Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)

Study Overview
=================
Brief Summary
-----------------
To determine whether the extent of the ischemic penumbra apparent on perfusion-diffusion MRI can be used to identify patients who would respond positively and safely to tissue plasminogen activator (tPA) beyond 3 hours post-stroke.

Official Title
-----------------
Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) in Acute Stroke

Conditions
-----------------
Stroke

Intervention / Treatment
-----------------
* Drug: Alteplase t-PA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who present: with acute hemispheric stroke within 3-6 hours of onset, have at least moderate limb weakness, a National Institute of Health Stroke Scale (NIHSS) score > 4, had a pre-stroke modified Rankin Scale (MRS) score of 0 - 2 and who are able to undergo CT and MRI, are eligible for this study. Exclusion Criteria: Females who are pregnant or breast-feeding, persons who have CT-verified hemorrhagic stroke, major ischemia ( > 33% of the middle cerebral artery (MCA) territory infarcted), subarachnoid hemorrhage, arteriovenous malformation, aneurysm, intracranial neoplasm that is terminal or poses a risk of hemorrhage , are comatose or severely obtunded with fixed eye deviation and complete hemiplegia, have had another stroke within the past 6 weeks, have had a seizure prior to the administration of the study drug, have active peptic ulceration, bleeding diatheses, previous intracerebral hemorrhage, blood pressure > 185/110, major surgery or trauma within the past 30 days, or any other contraindications to tPA have a presumed septic embolus or a myocardial infarction within the past 30 days blood glucose values are < 2.8 or > 22.0 mmol/L, pacemakers, aneurysm clips, implanted devices, claustrophobia, or any other contraindications to MRI, decreased consciousness, rapid clinical improvement, confounding neurological condition (e.g. dementia), any other life-threatening illness, or who are participating in another clinical trial, will be excluded from this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Alteplase t-PA|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Hypothesis - lesion growth |  |  | 
| In patients with penumbra, there will be attenuation of lesion growth (outcome T2 lesion volume - acute DWI volume ) with tPA. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Hypotheses |  |  | 
| In the non-penumbral group, lesion growth will be lower and will not be attenuated by tPA. |  |  | 
| Favourable functional outcome (mRS 0-2) will be more likely in patients with penumbra receiving tPA. |  |  | 
| That the proportion of patients achieving good neurological outcome (an 8 point improvement in NIH-SS or outcome NIH-SS of 0, 1) will be greater in those patients with a penumbra receiving tPA. |  |  | 
| Symptomatic hemorrhagic transformation (sICH) will be predicted by the size of the baseline DWI volume in those patients receiving tPA. |  |  | 
| Reperfusion (greater than 90% PWI lesion reduction, or recanalisation on MRA, between the acute and sub-acute interval), will be increased (in patients with penumbra) receiving tPA. |  |  | 
| In patients with malignant mismatch (Definition DWI 100ml or more and / or PWI 100ml or more) there will be unfavourable clinical outcome (even if there is attenuation of growth). |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MRI, Stroke, Thrombolysis, Echoplanar, Penumbra