ANZCTR - Registration

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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]

HMRI2012101

Secondary ID [2]

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

Condition category

Condition code

Stroke

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]

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]

Proportion of patients with Modified Rankin Scale (mRS) 0-1 at 3 months (no disability).

Timepoint [1]

3 months

Secondary outcome [1]

Proportion of patients achieving a reduction of NIHSS = 8 and NIHSS = 4 or reaching 0-1 at 24-hour.

Timepoint [1]

24 hours post stroke

Secondary outcome [2]

Proportion of patients with Modified Rankin Scale 0-2 at 3-month (good clinical outcome).

Timepoint [2]

3 months

Secondary outcome [3]

Analysis of mRS across the full ordinal scale at 3-month.

Timepoint [3]

3 months

Secondary outcome [4]

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]

During time on study (3 months)

Secondary outcome [5]

Death due to any cause

Timepoint [5]

During time on study (3 months)

Secondary outcome [6]

Proportion of patients with Modified Rankin Scale (mRS) 5-6 at 3 months (severe disability or death).

Timepoint [6]

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?

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]

John Hunter Hospital Royal Newcastle Centre - New Lambton

Recruitment hospital [2]

Gosford Hospital - Gosford

Recruitment hospital [3]

Liverpool Hospital - Liverpool

Recruitment hospital [4]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [5]

Gold Coast Hospital - Southport

Recruitment hospital [6]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [7]

Box Hill Hospital - Box Hill

Recruitment hospital [8]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [9]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [10]

Sunshine Coast University Hospital - Birtinya

Recruitment hospital [11]

Sunshine Hospital - St Albans

Recruitment hospital [12]

Manning Rural Referral Hospital (Taree) - Taree

Recruitment hospital [13]

Tamworth Rural Referral Hospital - Tamworth

Recruitment hospital [14]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [15]

The Alfred - Prahran

Recruitment hospital [16]

St Vincent's Hospital (Melbourne) Ltd - Fitzroy

Recruitment postcode(s) [1]

2170 - Liverpool

Recruitment postcode(s) [2]

4006 - Herston

Recruitment postcode(s) [3]

4215 - Southport

Recruitment postcode(s) [4]

3052 - Parkville

Recruitment postcode(s) [5]

3128 - Box Hill

Recruitment postcode(s) [6]

3168 - Clayton

Recruitment postcode(s) [7]

5000 - Adelaide

Recruitment postcode(s) [8]

2305 - New Lambton Heights

Recruitment postcode(s) [9]

4575 - Birtinya

Recruitment postcode(s) [10]

3021 - St Albans

Recruitment postcode(s) [11]

2430 - Taree

Recruitment postcode(s) [12]

2340 - Tamworth

Recruitment postcode(s) [13]

4102 - Woolloongabba

Recruitment postcode(s) [14]

3004 - Prahran

Recruitment postcode(s) [15]

3065 - Fitzroy

Recruitment outside Australia

Country [1]

Taiwan, Province Of China

State/province [1]

Country [2]

United Kingdom

State/province [2]

England

Country [3]

Spain

State/province [3]

Barcelona

Country [4]

Belgium

State/province [4]

Flemish Brabant

Country [5]

New Zealand

State/province [5]

Christchurch

Country [6]

Finland

State/province [6]

Helsinki

Country [7]

Sweden

State/province [7]

Gothenburg

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council (NHMRC)

Address [1]

GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Greater Charitable Foundation

Address [2]

PO Box 173
Hamilton NSW 2303

Country [2]

Australia

Funding source category [3]

Charities/Societies/Foundations

Name [3]

National Heart Foundation of Australia

Address [3]

Unit 1,
Level 1,
17-23 Townshend St,
Phillip ACT 2606

Country [3]

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]

University

Name [1]

The University of Newcastle

Address [1]

University Drive
Callaghan NSW 2308

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Hunter New England Human Research Ethics Committee

Ethics committee address [1]

Locked Bag 1
New Lambton  NSW  2305

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

31/01/2013

Approval date [1]

11/04/2013

Ethics approval number [1]

HREC/13/HNE/23

Ethics committee name [2]

Human Research Ethics Committee (TQEH/LMH/MH)

Ethics committee address [2]

Basil Hetzel Institute DX465101
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South SA 5011

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

02/04/2014

Ethics approval number [2]

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

Attachments [1]

/AnzctrAttachments/363714-TASTE Lead HREC Approval letter 110413.pdf

Attachments [2]

/AnzctrAttachments/363714-HREC13TQEHLMH303Approval.pdf

Contacts

Principal investigator

Name

Prof Mark Parsons

Address

UNSW in the South West
Liverpool Hospital, Locked Bag 7103, LIVERPOOL BC NSW 1871 Australia

Country

Australia

Phone

+61287383847

Fax

+61287383850

[email protected]

Contact person for public queries

Name

Michelle Russell

Address

Department of Neurology
John Hunter Hospital
Locked Bag 1
HRMC NSW 2310

Country

Australia

Phone

+61 2 49213481

Fax

+61 2 4921 3488

[email protected]

Contact person for scientific queries

Name

Chris Levi

Address

Department of Neurology
John Hunter Hospital
Locked Bag 1
HRMC NSW 2310

Country

Australia

Phone

+61 2 87388864

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
17458	Study protocol			[email protected]

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Tenecteplase versus alteplase for thrombolysis in ... [More Details]

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically