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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
30/11/2023
Date data sharing statement initially provided
25/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE) Trial
Scientific title
A multicentre, prospective, randomised, open-label, blinded endpoint, controlled phase III non-inferiority trial with an with an adaptive sample size re-estimation in stroke thrombolysis patients to compare tenecteplase and alteplase.
Secondary ID [1] 281969 0
HMRI2012101
Secondary ID [2] 308262 0
NH&MRC APP1079696
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
Proportion of patients with Modified Rankin Scale (mRS) 0-1 at 3 months (no disability).
Timepoint [1] 288884 0
3 months
Secondary outcome [1] 301235 0
Proportion of patients achieving a reduction of NIHSS = 8 and NIHSS = 4 or reaching 0-1 at 24-hour.
Timepoint [1] 301235 0
24 hours post stroke
Secondary outcome [2] 301238 0
Proportion of patients with Modified Rankin Scale 0-2 at 3-month (good clinical outcome).
Timepoint [2] 301238 0
3 months
Secondary outcome [3] 301239 0
Analysis of mRS across the full ordinal scale at 3-month.
Timepoint [3] 301239 0
3 months
Secondary outcome [4] 301242 0
Proportion of patients with symptomatic intra-cerebral haemorrhage (sICH) defined as “Intracerebral haemorrhage (parenchymal haematoma type 2 - PH2 within 36 hours of treatment) combined with neurological deterioration leading to an increase of > 4 points on the NIHSS from baseline, or the lowest NIHSS value between baseline and 24 hours”
Timepoint [4] 301242 0
During time on study (3 months)
Secondary outcome [5] 301243 0
Death due to any cause
Timepoint [5] 301243 0
During time on study (3 months)
Secondary outcome [6] 301244 0
Proportion of patients with Modified Rankin Scale (mRS) 5-6 at 3 months (severe disability or death).
Timepoint [6] 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
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Intracranial haemorrhage (ICH) identified on baseline 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 one 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 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 two 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.
21. A known hypersensitivity to the active substance alteplase, tenecteplase, gentamicin or to any of the excipients.

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)
Patients will be randomised to receive tenecteplase or alteplase. A blocked randomisation procedure will be utilised to maximise the sequential balance. Patients will be treated with either alteplase or tenecteplase as per the on-line randomisation system.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

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), controlled phase III non-inferiority trial with an adaptive sample size re-estimation. Patients will be randomised 1:1 to standard dose IV tPA (0.9 mg/kg) or IV TNK (0.25 mg/kg).
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary analysis of the trial outcome will include both intention-to-treat and the per-protocol patient population as a non-inferiority analysis. Non-inferiority of tenecteplase will be established if the lower bound of 95% confidence interval (pooled across age and NIHSS strata) around the difference in proportions of patients with mRS 0-1 in tenecteplase and alteplase arms is greater than -0.03. If non-inferiority is established, superiority will be declared if the lower end of the above 95% confidence interval is greater than zero.

For the secondary superiority analyses, the proportions of mRS 0-1 vs 2-6 and mRS 0-2 vs 3-6 outcomes will be compared between tenecteplase and alteplase arms, adjusted for age and baseline NIHSS score using a mixed effect binary logistic regression model, with geographic region (Australia/New Zealand vs. Europe/Canada vs. Asia) as a random effect. Ordinal analysis of the mRS will also be undertaken on the full range (0-6) of the mRS using either assumption free Wilcoxon-Mann-Whitney Generalized Odds approach or mixed effect proportional odds logistic regression subject to the validity of proportional odds model assumptions. The proportions of patients achieving early clinical improvement will be compared between tenecteplase and alteplase arms, adjusted for age and baseline NIHSS score using a mixed effect binary logistic regression model with geographic region as a random effect. The proportions of patients with sICH will be compared between tenecteplase and alteplase arms using Fishers exact test or logistic regression as appropriate. The proportions of patients who died due to any cause will be compared between tenecteplase and alteplase arms adjusted for age and baseline NIHSS score using a mixed effect binary logistic regression model with geographic region as a random effect. The proportions of patients who have an mRS 5-6 vs 0-4 outcomes will be compared between tenecteplase and alteplase arms adjusted for age and baseline NIHSS score using a mixed effect binary logistic regression model with geographic region as a random effect.

