- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00887328
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
Intervention / Treatment
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
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New South Wales
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Kanwal, New South Wales, Australia, 2259
- Gosford Hospital
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Newcastle, New South Wales, Australia
- John Hunter Hospital
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St. Leonards, New South Wales, Australia, 2065
- Royal North Shore Hospital
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Sydney, New South Wales, Australia, 6009
- St. Vincent's Hospital
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Westmead, New South Wales, Australia, 2145
- Westmead Hospital
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Queensland
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Brisbane, Queensland, Australia, 4029
- Royal Brisbane & Women's Hospital
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Gold Coast, Queensland, Australia
- Gold Coast University Hospital
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Nambour, Queensland, Australia, 4560
- Sunshine Coast University Hospital
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South Australia
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Adelaide, South Australia, Australia, 5000
- Royal Adelaide Hospital
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Bedford Park, South Australia, Australia, 5042
- Flinders Medical Centre
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Elizabeth Vale, South Australia, Australia, 5112
- Lyell McEwin Hospital
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Victoria
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Box Hill, Victoria, Australia, 3128
- Box Hill Hospital
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Clayton, Victoria, Australia, 3168
- Monash Medical Centre
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Footscray, Victoria, Australia, 3011
- Western Hospital
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Geelong, Victoria, Australia, 3220
- Geelong Hospital
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Heidelberg, Victoria, Australia
- Austin Hospital
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Melbourne, Victoria, Australia, 3050
- Royal Melbourne Hospital
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Richmond, Victoria, Australia, 3121
- Epworth Healthcare
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Sir Charles Gairdner Hospital
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Perth, Western Australia, Australia, 6000
- Royal Perth Hospital
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Helsinki, Finland
- Helsinki University Central Hospital
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Auckland, New Zealand, 1001
- Auckland Hospital
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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:
- 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
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)
- 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.
- 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 MR or CT Tmax > 6 second delay) between perfusion lesion and MR-DWI or CT-CBF core lesion.
- 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:
- 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 MR with contrast agents
- Infarct core >1/3 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 an activated prolonged partial 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
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
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placebo provided as 50mg lyophilised powder to be reconstituted with sterile water in glass vials indistinguishable from active drug
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Experimental: IV tPA
intravenous tissue plasminogen activator
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0.9 mg/kg up to a maximum of 90mg, intravenous, 10% as bolus and the remainder over 1 hour
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Modified Rankin Scale (mRS) 0-1
Time Frame: 3 months
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3 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Categorical shift in modified Rankin Score (mRS)
Time Frame: 3 months
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3 months
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Death due to any cause
Time Frame: 3 months
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3 months
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Reperfusion
Time Frame: 24 hours
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24 hours
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Recanalisation
Time Frame: 24 hours
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24 hours
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Recurrent stroke
Time Frame: 3 and 12 months
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3 and 12 months
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Change in ≥ 8 NIHSS points or reaching ≤ 1 on this scale
Time Frame: 3 months
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3 months
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Symptomatic ICH
Time Frame: 24 hours
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Symptomatic hemorrhage defined by SITS-MOST criteria: type 2 parenchymal hematoma associated with ≥4 point increase in NIHSS
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24 hours
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Infarct growth
Time Frame: 24 hours
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Difference in volumetric DWI volume between baseline and 24 hour MRI
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24 hours
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Depression (Montgomery-Asberg Depression Rating Scale [MADRS])
Time Frame: 3 and 12 months
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3 and 12 months
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Quality of life (Stroke Impact Scale)
Time Frame: 3 and 12 months
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3 and 12 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
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
- 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.
- 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. Erratum In: N Engl J Med. 2021 Apr 1;384(13):1278.
- 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.
- Goodin P, Lamp G, Vidyasagar R, Connelly A, Rose S, Campbell BCV, Tse T, Ma H, Howells D, Hankey GJ, Davis S, Donnan G, Carey LM. Correlated Resting-State Functional MRI Activity of Frontostriatal, Thalamic, Temporal, and Cerebellar Brain Regions Differentiates Stroke Survivors with High Compared to Low Depressive Symptom Scores. Neural Plast. 2019 Jul 28;2019:2357107. doi: 10.1155/2019/2357107. eCollection 2019.
- Tse T, Binte Yusoff SZ, Churilov L, Ma H, Davis S, Donnan GA, Carey LM; START research team. Increased work and social engagement is associated with increased stroke specific quality of life in stroke survivors at 3 months and 12 months post-stroke: a longitudinal study of an Australian stroke cohort. Top Stroke Rehabil. 2017 Sep;24(6):405-414. doi: 10.1080/10749357.2017.1318339. Epub 2017 Apr 24.
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
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NTA0901
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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