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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00238537




Registration number
NCT00238537
Ethics application status
Date submitted
11/10/2005
Date registered
13/10/2005
Date last updated
30/05/2013

Titles & IDs
Public title
Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)
Scientific title
Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) in Acute Stroke
Secondary ID [1] 0 0
TGA Trial Number: 1999/271
Secondary ID [2] 0 0
145671
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Hypothesis - lesion growth
Timepoint [1] 0 0
Primary outcome [2] 0 0
In patients with penumbra, there will be attenuation of lesion growth (outcome T2 lesion volume - acute DWI volume ) with tPA.
Timepoint [2] 0 0
Secondary outcome [1] 0 0
Secondary Hypotheses
Timepoint [1] 0 0
Secondary outcome [2] 0 0
In the non-penumbral group, lesion growth will be lower and will not be attenuated by tPA.
Timepoint [2] 0 0
Secondary outcome [3] 0 0
Favourable functional outcome (mRS 0-2) will be more likely in patients with penumbra receiving tPA.
Timepoint [3] 0 0
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Secondary outcome [5] 0 0
Symptomatic hemorrhagic transformation (sICH) will be predicted by the size of the baseline DWI volume in those patients receiving tPA.
Timepoint [5] 0 0
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Secondary outcome [7] 0 0
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).
Timepoint [7] 0 0

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2001
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Hunter New England Area Health Service - Newcastle
Recruitment hospital [2] 0 0
Royal Brisbane Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Flinders Medical Center - Adelaide
Recruitment hospital [5] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [6] 0 0
St Vincents Hospital - Melbourne
Recruitment hospital [7] 0 0
Austin Hospital - Melbourne
Recruitment hospital [8] 0 0
Box Hill Hospital - Melbourne
Recruitment hospital [9] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [10] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Newcastle
Recruitment postcode(s) [2] 0 0
4072 - Brisbane
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5042 - Adelaide
Recruitment postcode(s) [5] 0 0
3050 - Melbourne
Recruitment postcode(s) [6] 0 0
3065 - Melbourne
Recruitment postcode(s) [7] 0 0
3081 - Melbourne
Recruitment postcode(s) [8] 0 0
3128 - Melbourne
Recruitment postcode(s) [9] 0 0
3144 - Melbourne
Recruitment postcode(s) [10] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
New Zealand
State/province [2] 0 0
Auckland
Country [3] 0 0
New Zealand
State/province [3] 0 0
Christchurch
Country [4] 0 0
United Kingdom
State/province [4] 0 0
Scotland

Funding & Sponsors
Primary sponsor type
Other
Name
Melbourne Health
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Boehringer Ingelheim
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00238537
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Stephen M Davis, MD FRCP FRACP
Address 0 0
Melbourne Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00238537