Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)

Condition(s) targeted: Stroke

Intervention: Alteplase t-PA (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Melbourne Health

Official(s) and/or principal investigator(s):
Stephen M Davis, MD FRCP FRACP, Study Chair, Affiliation: Melbourne Health
Geoffrey Donnan, MD FRACP, Study Chair, Affiliation: National Stroke Research Institute, Australia

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

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

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:

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).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Cliniques Universitaires St Luc, Brussels B-1200, Belgium

Auckland City Hospital, Auckland 92024, New Zealand

Christchurch Hospital, Christchurch 4710, New Zealand

Hunter New England Area Health Service, Newcastle, New South Wales 2310, Australia

Royal Brisbane Hospital, Brisbane, Queensland 4072, Australia

Southern General Hospital, Glasgow, Scotland, United Kingdom

Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia

Flinders Medical Center, Adelaide, South Australia 5042, Australia

Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia

Austin Hospital, Melbourne, Victoria 3081, Australia

Box Hill Hospital, Melbourne, Victoria 3128, Australia

St Vincents Hospital, Melbourne, Victoria 3065, Australia

Alfred Hospital, Melbourne, Victoria 3144, Australia

Royal Perth Hospital, Perth, Western Australia 6001, Australia

Click here for more information about this study. Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)

Starting date: August 2001
Ending date: April 2007
Last updated: March 8, 2007