Working… Menu

Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03181360
Recruitment Status : Recruiting
First Posted : June 8, 2017
Last Update Posted : April 2, 2019
UiT The Arctic University of Norway
The Royal Norwegian Ministry of Health
Norwegian Health Association
Information provided by (Responsible Party):
University Hospital of North Norway

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.

Condition or disease Intervention/treatment Phase
Ischemic Stroke Stroke, Acute Drug: Tenecteplase Other: Control Phase 3

Detailed Description:


One in five strokes occur during sleep, but patients with "wake-up" stroke are not given thrombolytic therapy because time of stroke onset is unknown. On-going trials are testing alteplase, and use MRI techniques for selection of patients. Tenecteplase has many pharmacological advantages over alteplase: greater fibrin specificity, very rapid action, longer half-life, and single bolus administration. In addition, patient selection based on MRI findings risks excluding many patients that might otherwise benefit. TWIST will test tenecteplase and will not use MRI techniques for selection of patients. Plain CT and CT angiography (if possible) will be performed before randomisation, and CT perfusion will be performed at selected centres, as part of a sub-study.

Study design: TWIST is an international, multi-centre, randomised, open-label, blinded-endpoint trial of tenecteplase for acute ischaemic 'wake-up' stroke.

Study questions:

  1. Can tenecteplase given <4.5 hours of awakening improve functional outcome at 3 months?
  2. Can findings on cerebral plain CT and CT angiography (and CT perfusion, at selected centres) identify patients who benefit from such treatment, compared to other patients?

Patients eligible for treatment who are able to receive tenecteplase within 4.5 hours of waking, will be randomly allocated to treatment with tenecteplase in addition to best standard treatment, versus best standard treatment.

Randomisation and treatment: Central randomisation (over the internet) to tenecteplase 0.25 mg/mg i.v. (maximum dose 25 mg) plus best medical treatment vs. best medical treatment alone.

Imaging: All patients will undergo CT and CT angiography (CTA, if possible) before randomisation and on day 2. CT perfusion (CTP) will be performed at selected centres, as part of a sub-study.

Follow-up and primary effect variable: Centralised follow-up via telephone or mail at 3 months. The primary effect variable is functional outcome (modified Rankin Scale score).

Study size and centers: 500 patients from centers in Norway, Sweden, Denmark, Finland, Estonia, Lithuania, United Kingdom and Switzerland.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST). A Randomised-controlled Trial of Thrombolytic Treatment With Tenecteplase for Acute Ischaemic Stroke Upon Awakening
Actual Study Start Date : June 12, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Tenecteplase
Tenecteplase + Best standard treatment
Drug: 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 Name: Metalyse

No tenecteplase + Best standard treatment
Other: Control
Best standard treatment

Primary Outcome Measures :
  1. Functional outcome at 3 months. [ Time Frame: 3 months ]
    Functional outcome will be assessed by the modified Rankin Scale (mRS), values 0-6

Secondary Outcome Measures :
  1. Symptomatic intracranial haemorrhage during the first 7 days. [ Time Frame: First 7 days ]
    1. Symptoms (neurological deterioration, new headache, new acute hypertension, new nausea or vomiting, or sudden decrease in conscious level).
    2. Intracranial haemorrhage on brain MRI or CT.

  2. Asymptomatic intracranial haemorrhage during the first 7 days. [ Time Frame: First 7 days ]
    Intracranial haemorrhage on brain MRI or CT without: neurological deterioration, new headache, new acute hypertension, new nausea or vomiting or sudden decrease in consciousness level.

  3. Recurrent ischaemic stroke during the first 7 days [ Time Frame: First 7 days ]
    Neurological deterioration (increase of ≥2 on NIHSS, after exclusion of other causes for neurological deterioration) occurring after 72 hours will be considered as a recurrent stroke. A recurrent stroke will be classified as ischaemic if imaging has excluded haemorrhage.

  4. Death from all cause [ Time Frame: First 7 days ]

    Death will be classified according to cause:

    1. Initial stroke
    2. Recurrent stroke
    3. Myocardial infarction
    4. Pneumonia
    5. Other

  5. Death from all cause [ Time Frame: 3 months ]

    Death will be classified according to cause:

    1. Initial stroke
    2. Recurrent stroke
    3. Myocardial infarction
    4. Pneumonia
    5. Other

  6. Barthel Index score [ Time Frame: 3 months ]
    Ordinal scale for measuring performance in activities of daily living

  7. EuroQol Score (EQ-5D) [ Time Frame: 3 months ]
    Measure of health-related quality of life

  8. Mini Mental State Examination [ Time Frame: 3 months ]
    30-point questionnaire for measurement of cognitive impairment

