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

Active, not recruiting

Phase 3 Results N/A

Update History

21 Jul '17
The eligibility criteria were updated.
New
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
Old
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
A location was updated in Leuven.
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The overall status was removed for Katholieke Universitet Leuven.
A location was updated in Aarhus.
New
The overall status was removed for Aarhus Universitetshospital, Aahrhus Sygehus.
A location was updated in Bron Cedex.
New
The overall status was removed for Hospices Civils de Lyon.
A location was updated in Berlin.
New
The overall status was removed for Charite - Universitätsmedizin Berlin.
A location was updated in Hamburg.
New
The overall status was removed for University Medical Center Hamburg-Eppendorf.
A location was updated in Girona.
New
The overall status was removed for Institut d'Investigacio Biomedica de Girona Doctor Josep Trueta.
A location was updated in Glasgow.
New
The overall status was removed for University of Glasgow.
24 May '17
The gender criteria for eligibility was updated to "All."
12 Sep '14
A location was updated in Aarhus.
New
The overall status was removed for Aarhus Universitetshospital, Aahrhus Sygehus.
A location was updated in Bron Cedex.
New
The overall status was removed for Hospices Civils de Lyon.
A location was updated in Girona.
New
The overall status was removed for Institut d'Investigacio Biomedica de Girona Doctor Josep Trueta.
A location was updated in Glasgow.
New
The overall status was removed for University of Glasgow.
6 Nov '12
A location was updated in Leuven.
New
The overall status was removed for Katholieke Universitet Leuven.
A location was updated in Berlin.
New
The overall status was removed for Charite - Universitätsmedizin Berlin.
A location was updated in Hamburg.
New
The overall status was removed for University Medical Center Hamburg-Eppendorf.