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Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke (WAKE-UP)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01525290
First Posted: February 2, 2012
Last Update Posted: July 19, 2017
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. Read our disclaimer for details.
Information provided by (Responsible Party):
Götz Thomalla, MD, Universitätsklinikum Hamburg-Eppendorf
  Purpose
WAKE-UP is an investigator initiated European multicenter randomized controlled clinical trial of MRI based thrombolysis in acute stroke patients with unknown time of symptom onset, e.g. due to recognition of stroke symptoms on awakening. Objective of WAKE-UP is to prove efficacy and safety of MRI-based intravenous thrombolysis with Alteplase in patients waking up with stroke symptoms or patients with otherwise unknown symptom onset.

Condition Intervention Phase
Stroke Drug: Alteplase Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke: a Randomised, Double-blind, Placebo-controlled Trial

Resource links provided by NLM:


Further study details as provided by Götz Thomalla, MD, Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:
  • Efficacy [ Time Frame: 90 day after stroke ]
    Favourable outcome (Modified Rankin Scale 0-1)

  • Safety [ Time Frame: 90 day after stroke ]
    • Mortality
    • Death or dependency (Modified Rankin Scale 4-6)


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 90 days after stroke ]
    • Global outcome score
    • Responder analysis (Modified Rankin Scale 0, 0-1 or 0-2 depending on severity of symptoms assessed by the National Institutes of Health Stroke Scale on admission)
    • Outcome across all disability ranges (categorical shift in Modified Rankin Scale score)
    • Infarct volume (measured 22-36 hours after treatment)
    • Functional health status and quality of life
    • Use of health care system resources

  • Safety [ Time Frame: 90 days after stroke ]
    • Symptomatic intracranial haemorrhage (SICH) as defined in SITS-MOST
    • SICH as defined ECASS II
    • SICH as defined in NINDS
    • Parenchymal haemorrhage type 2 (PH-2)


Enrollment: 501
Study Start Date: September 2012
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: intravenous tissue plasminogen activator
Intervention drug: intravenous tissue plasminogen activator (tPA), alteplase
Drug: Alteplase
Intravenous tissue plasminogen activator (Alteplase) 0.9 mg/kg body-weight up to a maximum of 90 mg, 10% as bolus, 90% over 1 hour as infusion
Other Names:
  • Actilyse
  • Activase
  • rt-PA
Placebo Comparator: Placebo
Intervention drug: placebo
Drug: Placebo
lyophilised powder to be reconstituted as solution indistinguishable from the active drug

Detailed Description:

WAKE-UP is a clinical trial of MRI based thrombolysis in acute stroke patients with unknown time of symptom onset, e.g. due to recognition of stroke symptoms on awakening. Intravenous thrombolysis with Alteplase is available as effective and safe treatment of acute stroke within 4.5 hours of symptom onset. However, in about 20% of acute stroke patients time of symptom onset is unknown. This large group of patients is currently excluded from treatment with Alteplase. The objective of the research proposed in the WAKE-UP project is to provide effective treatment options for this large group of acute stroke patients.

WAKE-UP is designed to prove efficacy and safety of MRI-based intravenous thrombolysis with Alteplase in patients waking up with stroke symptoms or patients with otherwise unknown symptom onset. Patients will be enrolled based on MRI findings indicative of acute ischemic stroke less than 4.5 hours of age.

  Eligibility

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Clinical Inclusion Criteria

  • Clinical diagnosis of acute ischemic stroke with unknown symptom onset (e.g., stroke symptoms recognized on awakening)
  • Last known well (without neurological symptoms) > 4.5 hours of treatment initiation
  • Measurable disabling neurological deficit (defined as an impairment of one or more of the following: language, motor function, cognition, gaze, vision, neglect)
  • Age 18-80 years
  • Treatment can be started within 4.5 hours of symptom recognition (e.g., awakening)
  • Written informed consent by patient or proxy

Imaging Inclusion Criteria:

  • Acute stroke MRI including diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) completed
  • MRI showing a pattern of "DWI-FLAIR-mismatch", i.e. acute ischemic lesion visibly on DWI ("positive DWI") but no marked parenchymal hyperintensity visible on FLAIR ("negative FLAIR") indicative of an acute ischemic lesion ≤4.5 hours of age

Exclusion Criteria:

