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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00887328




Registration number
NCT00887328
Ethics application status
Date submitted
22/04/2009
Date registered
23/04/2009
Date last updated
31/08/2018

Titles & IDs
Public title
Extending the Time for Thrombolysis in Emergency Neurological Deficits
Scientific title
Extending the Time for Thrombolysis in Emergency Neurological Deficits
Secondary ID [1] 0 0
NTA0901
Universal Trial Number (UTN)
Trial acronym
EXTEND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tissue Plasminogen Activator (Alteplase)
Treatment: Drugs - Placebo

Experimental: IV tPA - intravenous tissue plasminogen activator

Placebo Comparator: Placebo -


Treatment: Drugs: Tissue Plasminogen Activator (Alteplase)
0.9 mg/kg up to a maximum of 90mg, intravenous, 10% as bolus and the remainder over 1 hour

Treatment: Drugs: Placebo
placebo provided as 50mg lyophilised powder to be reconstituted with sterile water in glass vials indistinguishable from active drug
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Modified Rankin Scale (mRS) 0-1
Timepoint [1] 0 0
3 months
Secondary outcome [1] 0 0
Categorical shift in modified Rankin Score (mRS)
Timepoint [1] 0 0
3 months
Secondary outcome [2] 0 0
Change in = 8 NIHSS points or reaching = 1 on this scale
Timepoint [2] 0 0
3 months
Secondary outcome [3] 0 0
Death due to any cause
Timepoint [3] 0 0
3 months
Secondary outcome [4] 0 0
Symptomatic ICH
Timepoint [4] 0 0
24 hours
Secondary outcome [5] 0 0
Reperfusion
Timepoint [5] 0 0
24 hours
Secondary outcome [6] 0 0
Recanalisation
Timepoint [6] 0 0
24 hours
Secondary outcome [7] 0 0
Infarct growth
Timepoint [7] 0 0
24 hours
Secondary outcome [8] 0 0
Recurrent stroke
Timepoint [8] 0 0
3 and 12 months
Secondary outcome [9] 0 0
Depression (Montgomery-Asberg Depression Rating Scale [MADRS])
Timepoint [9] 0 0
3 and 12 months
Secondary outcome [10] 0 0
Quality of life (Stroke Impact Scale)
Timepoint [10] 0 0
3 and 12 months

Eligibility
Key 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
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, 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

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/08/2018
Sample size
Target
Accrual to date
Final
180
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Gosford Hospital - Kanwal
Recruitment hospital [2] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [4] 0 0
St. Vincent's Hospital - Sydney
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment hospital [6] 0 0
Royal Brisbane & Women's Hospital - Brisbane
Recruitment hospital [7] 0 0
Gold Coast University Hospital - Gold Coast
Recruitment hospital [8] 0 0
Sunshine Coast University Hospital - Nambour
Recruitment hospital [9] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [10] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [11] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [12] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [13] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [14] 0 0
Western Hospital - Footscray
Recruitment hospital [15] 0 0
Geelong Hospital - Geelong
Recruitment hospital [16] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [17] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [18] 0 0
Epworth Healthcare - Richmond
Recruitment hospital [19] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [20] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2259 - Kanwal
Recruitment postcode(s) [2] 0 0
- Newcastle
Recruitment postcode(s) [3] 0 0
2065 - St. Leonards
Recruitment postcode(s) [4] 0 0
6009 - Sydney
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment postcode(s) [6] 0 0
4029 - Brisbane
Recruitment postcode(s) [7] 0 0
- Gold Coast
Recruitment postcode(s) [8] 0 0
4560 - Nambour
Recruitment postcode(s) [9] 0 0
5000 - Adelaide
Recruitment postcode(s) [10] 0 0
5042 - Bedford Park
Recruitment postcode(s) [11] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [12] 0 0
3128 - Box Hill
Recruitment postcode(s) [13] 0 0
3168 - Clayton
Recruitment postcode(s) [14] 0 0
3011 - Footscray
Recruitment postcode(s) [15] 0 0
3220 - Geelong
Recruitment postcode(s) [16] 0 0
- Heidelberg
Recruitment postcode(s) [17] 0 0
3050 - Melbourne
Recruitment postcode(s) [18] 0 0
3121 - Richmond
Recruitment postcode(s) [19] 0 0
6009 - Nedlands
Recruitment postcode(s) [20] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
Finland
State/province [1] 0 0
Helsinki
Country [2] 0 0
New Zealand
State/province [2] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
Neuroscience Trials Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Commonwealth Scientific and Industrial Research Organisation, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University of Melbourne
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Melbourne Health
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
The Florey Institute of Neuroscience and Mental Health
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00887328
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Geoffrey Donnan, MD FRACP
Address 0 0
The Florey Institute of Neuroscence and Mental Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00887328