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Trial registered on ANZCTR


Registration number
ACTRN12611000969965
Ethics application status
Approved
Date submitted
9/09/2011
Date registered
9/09/2011
Date last updated
12/03/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
EXTEND-IA: Extending the time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial, a randomised trial of clot retrieval after intravenous thrombolysis in ischemic stroke
Scientific title
A randomized controlled trial of intra-arterial reperfusion therapy after standard dose intravenous t-PA within 4.5 hours of ischemic stroke onset utilizing dual target vessel occlusion and penumbral mismatch imaging selection
Secondary ID [1] 280450 0
ClinicalTrials.gov NCT01492725
Universal Trial Number (UTN)
U1111-1124-4509
Trial acronym
EXTEND-IA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischemic stroke 270740 0
Condition category
Condition code
Stroke 270917 270917 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intra-arterial mechanical clot retrieval with the Solitaire device after patients have received standard therapy with intravenous tissue plasminogen activator (tPA). Clot retrieval involves cerebral angiography and takes approximately 2 hours.
Intervention code [1] 269359 0
Treatment: Devices
Comparator / control treatment
Standard dose 0.9mg/kg (max 90mg) intravenous tissue plasminogen activator (tPA) administered once as a bolus (10%) followed by infusion over 1 hour (90%).
Control group
Active

Outcomes
Primary outcome [1] 279586 0
Reperfusion at 24 hours (CT or MR perfusion imaging)
Timepoint [1] 279586 0
24 hours post stroke onset
Primary outcome [2] 279587 0
Favourable clinical response (National Institutes of Health Stroke Score - NIHSS - reduction >/= 8 points or reaching 0-1) at 3 days
Timepoint [2] 279587 0
3 days post stroke onset
Secondary outcome [1] 287968 0
Reperfusion at 24 hrs post stroke without symptomatic intracerebral hemorrhage (CT or MR perfusion imaging)
Timepoint [1] 287968 0
24 hours post stroke onset
Secondary outcome [2] 287969 0
Recanalisation at 24 hrs post stroke (CT or MR angiography)
Timepoint [2] 287969 0
24 hours post stroke onset
Secondary outcome [3] 287970 0
Infarct growth within 24 hrs (CT and MRI)
Timepoint [3] 287970 0
24 hours post stroke onset
Secondary outcome [4] 287971 0
Stroke severity (NIHSS) at 24 hours
Timepoint [4] 287971 0
24 hours post stroke onset
Secondary outcome [5] 287972 0
Symptomatic intra-cranial hemorrhage (ECASS type 2 parenchymal hematoma on CT or MRI combined with >/=4 point deterioration in NIHSS within 36 hours of treatment).
Timepoint [5] 287972 0
within 36 hours of intervention
Secondary outcome [6] 287973 0
Death due to any cause
Timepoint [6] 287973 0
3 months
Secondary outcome [7] 287974 0
Modified Rankin Scale (mRS) 0-1 at 3 months
Timepoint [7] 287974 0
3 months
Secondary outcome [8] 287975 0
Categorical shift in mRS at 3 months
Timepoint [8] 287975 0
3 months
Secondary outcome [9] 287976 0
NIHSS reduction 8 points or reaching 0-1 at 3 months
Timepoint [9] 287976 0
3 months
Secondary outcome [10] 297344 0
Modified Rankin Scale (mRS) 0-2 at 3 months
Timepoint [10] 297344 0
3 months

