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

October 9, 2018 updated by: Götz Thomalla, MD, Universitätsklinikum Hamburg-Eppendorf

Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke: a Randomised, Double-blind, Placebo-controlled Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

501

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • Katholieke Universitet Leuven
  • Denmark
      • Aarhus, Denmark, 8000
        • Aarhus Universitetshospital, Aahrhus Sygehus
  • France
      • Bron Cedex, France, 69677
        • Hospices Civils de Lyon
  • Germany
      • Berlin, Germany, 10117
        • Charité - Universitätsmedizin Berlin
      • Hamburg, Germany, 20246
        • University Medical Center Hamburg-Eppendorf
  • Spain
      • Girona, Spain, 17007
        • Institut d'Investigacio Biomedica de Girona Doctor Josep Trueta
  • United Kingdom
      • Glasgow, United Kingdom, G12 8QQ
        • University of Glasgow

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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:
  • Activase
  • Actilyse
  • rt-PA
Placebo Comparator: Placebo
Intervention drug: placebo
Drug: Placebo
lyophilised powder to be reconstituted as solution indistinguishable from the active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy
Time Frame: 90 day after stroke
Favourable outcome (Modified Rankin Scale 0-1)
90 day after stroke
Safety
Time Frame: 90 day after stroke
  • Mortality
  • Death or dependency (Modified Rankin Scale 4-6)
90 day after stroke

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
90 days after stroke
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)
90 days after stroke

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitätsklinikum Hamburg-Eppendorf

Investigators

  • Study Chair: Christian Gerloff, MD, Universitatsklinikum Hamburg-Eppendorf
  • Principal Investigator: Goetz Thomalla, MD, Universitatsklinikum Hamburg-Eppendorf

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2012

Primary Completion (Actual)

October 1, 2018

Study Completion (Actual)

October 1, 2018

Study Registration Dates

First Submitted

January 30, 2012

First Submitted That Met QC Criteria

February 1, 2012

First Posted (Estimate)

February 2, 2012

Study Record Updates

Last Update Posted (Actual)

October 11, 2018

Last Update Submitted That Met QC Criteria

October 9, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WAKE-UP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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