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StrokePhase 3EXTENDNCT01580839

EXTEND (International): Extending the Time for Thrombolysis in Emergency Neurological Deficits (International)

A Phase 3 study testing Tissue Plasminogen Activator (Alteplase) in people with Stroke, run by Neuroscience Trials Australia at 1 site in Taiwan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary hypothesis being tested in this trial is that ischaemic stroke patients selected with significant penumbral mismatch (according to imaging criteria) at 4.5 (or 3 hours depending on local guidelines) - 9 hours post onset of stroke or after 'wake up stroke' (WUS) will have improved clinical outcomes when… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stroke
What is being tested?
Tissue Plasminogen Activator (Alteplase)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
45 participants
Where
1 siteTaiwan
Study dates
6 Dec 2012to 22 Aug 2018
Phase
Phase 3
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 presenting with hemispheric acute ischaemic stroke
  • Patient, family member or legally responsible person depending on local ethics requirements has given informed consent
  • Patient's age is ≥18 years (or as per local requirements)
  • Treatment onset can commence within 4.5 - 9 hours after stroke onset according to registered product information, or within 3 - 9 hours according to locally accepted guidelines.
  • Patients who wake with stroke may be included if neurological and other exclusion criteria are satisfied. These 'wake up' strokes are defined as having no symptoms at sleep onset, but stroke symptoms on waking. The time of stroke onset is to be taken as the mid-point between sleep onset (or last known to be normal) and time of waking. The maximum time window for randomisation is then 9 hours from the mid-point as described.
  • Significant neurological deficit (eg. NIHSS score of ≥ 4 - 26) with clinical signs of hemispheric infarction.
  • Penumbral mismatch - A "hypo-perfusion to core" volume ratio of greater than 1.2, and an absolute difference greater than 10ml (using a Magnetic Resonance (MR) or Computed Tomography (CT) Tmax > 6 second delay), between perfusion lesion and MR-DWI or Computed Tomography-Cerebral Blood Flow (CT-CBF) core lesion.
  • An infarct core lesion of less than or equal to 70ml using MR-DWI or CT-CBF

Who cannot join

  • Intracranial haemorrhage (ICH) identified by CT or MRI
  • Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in the patient having an NIHSS score of < 4 at randomization
  • Pre-stroke MRS score of ≥ 2 (indicating previous disability)
  • Contra indication to imaging with contrast agents
  • Infarct core >1/3 Middle Cerebral Artery (MCA) territory qualitatively
  • Participation in any investigational study in the previous 30 days
Show all 21Show fewer
  • Any terminal illness such that patient would not be expected to survive more than 1 year
  • Any condition that could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study (this applies to patients with severe microangiopathy such as haemolytic uremic syndrome or thrombotic thrombocytopenic purpura). The judgment is left to the discretion of the Investigator.
  • Pregnant women (clinically evident)
  • Previous stroke within last three months
  • Recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. At the discretion of each Investigator.
  • Current use of oral anticoagulants or a prolonged prothrombin time (INR > 1.7) if the patient is on warfarin
  • Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged activated thromboplastin time exceeding the upper limit of the local laboratory normal range.
  • Use of glycoprotein IIb - IIIa inhibitors within the past 72 hours. Use of single or dual agent oral platelet inhibitors (clopidogrel and/or low-dose aspirin) prior to study entry is permitted.
  • Clinically significant hypoglycaemia.
  • Uncontrolled hypertension defined by a blood pressure > 185 mmHg systolic or >110 mmHg diastolic on at least 2 separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure to within these limits. The definition of "aggressive treatment" is left to the discretion of the responsible Investigator.
  • Hereditary or acquired haemorrhagic diathesis
  • Gastrointestinal or urinary bleeding within the preceding 21 days
  • Major surgery within the preceding 14 days which poses risk in the opinion of the investigator.
  • Exposure to a thrombolytic agent within the previous 72 hours
  • Clinically deemed eligible for Endovascular Clot Retrieval (ECR) treatment by the treating team

Trial locations and contacts

1 site in 1 country.