  9. Health-economic variables [ Time Frame: 3 months ]
    Costs related to length of hospital stay, nursing home care after discharge, re-hospitalisations during first 3 months

  10. Functional outcome at 3 months [ Time Frame: 3 months ]
    Functional outcome assessed by dichotomized mRS; values 0-1 vs 2-6.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

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 andexanet) 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03181360

Layout table for location contacts
Contact: Melinda B Roaldsen, MD +47 77627120
Contact: Ellisiv B Mathiesen, MD, PhD +47 77646418

  Hide Study Locations
Layout table for location information
Roskilde Hospital Not yet recruiting
Roskilde, Sjælland, Denmark, 4000
Contact: Troels Wienecke, MD    +45 46 32 32 00    trw@regionsjæ   
Principal Investigator: Troels Wienecke, MD         
Rigshospitalet Not yet recruiting
København, Denmark, 2100
Contact: Helle K Iversen, MD    +45 35 45 35 45   
Bispebjerg hospital Recruiting
København, Denmark, 2400
Contact: Hanne Christensen, MD, PhD    +45 38 63 50 00   
Pärnu Hospital Recruiting
Pärnu, Estonia, 80010
Contact: Katrin Antsov, MD    +3724494800   
Principal Investigator: Katrin Antsov, MD         
East Tallin Central Hospital Recruiting
Tallinn, Estonia, 10138
Contact: Toomas Toomsoo, MD    +3726661900   
Principal Investigator: Toomas Toomsoo, MD         
West Tallin Central Hospital Recruiting
Tallin, Estonia, 10617
Contact: Katrin Gross-Paju, MD    +3726261314   
Principal Investigator: Katrin Gross-Paju, MD         
Tartu University Clinic Recruiting
Tartu, Estonia, 51014
Contact: Janika Kõrv    +372 731 811   
Satakunta Central Hospital Recruiting
Pori, Satakunta, Finland, 28500
Contact: Juha Puustinen, MD    +358262771   
Principal Investigator: Juha Puustinen, MD         
Helsinki University Hospital Recruiting
Helsinki, Finland
Contact: Jukka Putaala, Md, PhD   
Pohjois-Kymen sairaala Recruiting
Kouvola, Finland
Contact: Tero Tapiola    +358 5 352000   
Central Hospital in Vaasa Recruiting
Vaasa, Finland, 65130
Contact: Jukka Saarinen, MD    +35863231111   
Principal Investigator: Jukka Saarinen, MD         
Alytus S. Kudirkos Hospital Recruiting
Alytus, Lithuania, 62114
Contact: Juknelis Kestutis, MD    +37031556301   
Principal Investigator: Juknelis Kestutis, MD         
Lithuanian University of Health Sciences Kauno Klinikos Recruiting
Kaunas, Lithuania, 50009
Contact: Daiva Rastenyte, MD    +37037326467   
Principal Investigator: Daiva Rastenyte, MD         
Klaipeda Seamen's Hospital Recruiting
Klaipėda, Lithuania
Contact: Robertas Urbutis, MD    46 491009 ext +370   
Principal Investigator: Robertas Urbutis, MD         
Republican Vilnius University Hospital Recruiting
Vilnius, Lithuania, LT-04130
Contact: Aleksandras Vilionskis, MD   
Vilnius University Hospital Recruiting
Vilnius, Lithuania, LT-08661
Contact: Dalius Jatuzis, MD, PhD    +370 5 236 5000   
Sørlandet sykehus HF Arendal Recruiting
Arendal, Norway, 4838
Contact: Ragnar Solhoff, MD    03738 ext +47   
Principal Investigator: Ragnar Solhoff, MD         
Drammen sykehus Vestre Viken HF Not yet recruiting
Drammen, Norway, N-3004
Contact: Karl-Friedrich Amthor, MD    +47 91503525   
Principal Investigator: Karl-Friedrich Amthor, MD         
Sørlandet Sykehus HF Flekkefjord Recruiting
Flekkefjord, Norway, N-4400
Contact: Rita Van Lessen, MD    +47 91503738   
Principal Investigator: Rita Van Lessen, MD         
Helse Førde HF Recruiting
Førde, Norway, N-6807
Contact: Magdalena Stankiewicz, MD    +47 57839000   
Principal Investigator: Magdalena Stankiewicz, MD         
Nordlandssykehuset Lofoten Gravdal Recruiting
Gravdal, Norway, N-8372
Contact: Bettina Heermann, MD    +47 76060100   
Principal Investigator: Bettina Heermann, MD         
Helse Finnmark Hammerfest Recruiting
Hammerfest, Norway, N-9601
Contact: Svein A Størdahl, MD    +47 78421000   
Principal Investigator: Svein A Størdahl, MD         
University Hospital of North Norway, Harstad Recruiting
