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Trial registered on ANZCTR


Registration number
ACTRN12613000243718
Ethics application status
Approved
Date submitted
22/02/2013
Date registered
28/02/2013
Date last updated
17/08/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE) Trial
Scientific title
Multicentre, prospective, randomised open-label blinded endpoint (PROBE) phase III study in stroke thrombolysis patients to compare tenecteplase and alteplase for an outcome of less disability at 3 months.
Secondary ID [1] 281969 0
HMRI2012101
Universal Trial Number (UTN)
Trial acronym
TASTE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute ischaemic stroke 288396 0
Condition category
Condition code
Stroke 288742 288742 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Tenecteplase (TNK)
Dose: 0.25 mg/kg
Route: IV bolus injection
Frequency: once only, within 4.5 hours of stroke onset
Intervention code [1] 286536 0
Treatment: Drugs
Comparator / control treatment
Alteplase (tPA)
Dose: 0.9 mg/kg
Route: Intravenous (IV) infusion (10% as bolus and the remainder over 60 minutes)
Frequency: once only, within 4.5 hours of stroke onset
Control group
Active

Outcomes
Primary outcome [1] 288884 0
Modified Rankin Scale (mRS) 0-1 at 3 months (no disability).
Timepoint [1] 288884 0
3 months
Secondary outcome [1] 301233 0
Reperfusion at 24 hours post stroke. All patients will have a CT or MRI at 24 hours post treatment to assess for reperfusion.
Timepoint [1] 301233 0
24 hours post stroke
Secondary outcome [2] 301235 0
Early clinical improvement (reduction in acute – 24 hour NIHSS score)
Timepoint [2] 301235 0
24 hours post stroke
Secondary outcome [3] 301237 0
Modified Rankin Scale (mRS) 0-1 at 3 months (adjusted for baseline age and NIHSS)
Timepoint [3] 301237 0
3 months
Secondary outcome [4] 301238 0
Modified Rankin Scale 0-2
Timepoint [4] 301238 0
3 months
Secondary outcome [5] 301239 0
Categorical shift in mRS
Timepoint [5] 301239 0
3 months
Secondary outcome [6] 301240 0
Infarct growth. All patients will have CT or MRI at 24 hours post treatment to assess for infarct growth.
Timepoint [6] 301240 0
24 hours
Secondary outcome [7] 301241 0
Recanalisation. All patients will have CT or MRI at 24 hours post treatment to assess for recanalisation.
Timepoint [7] 301241 0
24 hours post stroke
Secondary outcome [8] 301242 0
Symptomatic intra-cerebral haemorrhage (sICH). All patients will have CT or MRI at 24 hours post treatment to assess for ICH.
Timepoint [8] 301242 0
During time on study (3 months)
Secondary outcome [9] 301243 0
Death due to any cause
Timepoint [9] 301243 0
During time on study (3 months)
Secondary outcome [10] 301244 0
Modified Rankin Scale (mRS) 5-6 (severe disability or death).
Timepoint [10] 301244 0
3 months

Eligibility
Key inclusion criteria
1. Patients presenting with acute hemispheric 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.

Imaging inclusion criteria:
1. Presence of penumbra - Using CTP or perfusion MR mismatch between the Tmax > 6 seconds delay perfusion volume and CTP relative cerebral blood flow (relCBF) or diffusion MR lesion infarct core volume
a) Mismatch ratio between Tmax perfusion lesion volume and infarct core lesion volume of > 1.8
b) Penumbra volume > 15 mL (Tmax lesion volume –infarct core lesion volume), and
2. Infarct core lesion volume < 70 mL. Note minimum slice coverage required for CTP will be 80 mm to prevent underestimation of infarct core volume with this modality.
3. Volume of severely hypoperfused tissue < 100mL (Tmax > 10 seconds delay or Delay Time > 8 seconds) indicative of poor response to reperfusion.
Minimum age
18 Years
Maximum age
No limit
Gender
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 greater than or equal to 2 (indicating previous disability).
4. Participation in any investigational study in the previous 30 days.
5. Any terminal illness such that patient would not be expected to survive more than 1 year.
6. 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.
7. Pregnant women.
8. Previous stroke within last three months.
9. 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.
10. Current use of vitamin K based oral anticoagulants (e.g. warfarin) and a prolonged prothrombin time (INR > 1.5).
11. Current use of novel oral anticoagulants (NOACs) (i.e. dabigatran, rivaroxaban, or apixiban).
12. 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.
13. 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.
14. Clinically significant hypoglycaemia.
15. 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.
16. Hereditary or acquired haemorrhagic diathesis.
17. Gastrointestinal or urinary bleeding within the preceding 21 days.
18. Major surgery within the preceding 14 days which poses risk in the opinion of the investigator.
19. Exposure to a thrombolytic agent within the previous 72 hours.
20. An extracranial or intracranial internal carotid artery occlusion or a proximal M1 middle cerebral artery occlusion which, in the judgment of the investigator, would be more appropriately treated with combined intravenous intra-arterial therapy, where the intra-arterial therapy can be accessed and delivered within a rapid time frame.

