acute ischemische beroerte cerebrovascular accident stroke
Conditions
Interventions
In this trial we will use modern multiparametric MRI techniques applying a new
diagnostic algorithm to identify patients likely to benefit from treatment. We
will enroll 800 patients iof which 400 w
Sponsors
University Medical Center Hamburg-Eppendorf
Eligibility
Age
18 Years to 99 Years
Inclusion 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 and 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
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 inidicative 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Efficacy endpoint : - "Favourable Outcome" defined by a score of 0-1 on the Modified Ranking Scale (MRS) 90 (+/-10) days after stroke Primary Safety Endpoints : - Mortality 90 (+/-10) days after stroke - Death or dependency 90 (+/-10) days after stroke (MRS 4-6) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary efficacy endpoints : - Global Outcome Score (combination of MRS0-1, NIHSS 0-1, Barthel Index 95-100, Glasgow Coma Scale 1) 90 (+/-10) days after stroke - Categorical shift in MRS 90 (+/-10) days after stroke - Responder analysis relating MRS 90 (+/-10) days after stroke to baseline NIHSS score : "response" defined by NIHSS14 = MRS 0-2 - Infarct volume after 22-36 hours - Depressive symptoms 90 (+/-10) dyays after stroke (Beck Depression Inventory) - Functional Health Status and Quality of Life 90 (+/-10) days after stroke (EQ-5D) - Use of health care system resources 90 (+/-10) days after stroke) Secondary Safety endpoints : - Symptomatic intracranial haemorrhage (SICH) as defined in SITS-MOST - SICH as defined in ECASS II - SICH as defined in NINDS - Parenchymal haemorrhage type 2 (PH-2) - 22-36 hours after treatment | — |
Countries
Netherlands
Outcome results
None listed