Eligibility
Key inclusion criteria
1. Patients presenting with anterior circulation acute ischaemic stroke eligible using standard criteria to receive IV tPA within 4.5 hours of stroke onset
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. Intra-arterial clot retrieval treatment can commence (groin puncture) within 6 hours of stroke onset.
Imaging inclusion criteria
Dual target:
5. Arterial occlusion on CTA or MRA of the ICA, M1 or M2
6. Mismatch - Using CT or MRI with a Tmax >6 second delay perfusion volume and either CT-rCBF or DWI infarct core volume.
a) Mismatch ratio of greater than 1.2, and
b) Absolute mismatch volume of greater than 10 ml, and
c) Infarct core lesion volume of less than 70mL
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Intracranial haemorrhage (ICH) identified by CT or MRI
2. Rapidly improving symptoms at the discretion of the investigator
3. Pre-stroke mRS score of >/= 2 (indicating previous disability)
4. Inability to access the cerebral vasculature in the opinion of the neurointerventional team
5. Contra indication to imaging with MR with contrast agents
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, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
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 a prolonged activated 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 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients presenting to the emergency department with acute ischaemic stroke, who are eligible for standard intravenous tPA therapy within 4.5 hours of stroke onset will be assessed for “dual target” major vessel occlusion and mismatch to determine their eligibility for randomisation into the trial. If the patient gives informed consent they will be randomised 50:50 using central computerised allocation to intra-arterial clot retrieval after IV tPA or IV tPA alone. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization scheme will be based on permuted blocks to promote both group and sequential balance. Randomized patients will be stratified by site of baseline arterial occlusion into one of three groups:
1. Internal carotid artery (ICA) occlusion
2. Proximal middle cerebral artery (MCA – M1) occlusion
3. Distal middle cerebral artery (MCA – M2) occlusion
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
1/06/2012
Actual
1/08/2012
Date of last participant enrolment
Anticipated
Actual
13/10/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment outside Australia
Country [1] 3833 0
New Zealand
State/province [1] 3833 0

Funding & Sponsors
Funding source category [1] 269817 0
Government body
Name [1] 269817 0
NHMRC
Country [1] 269817 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Florey Institute of Neuroscience and Mental Health
Address
Melbourne Brain Centre
245 Burgundy Street
Heidelberg, VIC 3084
Country
Australia
Secondary sponsor category [1] 268849 0
None
Name [1] 268849 0
Address [1] 268849 0
Country [1] 268849 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271785 0
Melbourne Health
Ethics committee address [1] 271785 0
Royal Melbourne Hospital
Grattan St
Parkville VIC 3050
Ethics committee country [1] 271785 0
Australia
Date submitted for ethics approval [1] 271785 0
23/09/2011
Approval date [1] 271785 0
10/11/2011
Ethics approval number [1] 271785 0
HREC/11/MH/247

Summary
Brief summary
A prospective, randomised, open-label, blinded endpoint phase II trial to test the hypothesis that anterior circulation ischaemic stroke patients, selected with “dual target” vessel occlusion and CT or MRI mismatch within 4.5 hours of onset will have improved reperfusion and early neurological improvement when treated with intra-arterial clot retrieval (Solitaire device) after intravenous tPA, compared to intravenous tPA alone. Planned recruitment of 100 patients, randomised 50:50 at approximately 12 centres in Australia and New Zealand.
Trial website
NA
Trial related presentations / publications
NA
Public notes

Contacts
Principal investigator
Name 33136 0
Dr Bruce Campbell
Address 33136 0
Royal Melbourne Hospital Grattan St Parkville VIC 3050
Country 33136 0
Australia
Phone 33136 0
+61 3 9342 7000
Fax 33136 0
+61 3 9342 8427
Email 33136 0
bruce.campbell@mh.org.au
Contact person for public queries
Name 16383 0
Dr Bruce Campbell
Address 16383 0
Royal Melbourne Hospital
Grattan St
Parkville VIC 3050
Country 16383 0
Australia
Phone 16383 0
+61 3 9342 7000
Fax 16383 0
+61 3 9342 8427
Email 16383 0
bruce.campbell@mh.org.au
Contact person for scientific queries
Name 7311 0
Dr Bruce Campbell
Address 7311 0
Royal Melbourne Hospital
Grattan St
Parkville VIC 3050
Country 7311 0
Australia
Phone 7311 0
+61 3 9342 7000
Fax 7311 0
+61 3 9342 8427
Email 7311 0
bruce.campbell@mh.org.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEndovascular therapy for ischemic stroke with perfusion-imaging selection.2015https://dx.doi.org/10.1056/NEJMoa1414792
N.B. These documents automatically identified may not have been verified by the study sponsor.