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Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)

Primary Purpose

Stroke

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Alteplase t-PA
Sponsored by
Melbourne Health
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring Stroke, Thrombolysis, MRI, Echoplanar, Penumbra

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hunter New England Area Health Service
  • Royal Brisbane Hospital
  • Royal Adelaide Hospital
  • Flinders Medical Center
  • Royal Melbourne Hospital
  • St Vincents Hospital
  • Austin Hospital
  • Box Hill Hospital
  • Alfred Hospital
  • Royal Perth Hospital
  • Cliniques Universitaires St Luc
  • Auckland City Hospital
  • Christchurch Hospital
  • Southern General Hospital

Outcomes

Primary Outcome Measures

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

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).

Full Information

First Posted
October 11, 2005
Last Updated
May 28, 2013
Sponsor
Melbourne Health
Collaborators
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT00238537
Brief Title
Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)
Official Title
Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) in Acute Stroke
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Completed
Study Start Date
August 2001 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 2007 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Melbourne Health
Collaborators
Boehringer Ingelheim

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
Keywords
Stroke, Thrombolysis, MRI, Echoplanar, Penumbra

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
100 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Alteplase t-PA
Primary Outcome Measure Information:
Title
Primary Hypothesis - lesion growth
Title
In patients with penumbra, there will be attenuation of lesion growth (outcome T2 lesion volume - acute DWI volume ) with tPA.
Secondary Outcome Measure Information:
Title
Secondary Hypotheses
Title
In the non-penumbral group, lesion growth will be lower and will not be attenuated by tPA.
Title
Favourable functional outcome (mRS 0-2) will be more likely in patients with penumbra receiving tPA.
Title
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.
Title
Symptomatic hemorrhagic transformation (sICH) will be predicted by the size of the baseline DWI volume in those patients receiving tPA.
Title
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.
Title
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).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen M Davis, MD FRCP FRACP
Organizational Affiliation
Melbourne Health
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Geoffrey Donnan, MD FRACP
Organizational Affiliation
National Stroke Research Institute, Australia
Official's Role
Study Chair
Facility Information:
Facility Name
Hunter New England Area Health Service
City
Newcastle
State/Province
New South Wales
ZIP/Postal Code
2310
Country
Australia
Facility Name
Royal Brisbane Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4072
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Flinders Medical Center
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
St Vincents Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Austin Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3081
Country
Australia
Facility Name
Box Hill Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
Facility Name
Royal Perth Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6001
Country
Australia
Facility Name
Cliniques Universitaires St Luc
City
Brussels
ZIP/Postal Code
B-1200
Country
Belgium
Facility Name
Auckland City Hospital
City
Auckland
ZIP/Postal Code
92024
Country
New Zealand
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
4710
Country
New Zealand
Facility Name
Southern General Hospital
City
Glasgow
State/Province
Scotland
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23250996
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.
Results Reference
derived
PubMed Identifier
21474799
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.
Results Reference
derived
PubMed Identifier
18296121
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.
Results Reference
derived

Learn more about this trial

Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)

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