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 in the emergency department with acute ischemic stroke and are eligible for tPA therapy will be approached by a member of the research team and provided with a PIS/ICF. If consent is obtained, an online randomisation will occur and a treatment arm allocated. Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A block randomisation design will be used with stratifications for the size of baseline infarct core (less than or greater than 25 mL), and for the presence or absence of ICA occlusion.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Multicentre, prospective, randomised open-label blinded endpoint (PROBE) phase III study.
Patients will be randomised 1:1 to standard dose tPA (0.9 mg/kg) or TNK (0.25 mg/kg). There will be two randomisation strata: first, randomisation will be stratified by the presence or absence of internal carotid artery occlusion (ICAO) on baseline CT or MR angiography; second, randomisation will be stratified by size of infarct core (above or below 25 mL) on baseline CTP or diffusion-weighted MRI (DWI). Patients with ICAO will be capped at a maximum of 25% of the sample size.
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The primary efficacy analyses will be based on an intention-to-treat basis. The primary outcome will be compared using a two-sided significance test with alpha set at p = 0.05 (unadjusted).

For the secondary outcomes analysis, the proportions of mRS 0-1 outcomes will be compared between TNK and tPA arms adjusted for age and baseline NIHSS score using a binary logistic regression model. Analysis of the categorical shift in mRS will also be undertaken on the full range (0-6) of the mRS using Cochran-Mantel-Haenszel shift test and proportional odds logistic regression subject to the validity of shift analysis model assumptions. Other secondary outcome analyses will be carried out according to standard statistical principles for comparison of parametric or non-parametric distributions as appropriate.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC
Recruitment hospital [1] 600 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [2] 601 0
Gosford Hospital - Gosford
Recruitment hospital [3] 643 0
Westmead Hospital - Westmead
Recruitment hospital [4] 646 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 647 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [6] 649 0
Gold Coast Hospital - Southport
Recruitment hospital [7] 650 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [8] 651 0
Box Hill Hospital - Box Hill
Recruitment hospital [9] 654 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [10] 655 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [11] 2327 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [12] 8824 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [13] 8825 0
Sunshine Hospital - St Albans
Recruitment hospital [14] 8826 0
Calvary Public Hospital ACT - Bruce
Recruitment postcode(s) [1] 6378 0
2145 - Westmead
Recruitment postcode(s) [2] 6382 0
2170 - Liverpool
Recruitment postcode(s) [3] 6376 0
2250 - Gosford
Recruitment postcode(s) [4] 6394 0
2305 - New Lambton Heights
Recruitment postcode(s) [5] 16950 0
2617 - Bruce
Recruitment postcode(s) [6] 16949 0
3021 - St Albans
Recruitment postcode(s) [7] 6386 0
3052 - Parkville
Recruitment postcode(s) [8] 6387 0
3128 - Box Hill
Recruitment postcode(s) [9] 6390 0
3168 - Clayton
Recruitment postcode(s) [10] 8002 0
3220 - Geelong
Recruitment postcode(s) [11] 6383 0
4006 - Herston
Recruitment postcode(s) [12] 6385 0
4215 - Southport
Recruitment postcode(s) [13] 16948 0
4575 - Birtinya
Recruitment postcode(s) [14] 6391 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 6895 0
Taiwan, Province Of China
State/province [1] 6895 0
Country [2] 6896 0
Canada
State/province [2] 6896 0
Alberta
Country [3] 8111 0
United Kingdom
State/province [3] 8111 0
England
Country [4] 8112 0
Spain
State/province [4] 8112 0
Barcelona
Country [5] 9153 0
Belgium
State/province [5] 9153 0
Flemish Brabant
Country [6] 9154 0
New Zealand
State/province [6] 9154 0
Christchurch

