StrokePhase 2NCT00238537
Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET)
A Phase 2 study testing Alteplase t-PA in people with Stroke, run by Melbourne Health at 14 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Alteplase t-PA
- How many people
- 100 participants
- Where
- 14 sitesin 4 countries
- Study dates
- Aug 2001to Apr 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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,
Show all 15Show fewer
- 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.
Trial locations and contacts
14 sites in 4 countries.
14 sites in 4 countries
Australia10 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Flinders Medical Center
Adelaide, South Australia, 5042
Royal Brisbane Hospital
Brisbane, Queensland, 4072
Royal Melbourne Hospital
Melbourne, Victoria, 3050
St Vincents Hospital
Melbourne, Victoria, 3065
Austin Hospital
Melbourne, Victoria, 3081
Box Hill Hospital
Melbourne, Victoria, 3128
Alfred Hospital
Melbourne, Victoria, 3144
Hunter New England Area Health Service
Newcastle, New South Wales, 2310
Royal Perth Hospital
Perth, Western Australia, 6001
New Zealand2 sites
Auckland City Hospital
Auckland, 92024
Christchurch Hospital
Christchurch, 4710
About this study
Official title: Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) in Acute Stroke
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.
- Conditions
- Stroke
- Being tested
- Alteplase t-PA
- Keywords
- Stroke, Thrombolysis, MRI, Echoplanar, Penumbra
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alteplase t-PADrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (7)
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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2005 (estimated)
- Study startAug 2001
- Study completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 100 participants
Sponsor and investigators
- Lead sponsor
- Melbourne Health
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Investigators
- Stephen M Davis, MD FRCP FRACP, Study chair, Melbourne HealthGeoffrey Donnan, MD FRACP, Study chair, National Stroke Research Institute, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00238537
- Sponsor's protocol ID
- 145671
- Other IDs
- TGA Trial Number: 1999/271, Enterprise ID: 15314
- Status last verified
- May 2009
- First submitted
- 11 Oct 2005
- Last updated
- 30 May 2013
- Results posted
- No
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.
PubMed 23250996Mlynash 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.
PubMed 21474799Davis 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.
PubMed 18296121
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) in Acute Stroke
- ClinicalTrials.gov ID
- NCT00238537
- Acronym / sponsor ID
- 145671
- Conditions
- Stroke
- Keywords
- Stroke, Thrombolysis, MRI, Echoplanar, Penumbra
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants
- Lead sponsor
- Melbourne HealthUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- Aug 2001
- Study completion
- Apr 2007
- First posted
- 13 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alteplase t-PA | Drug | – |
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.
7 secondary outcomes
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2013.
- Derived from this study: PubMed 23250996Ogata 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.
- Derived from this study: PubMed 21474799Mlynash 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.
- Derived from this study: PubMed 18296121Davis 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen M Davis, MD FRCP FRACP study chair
Melbourne Health
Geoffrey Donnan, MD FRACP study chair
National Stroke Research Institute, Australia
14 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alteplase t-PA in people with Stroke, run by Melbourne Health at 14 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Australia, New Zealand, Belgium, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Hypothesis - lesion growth. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00238537, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2013.