Efficacy and safety of MRI-based thrombolysis in wake-up stroke: a randomised, double-blind, placebo-controlled trial

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 100

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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Efficacy endpoint :<br /><br><br /><br>- Favourable Outcome defined by a score of 0-1 on the Modified Ranking Scale<br /><br>(MRS) 90 (+/-10) days after stroke<br /><br><br /><br>Primary Safety Endpoints :<br /><br><br /><br>- Mortality 90 (+/-10) days after stroke<br /><br><br /><br>- Death or dependency 90 (+/-10) days after stroke (MRS 4-6)</p><br>

Secondary Outcome Measures