Funding & Sponsors
Funding source category [1] 286785 0
Government body
Name [1] 286785 0
National Health and Medical Research Council (NHMRC)
Address [1] 286785 0
GPO Box 1421
Canberra ACT 2601
Country [1] 286785 0
Australia
Funding source category [2] 289090 0
Charities/Societies/Foundations
Name [2] 289090 0
Greater Charitable Foundation
Address [2] 289090 0
PO Box 173
Hamilton NSW 2303
Country [2] 289090 0
Australia
Funding source category [3] 289091 0
Charities/Societies/Foundations
Name [3] 289091 0
National Heart Foundation of Australia
Address [3] 289091 0
Unit 1,
Level 1,
17-23 Townshend St,
Phillip ACT 2606
Country [3] 289091 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Acute Stroke Service
Address
Department of Neurology
John Hunter Hospital
Locked Bag 1
HRMC NSW 2310
Country
Australia
Secondary sponsor category [1] 285568 0
University
Name [1] 285568 0
The University of Newcastle
Address [1] 285568 0
University Drive
Callaghan NSW 2308

Country [1] 285568 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288852 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 288852 0
Locked Bag 1
New Lambton NSW 2305
Ethics committee country [1] 288852 0
Australia
Date submitted for ethics approval [1] 288852 0
31/01/2013
Approval date [1] 288852 0
11/04/2013
Ethics approval number [1] 288852 0
HREC/13/HNE/23
Ethics committee name [2] 290877 0
Human Research Ethics Committee (TQEH/LMH/MH)
Ethics committee address [2] 290877 0
Basil Hetzel Institute DX465101
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South SA 5011
Ethics committee country [2] 290877 0
Australia
Date submitted for ethics approval [2] 290877 0
Approval date [2] 290877 0
02/04/2014
Ethics approval number [2] 290877 0
HREC/13/TQEHLMH/303

Summary
Brief summary
This research is comparing two clot dissolving medications tenecteplase and alteplase. Tenecteplase is not currently licensed and approved for use in acute stroke care, but has shown very promising results in recent stroke studies. Alteplase is the approved medication for ischaemic stroke. Despite the clear benefits of alteplase at reducing brain damage and disability, we would like to find a medication that has similar clot-dissolving effects with a lower risk of brain bleeding. This would result in an even greater reduction in long-term stroke disability.

The aim of this study is to compare alteplase with tenecteplase for stroke treatment to determine which will help more patients have less disability at 3 months following their stroke.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37914 0
Prof Neil Spratt
Address 37914 0
Department of Neurology
John Hunter Hospital
Locked Bag 1
HRMC NSW 2310
Country 37914 0
Australia
Phone 37914 0
61 2 4921 3490
Fax 37914 0
Email 37914 0
neil.spratt@hnehealth.nsw.gov.au
Contact person for public queries
Name 37915 0
Ms Michelle Russell
Address 37915 0
Department of Neurology
John Hunter Hospital
Locked Bag 1
HRMC NSW 2310
Country 37915 0
Australia
Phone 37915 0
+61 2 4921 3450
Fax 37915 0
+61 2 4921 3488
Email 37915 0
michelle.russell@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 37916 0
Prof Chris Levi
Address 37916 0
Department of Neurology
John Hunter Hospital
Locked Bag 1
HRMC NSW 2310
Country 37916 0
Australia
Phone 37916 0
+61 2 4921 3487
Fax 37916 0
Email 37916 0
christopher.levi@hnehealth.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
No Results