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

This study is currently recruiting participants.
Verified April 2013 by National Stroke Research Institute, Australia
Sponsor:
Collaborators:
Commonwealth Scientific & Industry Research Organisation
Brain Research Institute
University of Melbourne
Melbourne Health
Information provided by (Responsible Party):
National Stroke Research Institute, Australia
ClinicalTrials.gov Identifier:
NCT00887328
First received: April 22, 2009
Last updated: April 30, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Stroke
Drug: Tissue Plasminogen Activator (Alteplase)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Extending the Time for Thrombolysis in Emergency Neurological Deficits

Resource links provided by NLM:


Further study details as provided by National Stroke Research Institute, Australia:

Primary Outcome Measures:
  • Modified Rankin Scale (mRS) 0-1 [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Categorical shift in modified Rankin Score (mRS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Change in ≥ 8 NIHSS points or reaching ≤ 1 on this scale [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Death due to any cause [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Symptomatic ICH [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS

  • Reperfusion [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Recanalisation [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Infarct growth [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Difference in volumetric DWI volume between baseline and 24 hour MRI

  • Recurrent stroke [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]
  • Depression (Montgomery-Asberg Depression Rating Scale [MADRS]) [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]
  • Quality of life (Stroke Impact Scale) [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: June 2010
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IV tPA
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients presenting with 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 imaging** -Using a Tmax > 6 second delay, a perfusion (PWI)lesion volume to diffusion (DWI) lesion volume ratio >1.2, a DWI volume ≤70mL and a PWI-DWI difference >10 ml.

    • 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 and a prolonged prothrombin time (INR > 1.6)
  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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00887328

Contacts
Contact: Sue Bates, BSc(Hons) +61 3 9035 7230 sbates@neurotrialsaustralia.com

Locations
Australia, New South Wales
Gosford Hospital Recruiting
Kanwal, New South Wales, Australia, 2259
Principal Investigator: Joh Sturm         
John Hunter Hospital Recruiting
Newcastle, New South Wales, Australia
Principal Investigator: Mark W Parsons, PhD FRACP         
Royal North Shore Hospital Not yet recruiting
St. Leonards, New South Wales, Australia, 2065
Principal Investigator: Martin Krause         
St. Vincent's Hospital Active, not recruiting
Sydney, New South Wales, Australia, 6009
Westmead Hospital Recruiting
Westmead, New South Wales, Australia, 2145
Principal Investigator: Neil Mahant         
Australia, Queensland
Royal Brisbane & Women's Hospital Recruiting
Brisbane, Queensland, Australia, 4029
Principal Investigator: Stephen Read         
Nambour General Hospital Recruiting
Nambour, Queensland, Australia, 4560
Principal Investigator: Rohan Grimley         
Australia, South Australia
Royal Adelaide Hospital Active, not recruiting
Adelaide, South Australia, Australia, 5000
Flinders Medical Centre Not yet recruiting
Bedford Park, South Australia, Australia, 5042
Principal Investigator: Andrew Lee         
Australia, Victoria
Box Hill Hospital Recruiting
Box Hill, Victoria, Australia, 3128
Principal Investigator: Christopher Bladin         
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
Principal Investigator: Thanh Phan         
Western Hospital Recruiting
Footscray, Victoria, Australia, 3011
Principal Investigator: Tissa Wijeratne         
Austin Hospital Recruiting
Heidelberg, Victoria, Australia
Principal Investigator: Helen Dewey         
Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia, 3050
Principal Investigator: Stephen M Davis, MD FRACP         
Epworth Healthcare Active, not recruiting
Richmond, Victoria, Australia, 3121
Australia, Western Australia
Sir Charles Gairdner Hospital Not yet recruiting
Nedlands, Western Australia, Australia, 6009
Principal Investigator: David Blacker         
Royal Perth Hospital Not yet recruiting
Perth, Western Australia, Australia, 6000
Principal Investigator: Graeme Hankey         
New Zealand
Auckland Hospital Recruiting
Auckland, New Zealand, 1001
Principal Investigator: Alan Barber         
Sponsors and Collaborators
National Stroke Research Institute, Australia
Commonwealth Scientific & Industry Research Organisation
Brain Research Institute
University of Melbourne
Melbourne Health
Investigators
Principal Investigator: Geoffrey Donnan, MD FRACP National Stroke Research Institute, Australia
Principal Investigator: Stephen Davis, MD FRACP University of Melbourne
  More Information

Additional Information:
No publications provided

Responsible Party: National Stroke Research Institute, Australia
ClinicalTrials.gov Identifier: NCT00887328     History of Changes
Other Study ID Numbers: NTA0901
Study First Received: April 22, 2009
Last Updated: April 30, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by National Stroke Research Institute, Australia:
ischemic stroke
ischemic penumbra
magnetic resonance imaging
MRI
diffusion imaging
DWI
perfusion imaging
PWI
thrombolysis
alteplase
tPA
EPITHET

Additional relevant MeSH terms:
Emergencies
Stroke
Disease Attributes
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on April 17, 2014