Clinical trial NCT00238537: Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)
Official title: Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) in Acute Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke
Keywords: Stroke
Thrombolysis
MRI
Echoplanar
Penumbra
Lead sponsor: Melbourne Health
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2005-10-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Primary Hypothesis - lesion growth
measure: In patients with penumbra, there will be attenuation of lesion growth (outcome T2 lesion volume - acute DWI volume ) with tPA.
Secondary outcomes:
measure: Secondary Hypotheses
measure: In the non-penumbral group, lesion growth will be lower and will not be attenuated by tPA.
measure: Favourable functional outcome (mRS 0-2) will be more likely in patients with penumbra receiving tPA.
measure: 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.
measure: Symptomatic hemorrhagic transformation (sICH) will be predicted by the size of the baseline DWI volume in those patients receiving tPA.
measure: 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.
measure: 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).
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: Hunter New England Area Health Service
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Adelaide
country: Australia
facility: Flinders Medical Center
state: South Australia
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Melbourne
country: Australia
facility: St Vincents Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Brussels
country: Belgium
facility: Cliniques Universitaires St Luc
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Glasgow
country: United Kingdom
facility: Southern General Hospital
state: Scotland
Study officials:
affiliation: Melbourne Health
name: Stephen M Davis, MD FRCP FRACP
role: STUDY_CHAIR
affiliation: National Stroke Research Institute, Australia
name: Geoffrey Donnan, MD FRACP
role: STUDY_CHAIR
References:
citation: Ogata T, Christensen S, Nagakane Y, Ma H, Campbell BC, Churilov L, Lansberg MG, Straka M, De Silva DA, Mlynash M, Bammer R, Olivot JM, Desmond PM, Albers GW, Davis SM, Donnan GA; EPITHET and DEFUSE Investigators. The effects of alteplase 3 to 6 hours after stroke in the EPITHET-DEFUSE combined dataset: post hoc case-control study. Stroke. 2013 Jan;44(1):87-93. doi: 10.1161/STROKEAHA.112.668301. Epub 2012 Dec 18.
citation: Mlynash M, Lansberg MG, De Silva DA, Lee J, Christensen S, Straka M, Campbell BC, Bammer R, Olivot JM, Desmond P, Donnan GA, Davis SM, Albers GW; DEFUSE-EPITHET Investigators. Refining the definition of the malignant profile: insights from the DEFUSE-EPITHET pooled data set. Stroke. 2011 May;42(5):1270-5. doi: 10.1161/STROKEAHA.110.601609. Epub 2011 Apr 7.
citation: Davis SM, Donnan GA, Parsons MW, Levi C, Butcher KS, Peeters A, Barber PA, Bladin C, De Silva DA, Byrnes G, Chalk JB, Fink JN, Kimber TE, Schultz D, Hand PJ, Frayne J, Hankey G, Muir K, Gerraty R, Tress BM, Desmond PM; EPITHET investigators. Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurol. 2008 Apr;7(4):299-309. doi: 10.1016/S1474-4422(08)70044-9. Epub 2008 Feb 28.