Harstad, Norway, 9480
Contact: Maria Fjellstad, MD    +47 07766   
Principal Investigator: Maria Fjellstad, MD         
Helse Finnmark HF Kirkenes Not yet recruiting
Kirkenes, Norway, N-9900
Contact: Tonje A Melum, MD    +47 78421000   
Principal Investigator: Tonje A Melum, MD         
Sørlandet sykehus Kristiansand HF Recruiting
Kristiansand, Norway, N-4604
Contact: Arnstein Tveiten, MD, PhD    +47 38074000   
Contact: Mary-Helen Søyland, MD    +47 38074000   
Principal Investigator: Arnstein Tveiten, MD, PhD         
Sykehuset Levanger Recruiting
Levanger, Norway, N-7601
Contact: Jens W Horn, MD    +47 74098000   
Principal Investigator: Jens W Horn, MD         
Akershus universitetssykehus (Ahus) Recruiting
Lørenskog, Norway, N-1478
Contact: Antje Reichenbach, MD    +47 91502900   
Principal Investigator: Antje Reichenbach, MD         
Helgelandssykehuset Mosjøen Recruiting
Mosjøen, Norway, N-8651
Contact: Vigdis Ottersen, MD    +47 75115100   
Principal Investigator: Vigdis Ottersen, MD         
University Hospital of North Norway, Narvik Recruiting
Narvik, Norway, N-8504
Contact: Arne Haavik, MD    +47 76968000   
Principal Investigator: Arne Haavik, MD         
Bærum sykehus Vestre Viken HF Recruiting
Sandvika, Norway, N-1346
Contact: Håkon Ihle-Hansen, MD    06780 ext +47   
Principal Investigator: Håkon Ihle-Hansen, MD         
Sykehuset Telemark Skien Recruiting
Skien, Norway, N-3710
Contact: Håkon Tobro, MD    +47 35003500   
Principal Investigator: Håkon Tobro, MD         
Stavanger Universitetssjukehus Recruiting
Stavanger, Norway, N-4068
Contact: Martin W Kurz, MD, PhD    +47 51518052   
Principal Investigator: Martin W Kurz, MD         
University Hospital of North Norway, Tromsø Recruiting
Tromsø, Norway, N-9019
Contact: Linn H Steffensen, MD, PhD    +47 77627125   
Contact: Melinda B Roaldsen, MD    +47 77627120   
Principal Investigator: Linn H Steffensen, MD, PhD         
Sub-Investigator: Ingrid Støen, MD         
St Olavs Hospital Recruiting
Trondheim, Norway, N-7006
Contact: Gitta Rohweder, MD    +47 81555815   
Contact: Bent Indredavik, MD, PhD    +47 81555815   
Principal Investigator: Gitta Rohweder, MD         
Ålesund sjukehus Helse Møre og Romsdal Recruiting
Ålesund, Norway, N-6026
Contact: Yngve M Seljeseth, MD    +47 70105000   
Principal Investigator: Yngve M Seljeseth, MD         
Sahlgrenska Universitetssjukhuset Recruiting
Göteborg, Sweden, 413 45
Contact: Jan-Erik Karlsson, MD    +46 31 342 10 00   
Hässleholm Sjukhus Recruiting
Hässleholm, Sweden, 281 25
Contact: Magnus Esbjörnsson, MD    +46 0451 29 60 60   
Central Hospital Karlstad Recruiting
Karlstad, Sweden, 65230
Contact: Felix Andler, MD    +4654615000   
Principal Investigator: Felix Andler, MD         
Skåne Universitetssjukhus Recruiting
Malmö, Sweden, 221 85
Contact: Jesper Petersson, MD, PhD    +46 40331000   
Skaraborg Hospital Skövde Recruiting
Skövde, Sweden, 541 85
Contact: Björn Cederin, MD    +46500431000   
Principal Investigator: Björn Cederin, MD         
Karolinska sjukhuset Recruiting
Solna, Sweden, 171 76
Contact: Erik Lundström, MD, PhD    +46 8 517 700 00   
Saint Göran Hospital Not yet recruiting
Stockholm, Sweden, 112 81
Contact: Jan Mathé, MD    +46858701000   
Principal Investigator: Jan Mathé, MD         
Danderyd Hospital Recruiting
Stockholm, Sweden, 18288
Contact: Elisabet Rooth, MD    +46812355000   
Principal Investigator: Elisabet Rooth, MD         
Akademiska Sjukhuset Recruiting
Uppsala, Sweden, 751 85
Contact: Karl Sjölin, MD    +46 18 611 00 00   
Ängelholm Hospital Recruiting
Ängelholm, Sweden, 26281
Contact: Björn Hedström, MD    +4643181000   
Principal Investigator: Björn Hedström, MD         
University Hospital Basel Recruiting
Basel, Switzerland, 4031
Contact: Gian M De Marchis, MD, MSc    +41 61 265 25 25   
United Kingdom
Pinderfields Hospital Recruiting
Wakefield, Mid Yorkshire, United Kingdom, WF1 4DG
Contact: Michael Carpenter, MD    48118110 ext +4484   
