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

Sponsor
Universitätsklinikum Hamburg-Eppendorf (Other)
Overall Status
Completed
CT.gov ID
NCT01525290
Collaborator
(none)
501
Enrollment
7
Locations
2
Arms
73
Actual Duration (Months)
71.6
Patients Per Site
1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
501 participants
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
Actual Study Start Date :
Sep 1, 2012
Actual Primary Completion Date :
Oct 1, 2018
Actual Study Completion Date :
Oct 1, 2018

Arms and Interventions

Arm Intervention/Treatment
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

    Outcome Measures

    Primary Outcome Measures

    1. Efficacy [90 day after stroke]

      Favourable outcome (Modified Rankin Scale 0-1)

    2. Safety [90 day after stroke]

      Mortality Death or dependency (Modified Rankin Scale 4-6)

    Secondary Outcome Measures

    1. Efficacy [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

    2. Safety [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)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Katholieke Universitet Leuven Leuven Belgium 3000
    2 Aarhus Universitetshospital, Aahrhus Sygehus Aarhus Denmark 8000
    3 Hospices Civils de Lyon Bron Cedex France 69677
    4 Charite - Universitätsmedizin Berlin Berlin Germany 10117
    5 University Medical Center Hamburg-Eppendorf Hamburg Germany 20246
    6 Institut d'Investigacio Biomedica de Girona Doctor Josep Trueta Girona Spain 17007
    7 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Götz Thomalla, MD, Coordinating Investigator, Universitätsklinikum Hamburg-Eppendorf
    ClinicalTrials.gov Identifier:
    NCT01525290
    Other Study ID Numbers:
    • WAKE-UP
    First Posted:
    Feb 2, 2012
    Last Update Posted:
    Oct 11, 2018
    Last Verified:
    Oct 1, 2018
    Keywords provided by Götz Thomalla, MD, Coordinating Investigator, 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
    Ischemic Stroke
    Tissue Plasminogen Activator

    Study Results

    No Results Posted as of Oct 11, 2018