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Extending the Time for Thrombolysis in Emergency Neurological Deficits (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.
 
ClinicalTrials.gov Identifier: NCT00887328
Recruitment Status : Completed
First Posted : April 23, 2009
Last Update Posted : August 31, 2018
Sponsor:
Collaborators:
Commonwealth Scientific and Industrial Research Organisation, Australia
University of Melbourne
Melbourne Health
The Florey Institute of Neuroscience and Mental Health
Information provided by (Responsible Party):
Neuroscience Trials Australia

Tracking Information
First Submitted Date  ICMJE April 22, 2009
First Posted Date  ICMJE April 23, 2009
Last Update Posted Date August 31, 2018
Study Start Date  ICMJE June 2010
Actual Primary Completion Date August 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2010)
Modified Rankin Scale (mRS) 0-1 [ Time Frame: 3 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 22, 2009)
Modified Rankin Scale [ Time Frame: 3 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2010)
  • Categorical shift in modified Rankin Score (mRS) [ Time Frame: 3 months ]
  • Change in ≥ 8 NIHSS points or reaching ≤ 1 on this scale [ Time Frame: 3 months ]
  • Death due to any cause [ Time Frame: 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
  • Reperfusion [ Time Frame: 24 hours ]
  • Recanalisation [ Time Frame: 24 hours ]
  • Infarct growth [ Time Frame: 24 hours ]
    Difference in volumetric DWI volume between baseline and 24 hour MRI
  • Recurrent stroke [ Time Frame: 3 and 12 months ]
  • Depression (Montgomery-Asberg Depression Rating Scale [MADRS]) [ Time Frame: 3 and 12 months ]
  • Quality of life (Stroke Impact Scale) [ Time Frame: 3 and 12 months ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Extending the Time for Thrombolysis in Emergency Neurological Deficits
Official Title  ICMJE Extending the Time for Thrombolysis in Emergency Neurological Deficits
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Stroke
Intervention  ICMJE
  • 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
  • Drug: Placebo
    placebo provided as 50mg lyophilised powder to be reconstituted with sterile water in glass vials indistinguishable from active drug
Study Arms  ICMJE
  • Experimental: IV tPA
    intravenous tissue plasminogen activator
    Intervention: Drug: Tissue Plasminogen Activator (Alteplase)
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 30, 2018)
180
Original Estimated Enrollment  ICMJE
 (submitted: April 22, 2009)
400
Actual Study Completion Date  ICMJE August 27, 2018
Actual Primary Completion Date August 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Finland,   New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00887328
Other Study ID Numbers  ICMJE NTA0901
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Neuroscience Trials Australia
Study Sponsor  ICMJE Neuroscience Trials Australia
Collaborators  ICMJE
  • Commonwealth Scientific and Industrial Research Organisation, Australia
  • University of Melbourne
  • Melbourne Health
  • The Florey Institute of Neuroscience and Mental Health
Investigators  ICMJE
Principal Investigator: Geoffrey Donnan, MD FRACP The Florey Institute of Neuroscence and Mental Health
Principal Investigator: Stephen Davis, MD FRACP University of Melbourne
PRS Account Neuroscience Trials Australia
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP