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

NCT ID: NCT01525290

Last Updated: 2018-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 501 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2018-10-31

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.

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.

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

intravenous tissue plasminogen activator

Intervention drug: intravenous tissue plasminogen activator (tPA), alteplase

Group Type: EXPERIMENTAL

Alteplase

Intervention Type: DRUG

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

Placebo

Intervention drug: placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

lyophilised powder to be reconstituted as solution indistinguishable from the active drug

Interventions

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

Intervention Type: DRUG

Placebo

lyophilised powder to be reconstituted as solution indistinguishable from the active drug

Intervention Type: DRUG

Other Intervention Names

Actilyse; Activase; rt-PA

Eligibility Criteria

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

• 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

• 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)

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role: lead

Responsible Party

Götz Thomalla, MD

Coordinating Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christian Gerloff, MD

Role: STUDY_CHAIR

Universitätsklinikum Hamburg-Eppendorf

Goetz Thomalla, MD

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinikum Hamburg-Eppendorf

Locations

Katholieke Universitet Leuven

Leuven, , Belgium

Aarhus Universitetshospital, Aahrhus Sygehus

Aarhus, , Denmark

Hospices Civils de Lyon

Bron, , France

Charite - Universitätsmedizin Berlin

Berlin, , Germany

University Medical Center Hamburg-Eppendorf

Hamburg, , Germany

Institut d'Investigacio Biomedica de Girona Doctor Josep Trueta

Girona, , Spain

University of Glasgow

Glasgow, , United Kingdom

Countries

Belgium; Denmark; France; Germany; Spain; United Kingdom

References

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Other Identifiers

WAKE-UP

Identifier Type: -

Identifier Source: org_study_id