Vilnius University Hospital

Vilnius, LT-08661, Lithuania

RECRUITING

Christchurch Hospital

Christchurch, New Zealand

RECRUITING

Sørlandet sykehus HF Arendal

Arendal, 4838, Norway

TERMINATED

Ålesund sjukehus Helse Møre og Romsdal

Ålesund, N-6026, Norway

RECRUITING

Drammen sykehus Vestre Viken HF

Drammen, N-3004, Norway

NOT YET RECRUITING

Sørlandet Sykehus HF Flekkefjord

Flekkefjord, N-4400, Norway

RECRUITING

Helse Førde HF

Førde, N-6807, Norway

RECRUITING

Nordlandssykehuset Lofoten Gravdal

Gravdal, N-8372, Norway

RECRUITING

Helse Finnmark Hammerfest

Hammerfest, N-9601, Norway

RECRUITING

University Hospital of North Norway, Harstad

Harstad, 9480, Norway

RECRUITING

Helse Finnmark HF Kirkenes

Kirkenes, N-9900, Norway

NOT YET RECRUITING

Sørlandet sykehus Kristiansand HF

Kristiansand, N-4604, Norway

RECRUITING

Sykehuset Levanger

Levanger, N-7601, Norway

TERMINATED

Akershus universitetssykehus (Ahus)

Lørenskog, N-1478, Norway

RECRUITING

Helgelandssykehuset Mosjøen

Mosjøen, N-8651, Norway

WITHDRAWN

University Hospital of North Norway, Narvik

Narvik, N-8504, Norway

RECRUITING

Bærum sykehus Vestre Viken HF

Sandvika, N-1346, Norway

RECRUITING

Sykehuset Telemark Skien

Skien, N-3710, Norway

RECRUITING

Stavanger Universitetssjukehus

Stavanger, N-4068, Norway

ACTIVE NOT RECRUITING

University Hospital of North Norway, Tromsø

Tromsø, N-9019, Norway

RECRUITING

St Olavs Hospital

Trondheim, N-7006, Norway

RECRUITING

Ängelholm Hospital

Ängelholm, 26281, Sweden

RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, 413 45, Sweden

RECRUITING

Hässleholm Sjukhus

Hässleholm, 281 25, Sweden

RECRUITING

Central Hospital Karlstad

Karlstad, 65230, Sweden

RECRUITING

Skåne University Hospital Lund

Lund, Sweden

NOT YET RECRUITING

Skåne University Hospital Malmö

Malmo, 221 85, Sweden

RECRUITING

Skaraborg Hospital Skövde

Skövde, 541 85, Sweden

RECRUITING

Karolinska sjukhuset

Solna, 171 76, Sweden

WITHDRAWN

Saint Göran Hospital

Stockholm, 112 81, Sweden

NOT YET RECRUITING

Danderyd Hospital

Stockholm, 18288, Sweden

RECRUITING

Akademiska Sjukhuset

Uppsala, 751 85, Sweden

RECRUITING

University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

Groupement Hospitalier Ouest Lémanique

Nyon, Switzerland

RECRUITING

Pinderfields Hospital

Wakefield, Mid Yorkshire, WF1 4DG, United Kingdom

RECRUITING

Northumbria Specialist Emergency Care Hospital

Cramlington, Northumberland, United Kingdom

NOT YET RECRUITING

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

NOT YET RECRUITING

Arrowe Park

Birkenhead, United Kingdom

RECRUITING

University Hospital Birmingham

Birmingham, United Kingdom

RECRUITING

Royal Bournemoth and Christchurch Hospital

Bournemouth, BH7 7DW, United Kingdom

NOT YET RECRUITING

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Countess of Chester Hospital NHS Foundation Trust

Chester, CH2 1UL, United Kingdom

RECRUITING

University Hospitals Coventry & Warwickshire

Coventry, United Kingdom

RECRUITING

Royal Derby Hospital

Derby, DE 22 3 NE, United Kingdom

RECRUITING

Royal Infirmary of Edinburgh Hospital

Edinburgh, EH16 4SA, United Kingdom

NOT YET RECRUITING

Royal Devon and Exeter Hospital

Exeter, EX2 5DW, United Kingdom

RECRUITING

Gloucestershire Royal Hospital

Gloucester, United Kingdom

RECRUITING

Calderdale Royal Infirmary

Halifax, United Kingdom

RECRUITING

Hull University Teaching Hospital

Hull, United Kingdom

RECRUITING

Leeds General Infirmary

Leeds, United Kingdom

RECRUITING

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

RECRUITING

Royal Liverpool University Hospital

Liverpool, United Kingdom

NOT YET RECRUITING

University College London

London, NW1 2BU, United Kingdom

RECRUITING

King´s College Hospital

London, SE5 9RS, United Kingdom

RECRUITING

St Georges Hospital

London, SW17 0QT, United Kingdom

RECRUITING

Charing Cross Hospital

London, W6 8RF, United Kingdom

RECRUITING

Royal London Hospital

London, United Kingdom

RECRUITING

Luton and Dunstable University Hospital

Luton, United Kingdom

RECRUITING

Morriston Hospital

Morriston, SA6 6NL, United Kingdom

RECRUITING

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

RECRUITING

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

RECRUITING

Salford Royal Hospital

Salford, United Kingdom

RECRUITING

Southhampton General Hospital

Southampton, United Kingdom

RECRUITING

Royal Stoke University Hospital

Stoke-on-Trent, United Kingdom

RECRUITING

Musgrove Park Hospital

Taunton, United Kingdom

RECRUITING

Yeovil District Hospital

Yeovil, BA21 4AT, United Kingdom

RECRUITING

Related Publications (3)

• Roaldsen MB, Eltoft A, Wilsgaard T, Christensen H, Engelter ST, Indredavik B, Jatuzis D, Karelis G, Korv J, Lundstrom E, Petersson J, Putaala J, Soyland MH, Tveiten A, Bivard A, Johnsen SH, Mazya MV, Werring DJ, Wu TY, De Marchis GM, Robinson TG, Mathiesen EB; TWIST Investigators. Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2023 Feb;22(2):117-126. doi: 10.1016/S1474-4422(22)00484-7. Epub 2022 Dec 19.

  PMID: 36549308 DERIVED

• 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.

  PMID: 35590386 DERIVED

• 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.

  PMID: 33446083 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Ellisiv B Mathiesen

  University Hospital of North Norway

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melinda B Roaldsen, MD

CONTACT

+47 77627120; melinda.b.roaldsen@uit.no

Agnethe Eltoft, MD, PhD

CONTACT

+47 77698906; agnethe.eltoft@unn.no

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2017
• First Posted: June 8, 2017
• Study Start: June 12, 2017
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2022
• Last Updated: May 14, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1); ES (4); NO (19); LA (1); GB (32); SE (11); DK (2); CH (2); FI (5); LI (5); US (1)