Taiwan1 site

  • China Medical University Hospital

    Taichung, 40447

Other trials in Taiwan

About this study

Official title: Extending the Time for Thrombolysis in Emergency Neurological Deficits

The primary hypothesis being tested in this trial is that ischaemic stroke patients selected with significant penumbral mismatch (according to imaging criteria) at 4.5 (or 3 hours depending on local guidelines) - 9 hours post onset of stroke or after 'wake up stroke' (WUS) will have improved clinical outcomes when given intravenous tissue plasminogen activator (tPA) compared to placebo.

Conditions
Stroke
Being tested
Tissue Plasminogen Activator (Alteplase), Placebo
Keywords
ischemic stroke, ischemic penumbra, magnetic resonance imaging, MRI, diffusion imaging, DWI, perfusion imaging, PWI, thrombolysis, alteplase, tPA, EPITHET
Medical subject headings
Stroke, Ischemic Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tissue Plasminogen Activator (Alteplase)Drug

    Also called Actilyse, Activase, tPA, r-tPA

    0.9 mg/kg up to a maximum of 90mg, intravenous, 10% as bolus and the remainder over 1 hour

  • PlaceboDrug

    placebo provided as 50mg lyophilised powder to be reconstituted with sterile water in glass vials indistinguishable from active drug

Study groups in NCT01580839
Study groupRoleWhat they receive
intravenous tissue plasminogen activatorExperimentalNot described
Receives: Drug: Tissue Plasminogen Activator (Alteplase)
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Modified Rankin Scale (mRS) 0-1

    Measured: 3 months

Secondary outcomes (8)

  1. Categorical shift in modified Rankin Score (mRS)

    Measured: 3 months

  2. Change in ≥ 8 National Institutes of Health Stroke Scale (NIHSS) points or reaching ≤ 1 on this scale

    Measured: 3 months

  3. Death due to any cause

    Measured: 3 months

  4. Symptomatic Intracerebral Hemorrhage (ICH)

    Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS

    Measured: 24 hours

  5. Reperfusion

    Measured: 24 hours

  6. Recanalisation

    Measured: 24 hours

  7. Infarct growth

    Difference in volumetric Diffusion Weighted Image (DWI) volume between baseline and 24 hour Magnetic Resonance Imaging (MRI)

    Measured: 24 hours

  8. Recurrent stroke

    Measured: 3 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2012 (estimated)
  2. Study start6 Dec 2012
  3. Primary completion22 Aug 2018
  4. Study completion22 Aug 2018

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01580839
Sponsor's protocol ID
NTA0903
Acronym
EXTEND
Status last verified
Aug 2018
First submitted
17 Apr 2012
Last updated
31 Aug 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Bivard A, Churilov L, Ma H, Levi C, Campbell B, Yassi N, Meretoja A, Zhao H, Sharma G, Chen C, Davis S, Donnan G, Yan B, Parsons M; EXTEND investigators. Does variability in automated perfusion software outputs for acute ischemic stroke matter? Reanalysis of EXTEND perfusion imaging. CNS Neurosci Ther. 2022 Jan;28(1):139-144. doi: 10.1111/cns.13756. Epub 2021 Nov 16.

    PubMed 34786868

  • Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, Kleinig TJ, Wijeratne T, Curtze S, Dewey HM, Miteff F, Tsai CH, Lee JT, Phan TG, Mahant N, Sun MC, Krause M, Sturm J, Grimley R, Chen CH, Hu CJ, Wong AA, Field D, Sun Y, Barber PA, Sabet A, Jannes J, Jeng JS, Clissold B, Markus R, Lin CH, Lien LM, Bladin CF, Christensen S, Yassi N, Sharma G, Bivard A, Desmond PM, Yan B, Mitchell PJ, Thijs V, Carey L, Meretoja A, Davis SM, Donnan GA; EXTEND Investigators. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019 May 9;380(19):1795-1803. doi: 10.1056/NEJMoa1813046.

    PubMed 31067369

  • Churilov L, Ma H, Campbell BC, Davis SM, Donnan GA. Statistical Analysis Plan for EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial. Int J Stroke. 2020 Feb;15(2):231-238. doi: 10.1177/1747493018816101. Epub 2018 Dec 7.

    PubMed 30523735

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tissue Plasminogen Activator (Alteplase) in people with Stroke, run by Neuroscience Trials Australia at 1 site in Taiwan.

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 8 inclusion and 21 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 31 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Taiwan. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Modified Rankin Scale (mRS) 0-1 (time frame: 3 months). 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 NCT01580839, 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 31 Aug 2018.

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