NCT01580839

Brief 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 given intravenous tissue plasminogen activator (tPA) compared to placebo.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at below P25 for phase_3 stroke

Timeline
Completed

Started Dec 2012

Longer than P75 for phase_3 stroke

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 17, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 19, 2012

Completed
8 months until next milestone

Study Start

First participant enrolled

December 6, 2012

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 22, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 22, 2018

Completed
Last Updated

August 31, 2018

Status Verified

August 1, 2018

Enrollment Period

5.7 years

First QC Date

April 17, 2012

Last Update Submit

August 30, 2018

Conditions

Stroke

Keywords

ischemic strokeischemic penumbramagnetic resonance imagingMRIdiffusion imagingDWIperfusion imagingPWIthrombolysisalteplasetPAEPITHET

Outcome Measures

Primary Outcomes (1)

  • Modified Rankin Scale (mRS) 0-1

    3 months

Secondary Outcomes (8)

  • Categorical shift in modified Rankin Score (mRS)

    3 months

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

    3 months

  • Death due to any cause

    3 months

  • Symptomatic Intracerebral Hemorrhage (ICH)

    24 hours

  • Reperfusion

    24 hours

  • +3 more secondary outcomes

Study Arms (2)

intravenous tissue plasminogen activator

EXPERIMENTAL
Drug: Tissue Plasminogen Activator (Alteplase)

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

Tissue Plasminogen Activator (Alteplase)DRUG

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

Also known as: Actilyse, Activase, tPA, r-tPA
intravenous tissue plasminogen activator
PlaceboDRUG

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

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • 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
  • 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
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Related Publications (3)

  • 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.

    PMID: 34786868DERIVED

  • 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.

    PMID: 31067369DERIVED

  • 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.

    PMID: 30523735DERIVED

MeSH Terms

Conditions

StrokeIschemic Stroke

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine EndopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesSerine ProteasesPlasminogen ActivatorsBlood Coagulation FactorsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsBiological Factors

Study Officials

  • Geoffrey Donnan, MD FRACP

    The Florey Institute of Neuroscience and Mental Health

    PRINCIPAL INVESTIGATOR

  • Stephen Davis, MD FRACP

    University of Melbourne

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 17, 2012

First Posted

April 19, 2012

Study Start

December 6, 2012

Primary Completion

August 22, 2018

Study Completion

August 22, 2018

Last Updated

August 31, 2018

Record last verified: 2018-08

Locations

TW(1)