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

Phase 1

Conditions: Patients with acute ischemic stroke proven by MRI and unknown time from symptom onset which otherwise fulfil the approval criteria for intravenous thrombolysis in acute stroke
MedDRA version: 17.1Level: PTClassification code 10061256Term: Ischaemic strokeSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2011-005906-32-ES

Lead Sponsor: niversity Medical Center Hamburg-Eppendorf

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 503

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 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 clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective is to test efficacy and safety of MRI-based intravenous thrombolysis with Alteplase in patients waking up with stroke symptoms or patients with unknown symptom onset.;Secondary Objective: no secondary objectives;Primary end point(s): Primary Efficacy Endpoint<br>? ?Favourable outcome? defined by a score of 0-1 on the modified Rankin Scale (MRS) 90 (±10) days after stroke<br>Primary Safety Endpoints<br>?Mortality 90( ±)10 days after stroke<br>?Death or dependency 90 (±10) days after stroke (MRS 4-6);Timepoint(s) of evaluation of this end point: Primary Efficacy Endpoint<br>? 90 ±10 days after stroke<br>Primary Safety Endpoints<br>?90 ±10 days after stroke<br>?90 ±10 days after stroke

Secondary Outcome Measures

Name	Time	Method