Clinical Exclusion Criteria

  • Planned or anticipated treatment with endovascular reperfusion strategies (e.g. intra-arterial thrombolysis, mechanical recanalization techniques)
  • Pre-stroke disability (inability to carry out all daily activities, requiring some help or supervision, i.e. slight disability corresponding to an MRS score > 1)
  • Participation in any investigational study in the previous 30 days
  • Severe stroke by clinical assessment (e.g. NIHSS > 25)
  • Hypersensitivity to Alteplase or any of the excipients
  • Pregnancy or lactating (formal testing needed in woman of childbearing potential; childbearing potential is assumed in women up to 55 years of age)
  • Significant bleeding disorder at present or within past 6 months
  • Known haemorrhagic diathesis
  • Manifest or recent severe or dangerous bleeding
  • Known history of or suspected intracranial haemorrhage
  • Suspected subarachnoid haemorrhage (even if CT is negative) or condition after subarachnoid haemorrhage from aneurysm
  • History of CNS damage (e.g. neoplasm, aneurysm, intracranial or spinal surgery)
  • Recent (within 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel
  • Current use of anticoagulants (e.g. Phenprocoumon, Warfarin, new anticoagulants such as Dabigatran) or current use of heparin and elevated thromboplastin time (low-dose subcutaneous heparin is allowed)
  • Platelet count < 100.000/mm3 (<100G/l)
  • Blood glucose < 50 or > 400 mg/dl (< 2.8 or 22.2 mmol/l)
  • Severe uncontrolled hypertension, i.e. systolic blood pressure > 185 mmHg or diastolic blood pressure >110 mmHg or requiring aggressive medication to maintain blood pressure within these limits (routine medical treatment is allowed to lower the blood pressure below these limits)
  • Manifest or recent bacterial endocarditis, pericarditis
  • Manifest or recent acute pancreatitis
  • Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial aneurysm, arterial/venous malformations
  • Neoplasm with increased bleeding risk
  • Manifest severe liver disease including hepatic failure, cirrhosis, portal hypertension and active hepatitis
  • Major surgery or significant trauma in past 3 months
  • Stroke within 30 days
  • Life expectancy 6 months or less by judgement of the investigator
  • Any condition associated with a significantly increased risk of severe bleeding not mentioned above
  • Any contraindication to MRI (e.g. cardiac pacemaker)

Imaging Exclusion Criteria:

  • Poor MRI quality precluding interpretation according to the study protocol
  • Any sign of intracranial haemorrhage on baseline MRI
  • FLAIR showing a marked parenchymal hyperintensity in a region corresponding to the acute DWI lesion indicative of an acute ischemic lesion with a high likelihood of being > 4.5 hours old
  • Large DWI lesion volume > 1/3 of the MCA or > 50% of the anterior cerebral artery (ACA) or posterior cerebral artery (PCA) territory (visual inspection) or > 100 ml
  • Any MRI findings indicative of a high risk of symptomatic intracranial haemorrhage related to potential IV-tPA treatment in the judgement of the investigator
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT01525290


Locations
Belgium
Katholieke Universitet Leuven
Leuven, Belgium, 3000
Denmark
Aarhus Universitetshospital, Aahrhus Sygehus
Aarhus, Denmark, 8000
France
Hospices Civils de Lyon
Bron Cedex, France, 69677
Germany
Charite - Universitätsmedizin Berlin
Berlin, Germany, 10117
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246
Spain
Institut d'Investigacio Biomedica de Girona Doctor Josep Trueta
Girona, Spain, 17007
United Kingdom
University of Glasgow
Glasgow, United Kingdom, G12 8QQ
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Investigators
Study Chair: Christian Gerloff, MD Universitätsklinikum Hamburg-Eppendorf
Principal Investigator: Goetz Thomalla, MD Universitätsklinikum Hamburg-Eppendorf
  More Information

Responsible Party: Götz Thomalla, MD, Coordinating Investigator, Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT01525290     History of Changes
Other Study ID Numbers: WAKE-UP
First Submitted: January 30, 2012
First Posted: February 2, 2012
Last Update Posted: July 19, 2017
Last Verified: July 2017

Keywords provided by Götz Thomalla, MD, Universitätsklinikum Hamburg-Eppendorf:
wake-up stroke
thrombolysis
magnetic resonance imaging (MRI)
diffusion weighted imaging (DWI)
fluid attenuated inversion recovery (FLAIR)

Additional relevant MeSH terms:
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Tissue Plasminogen Activator
Plasminogen
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action