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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01580839
Recruitment Status : Completed
First Posted : April 19, 2012
Last Update Posted : August 31, 2018
China Medical University Hospital
Information provided by (Responsible Party):
Neuroscience Trials Australia

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.

Condition or disease Intervention/treatment Phase
Stroke Drug: Tissue Plasminogen Activator (Alteplase) Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Extending the Time for Thrombolysis in Emergency Neurological Deficits
Actual Study Start Date : December 6, 2012
Actual Primary Completion Date : August 22, 2018
Actual Study Completion Date : August 22, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: intravenous tissue plasminogen activator Drug: Tissue Plasminogen Activator (Alteplase)
0.9 mg/kg up to a maximum of 90mg, intravenous, 10% as bolus and the remainder over 1 hour
Other Names:
  • Actilyse
  • Activase
  • tPA
  • r-tPA

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

Primary Outcome Measures :
  1. Modified Rankin Scale (mRS) 0-1 [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Categorical shift in modified Rankin Score (mRS) [ Time Frame: 3 months ]
  2. Change in ≥ 8 National Institutes of Health Stroke Scale (NIHSS) points or reaching ≤ 1 on this scale [ Time Frame: 3 months ]
  3. Death due to any cause [ Time Frame: 3 months ]
  4. Symptomatic Intracerebral Hemorrhage (ICH) [ Time Frame: 24 hours ]
    Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS

  5. Reperfusion [ Time Frame: 24 hours ]
  6. Recanalisation [ Time Frame: 24 hours ]
  7. Infarct growth [ Time Frame: 24 hours ]
    Difference in volumetric Diffusion Weighted Image (DWI) volume between baseline and 24 hour Magnetic Resonance Imaging (MRI)

  8. Recurrent stroke [ Time Frame: 3 and 12 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01580839

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China Medical University Hospital
Taichung, Taiwan, 40447
Sponsors and Collaborators
Neuroscience Trials Australia
China Medical University Hospital
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Principal Investigator: Geoffrey Donnan, MD FRACP The Florey Institute of Neuroscience and Mental Health
Principal Investigator: Stephen Davis, MD FRACP University of Melbourne
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Neuroscience Trials Australia Identifier: NCT01580839    
Other Study ID Numbers: NTA0903
First Posted: April 19, 2012    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018
Keywords provided by Neuroscience Trials Australia:
ischemic stroke
ischemic penumbra
magnetic resonance imaging
diffusion imaging
perfusion imaging
Additional relevant MeSH terms:
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Disease Attributes
Pathologic Processes
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action