- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01580839
EXTEND (International): Extending the Time for Thrombolysis in Emergency Neurological Deficits (International) (EXTEND)
August 30, 2018 updated by: Neuroscience Trials Australia
Extending the Time for Thrombolysis in Emergency Neurological Deficits
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
45
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
-
-
-
Taichung, Taiwan, 40447
- China Medical University 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:
- 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
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: 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:
|
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
|
|
Change in ≥ 8 National Institutes of Health Stroke Scale (NIHSS) points or reaching ≤ 1 on this scale
Time Frame: 3 months
|
3 months
|
|
Death due to any cause
Time Frame: 3 months
|
3 months
|
|
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
|
24 hours
|
Reperfusion
Time Frame: 24 hours
|
24 hours
|
|
Recanalisation
Time Frame: 24 hours
|
24 hours
|
|
Infarct growth
Time Frame: 24 hours
|
Difference in volumetric Diffusion Weighted Image (DWI) volume between baseline and 24 hour Magnetic Resonance Imaging (MRI)
|
24 hours
|
Recurrent stroke
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.
Sponsor
Collaborators
Investigators
- Principal Investigator: Geoffrey Donnan, MD FRACP, The Florey Institute of Neuroscience and Mental Health
- Principal Investigator: Stephen Davis, MD FRACP, University of Melbourne
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.
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 (Actual)
December 6, 2012
Primary Completion (Actual)
August 22, 2018
Study Completion (Actual)
August 22, 2018
Study Registration Dates
First Submitted
April 17, 2012
First Submitted That Met QC Criteria
April 17, 2012
First Posted (Estimate)
April 19, 2012
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
- NTA0903
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
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.
Clinical Trials on Stroke
-
University Hospital, GhentRecruitingStroke | Stroke, Ischemic | Stroke, Acute | Stroke Sequelae | Stroke HemorrhagicBelgium
-
Moleac Pte Ltd.RecruitingStroke | Stroke, Ischemic | Stroke Sequelae | Stroke, Cardiovascular | Strokes Thrombotic | Stroke, Embolic | Stroke, CryptogenicSingapore, Philippines
-
Moleac Pte Ltd.Not yet recruitingStroke | Stroke, Ischemic | Stroke Sequelae | Stroke, Cardiovascular | Strokes Thrombotic | Stroke, Embolic | Stroke, Cryptogenic
-
IRCCS San Camillo, Venezia, ItalyRecruitingStroke | Stroke, Ischemic | Stroke Sequelae | Stroke HemorrhagicItaly
-
Vanderbilt University Medical CenterPatient-Centered Outcomes Research Institute; University of Alabama at BirminghamEnrolling by invitationStroke | Stroke, Ischemic | Stroke, Acute | Stroke Sequelae | Engagement, Patient | Stroke HemorrhagicUnited States
-
University of MinnesotaAmerican Occupational Therapy FoundationRecruitingStroke | Stroke Sequelae | Stroke Hemorrhagic | Stroke IschemicUnited States
-
University of British ColumbiaCanadian Institutes of Health Research (CIHR); Michael Smith Foundation for...RecruitingStroke | Stroke, Ischemic | Stroke Hemorrhagic | Chronic StrokeCanada
-
University of CincinnatiMedical University of South Carolina; University of California, Los Angeles; University...RecruitingStroke | Stroke, Ischemic | Stroke, Acute | Stroke HemorrhagicUnited States
-
Turkish Stroke Research and Clinical Trials NetworkElectroCore INC; Turkish Neurological SocietyCompletedStroke | Stroke, Ischemic | Stroke, Acute | Stroke, HemorrhagicTurkey
-
University of LiegeCompletedStroke, Acute | Stroke Hemorrhagic | Stroke, ComplicationBelgium
Clinical Trials on Tissue Plasminogen Activator (Alteplase)
-
Xuanwu Hospital, BeijingRecruitingAcute Ischemic Stroke | Arterial Thrombosis | Posterior Circulation Brain InfarctionChina
-
Thomas Jefferson UniversityGenentech, Inc.Unknown
-
The University of Texas Health Science Center,...Genentech, Inc.CompletedIschemic StrokeUnited States
-
Washington University School of MedicineMassachusetts General Hospital; National Heart, Lung, and Blood Institute (NHLBI) and other collaboratorsCompletedVenous Thrombosis | Deep Vein Thrombosis | Postphlebitic Syndrome | Venous Thromboembolism | Post Thrombotic SyndromeUnited States
-
Hospital Clinic of BarcelonaFundacion Clinic per a la Recerca Biomédica; Fundació La Marató de TV3Completed
-
Penumbra Inc.Completed
-
Mazandaran University of Medical SciencesCompletedMortality | Stroke, Acute | Thrombolytic Therapy | AlteplaseIran, Islamic Republic of
-
South West Sydney Local Health DistrictRecruitingAcute Respiratory Failure | Hypercoagulability | Fibrinolysis ShutdownAustralia
-
Neuroscience Trials AustraliaMelbourne Health; University of Melbourne; Commonwealth Scientific and Industrial... and other collaboratorsCompletedStrokeAustralia, Finland, New Zealand
-
Second Affiliated Hospital, School of Medicine,...RecruitingStroke, Acute IschemicChina