Principal Investigator: Michael Carpenter, MD         
Yeovil District Hospital Recruiting
Yeovil, Somerset, United Kingdom, BA21 4AT
Contact: Khalid Rashed, MD    35475122 ext +4419   
Principal Investigator: Khalid Rashed, MD         
Aberdeen Royal Infirmary Not yet recruiting
Aberdeen, United Kingdom, AB25 2ZN
Contact: Mary Joan Macleod, MD    +44 345 456 6000   
Principal Investigator: Mary Joan Macleod, MD         
Royal Bournemoth and Christchurch Hospital Not yet recruiting
Bournemouth, United Kingdom, BH7 7DW
Contact: Oliver Hopper, MD    +441202 303626   
Principal Investigator: Oliver Hopper, MD         
Addenbrookes Hospital Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Elizabeth Warburton, MD    +44 1223 245151   
Principal Investigator: Elizabeth Warburton, MD         
Countess of Chester Hospital NHS Foundation Trust Recruiting
Chester, United Kingdom, CH2 1UL
Contact: Kausik Chatterjee    44365000 ext +4412   
Principal Investigator: Kausik Chatterjee, MD         
Royal Derby Hospital Recruiting
Derby, United Kingdom, DE 22 3 NE
Contact: Timothy England, MD    +441332340131   
Principal Investigator: Timothy England, MD         
Royal Infirmary of Edinburgh Hospital Not yet recruiting
Edinburgh, United Kingdom, EH16 4SA
Contact: William Whiteley, MD    +44 131 536 1000   
Principal Investigator: William Whiteley, MD         
Royal Devon and Exeter Hospital Recruiting
Exeter, United Kingdom, EX2 5DW
Contact: Martin James, MD    +44 1392 411611   
Principal Investigator: Martin James, MD         
Leicester Royal Infirmary Recruiting
Leicester, United Kingdom, LE1 5WW
Contact: Thompson G Robinson, MD, PhD   
Contact: Lisa Manning, MD   
University College London Recruiting
London, United Kingdom, NW1 2BU
Contact: Richard Perry, MD    +44 20 3456 7890   
Principal Investigator: Richard Perry, MD         
King´s College Hospital Recruiting
London, United Kingdom, SE5 9RS
Contact: Lalit Kalra, MD    +44 20 3299 9000   
Principal Investigator: Lalit Kalra, MD         
St Georges Hospital Recruiting
London, United Kingdom, SW17 0QT
Contact: Barry Moynihan, MD    +44 20 8672 1255   
Principal Investigator: Barry Moynihan, MD         
Charing Cross Hospital Recruiting
London, United Kingdom, W6 8RF
Contact: Omid Halse, MD    +44 20 3311 1234   
Principal Investigator: Omid Halse, MD         
Morriston Hospital Not yet recruiting
Morriston, United Kingdom, SA6 6NL
Contact: Mushtaq Wani, MD    +44 1792 702222   
Principal Investigator: Mushtaq Wani, MD         
Royal Victoria Infirmary Not yet recruiting
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Contact: Anand Dixit, MD    +441912336161   
Principal Investigator: Anand Dixit, MD         
Nottingham City Hospital Recruiting
Nottingham, United Kingdom, NG5 1PB
Contact: Philip Bath, MD    +441159691169   
Principal Investigator: Philip Bath, MD         
Yeovil District Hospital Not yet recruiting
Yeovil, United Kingdom, BA21 4AT
Contact: Khalid Rashed, MD    +44 1935 475122   
Principal Investigator: Khalid Rashed, MD         
Sponsors and Collaborators
University Hospital of North Norway
UiT The Arctic University of Norway
The Royal Norwegian Ministry of Health
Norwegian Health Association
Layout table for investigator information
Study Chair: Eivind Berge, MD, PhD UiT The Arctic University of Norway
Principal Investigator: Ellisiv B Mathiesen University Hospital of North Norway
  Study Documents (Full-Text)

Documents provided by University Hospital of North Norway:

Layout table for additonal information
Responsible Party: University Hospital of North Norway Identifier: NCT03181360     History of Changes
Other Study ID Numbers: 2015/1070/REC North
2014-000096-80 ( EudraCT Number )
First Posted: June 8, 2017    Key Record Dates
Last Update Posted: April 2, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital of North Norway:
ischemic stroke
computed tomography
Additional relevant MeSH terms:
Layout table for MeSH terms
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action