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

August 30, 2018 updated by: Neuroscience Trials Australia
The primary hypothesis being tested in this trial is that ischaemic stroke patients selected with significant penumbral mismatch (measured by MRI criteria) at 3 - 9 hours post onset of stroke will have improved clinical outcomes when given intravenous tissue plasminogen activator (tPA) compared to placebo.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

180

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Kanwal, New South Wales, Australia, 2259
        • Gosford Hospital
      • Newcastle, New South Wales, Australia
        • John Hunter Hospital
      • St. Leonards, New South Wales, Australia, 2065
        • Royal North Shore Hospital
      • Sydney, New South Wales, Australia, 6009
        • St. Vincent's Hospital
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • Queensland
      • Brisbane, Queensland, Australia, 4029
        • Royal Brisbane & Women's Hospital
      • Gold Coast, Queensland, Australia
        • Gold Coast University Hospital
      • Nambour, Queensland, Australia, 4560
        • Sunshine Coast University Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
      • Elizabeth Vale, South Australia, Australia, 5112
        • Lyell McEwin Hospital
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Box Hill Hospital
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre
      • Footscray, Victoria, Australia, 3011
        • Western Hospital
      • Geelong, Victoria, Australia, 3220
        • Geelong Hospital
      • Heidelberg, Victoria, Australia
        • Austin Hospital
      • Melbourne, Victoria, Australia, 3050
        • Royal Melbourne Hospital
      • Richmond, Victoria, Australia, 3121
        • Epworth Healthcare
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
      • Perth, Western Australia, Australia, 6000
        • Royal Perth Hospital
      • Helsinki, Finland
        • Helsinki University Central Hospital
      • Auckland, New Zealand, 1001
        • Auckland Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients presenting with hemispheric acute ischaemic stroke
  2. Patient, family member or legally responsible person depending on local ethics requirements has given informed consent
  3. Patient's age is ≥18 years
  4. Treatment onset can commence within ≥ 3 - 9 hours after stroke onset according to registered product information, or within 4.5 - 9 hours according to locally accepted guidelines*.

    (*Guidelines are currently under international review - advisory statement issued by the Stroke Council, American Heart Association and American Stroke Association)

  5. 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.
  6. NIHSS score of ≥ 4 - 26 with clinical signs of hemispheric infarction.
  7. Penumbral mismatch - A "hypo-perfusion to core" volume ratio of greater than 1.2 and an absolute difference greater than 10mL (using a MR or CT Tmax > 6 second delay) between perfusion lesion and MR-DWI or CT-CBF core lesion.
  8. An ischaemic core lesion volume of less than or equal to 70 ml using MR-DWI or CT-CBF ** Patients may be consented before or after penumbral screening depending upon local practice. The entire cohort of patients consented onto the study will be followed up with clinical assessments and biomarker studies regardless of eligibility for randomisation to treatment based on penumbral mismatch criteria

Exclusion Criteria:

  1. Intracranial haemorrhage (ICH) identified by CT or MRI
  2. 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
  3. Pre-stroke MRS score of ≥ 2 (indicating previous disability)
  4. Contra indication to imaging with MR with contrast agents
  5. Infarct core >1/3 MCA territory qualitatively
  6. Participation in any investigational study in the previous 30 days
  7. Any terminal illness such that patient would not be expected to survive more than 1 year
  8. 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.
  9. Pregnant women (clinically evident)
  10. Previous stroke within last three months
  11. 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.
  12. Current use of oral anticoagulants or a prolonged prothrombin time (INR > 1.7) if the patient is on warfarin
  13. Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and an activated prolonged partial thromboplastin time exceeding the upper limit of the local laboratory normal range.
  14. 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.
  15. Clinically significant hypoglycaemia.
  16. 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.
  17. Hereditary or acquired haemorrhagic diathesis
  18. Gastrointestinal or urinary bleeding within the preceding 21 days
  19. Major surgery within the preceding 14 days which poses risk in the opinion of the investigator.
  20. Exposure to a thrombolytic agent within the previous 72 hours
  21. Clinically deemed eligible for Endovascular Clot Retrieval (ECR) treatment by the treating team

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
placebo provided as 50mg lyophilised powder to be reconstituted with sterile water in glass vials indistinguishable from active drug
Experimental: IV tPA
intravenous tissue plasminogen activator
0.9 mg/kg up to a maximum of 90mg, intravenous, 10% as bolus and the remainder over 1 hour
Other Names:
  • tPA
  • Activase
  • Actilyse
  • r-tPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Modified Rankin Scale (mRS) 0-1
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Categorical shift in modified Rankin Score (mRS)
Time Frame: 3 months
3 months
Death due to any cause
Time Frame: 3 months
3 months
Reperfusion
Time Frame: 24 hours
24 hours
Recanalisation
Time Frame: 24 hours
24 hours
Recurrent stroke
Time Frame: 3 and 12 months
3 and 12 months
Change in ≥ 8 NIHSS points or reaching ≤ 1 on this scale
Time Frame: 3 months
3 months
Symptomatic ICH
Time Frame: 24 hours
Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS
24 hours
Infarct growth
Time Frame: 24 hours
Difference in volumetric DWI volume between baseline and 24 hour MRI
24 hours
Depression (Montgomery-Asberg Depression Rating Scale [MADRS])
Time Frame: 3 and 12 months
3 and 12 months
Quality of life (Stroke Impact Scale)
Time Frame: 3 and 12 months
3 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Stephen Davis, MD FRACP, University of Melbourne
  • Principal Investigator: Geoffrey Donnan, MD FRACP, The Florey Institute of Neuroscence and Mental Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

August 27, 2018

Study Completion (Actual)

August 27, 2018

Study Registration Dates

First Submitted

April 22, 2009

First Submitted That Met QC Criteria

April 22, 2009

First Posted (Estimate)

April 23, 2009

Study Record Updates

Last Update Posted (Actual)

August 31, 2018

Last Update Submitted That Met QC Criteria

August 30, 2018

Last Verified

August 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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