A detailed Statistical Analysis Plan (SAP) will be developed prior to database lock.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
TNK non-inferior to tPA.
Date of first participant enrolment
Anticipated
1/05/2013
Actual
21/03/2014
Date of last participant enrolment
Anticipated
31/12/2024
Actual
19/10/2023
Date of last data collection
Anticipated
19/01/2024
Actual
Sample size
Target
832
Accrual to date
Final
680
Recruitment in Australia
Recruitment state(s)
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] 646 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 647 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [5] 649 0
Gold Coast Hospital - Southport
Recruitment hospital [6] 650 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [7] 651 0
Box Hill Hospital - Box Hill
Recruitment hospital [8] 654 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [9] 655 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [10] 8824 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [11] 8825 0
Sunshine Hospital - St Albans
Recruitment hospital [12] 23446 0
Manning Rural Referral Hospital (Taree) - Taree
Recruitment hospital [13] 23447 0
Tamworth Rural Referral Hospital - Tamworth
Recruitment hospital [14] 23448 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [15] 23449 0
The Alfred - Prahran
Recruitment hospital [16] 23450 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 6382 0
2170 - Liverpool
Recruitment postcode(s) [2] 6383 0
4006 - Herston
Recruitment postcode(s) [3] 6385 0
4215 - Southport
Recruitment postcode(s) [4] 6386 0
3052 - Parkville
Recruitment postcode(s) [5] 6387 0
3128 - Box Hill
Recruitment postcode(s) [6] 6390 0
3168 - Clayton
Recruitment postcode(s) [7] 6391 0
5000 - Adelaide
Recruitment postcode(s) [8] 6394 0
2305 - New Lambton Heights
Recruitment postcode(s) [9] 16948 0
4575 - Birtinya
Recruitment postcode(s) [10] 16949 0
3021 - St Albans
Recruitment postcode(s) [11] 38849 0
2430 - Taree
Recruitment postcode(s) [12] 38850 0
2340 - Tamworth
Recruitment postcode(s) [13] 38851 0
4102 - Woolloongabba
Recruitment postcode(s) [14] 38852 0
3004 - Prahran
Recruitment postcode(s) [15] 38853 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 6895 0
Taiwan, Province Of China
State/province [1] 6895 0
Country [2] 8111 0
United Kingdom
State/province [2] 8111 0
England
Country [3] 8112 0
Spain
State/province [3] 8112 0
Barcelona
Country [4] 9153 0
Belgium
State/province [4] 9153 0
Flemish Brabant
Country [5] 9154 0
New Zealand
State/province [5] 9154 0
Christchurch
Country [6] 25082 0
Finland
State/province [6] 25082 0
Helsinki
Country [7] 25083 0
Sweden
State/province [7] 25083 0
Gothenburg

Funding & Sponsors
Funding source category [1] 286785 0
Government body
Name [1] 286785 0
National Health and Medical Research Council (NHMRC)
Country [1] 286785 0
Australia
Funding source category [2] 289090 0
Charities/Societies/Foundations
Name [2] 289090 0
Greater Charitable Foundation
Country [2] 289090 0
Australia
Funding source category [3] 289091 0
Charities/Societies/Foundations
Name [3] 289091 0
National Heart Foundation of Australia
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
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
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
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 30 30 0 0
/AnzctrAttachments/363714-TASTE Lead HREC Approval letter 110413.pdf
Attachments [2] 31 31 0 0
/AnzctrAttachments/363714-HREC13TQEHLMH303Approval.pdf

Contacts
Principal investigator
Name 37914 0
Prof Mark Parsons
Address 37914 0
UNSW in the South West
Liverpool Hospital, Locked Bag 7103, LIVERPOOL BC NSW 1871 Australia
Country 37914 0
Australia
Phone 37914 0
+61287383847
Fax 37914 0
+61287383850
Email 37914 0
mark.parsons@health.nsw.gov.au
Contact person for public queries
Name 37915 0
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 49213481
Fax 37915 0
+61 2 4921 3488
Email 37915 0
michelle.russell@health.nsw.gov.au
Contact person for scientific queries
Name 37916 0
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 87388864
Fax 37916 0
Email 37916 0
christopher.levi@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol  michelle.russell@health.nsw.gov.au


Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.