Efficacy and safety of MRI-based thrombolysis in wake-upstroke

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 800

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

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 effective use of anticoagulants (e.g. Phenprocoumon, Warfarin, or new direct oral anticoagulants such as Apixaban, Dabigatran or Rivaroxaban) or current use of heparin and elevated thromboplastin time (low-dose subcutaneous heparin is allowed); inclusion may be considered in patients using vitamin K-antagonists (Phenprocoumon or Warfarin) when appropriate tests of anticoagulant activity (INR) show no clinically relevant activity
- 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