Trial registered on ANZCTR


Trial ID
ACTRN12608000466347
Ethics application status
Approved
Date submitted
2/09/2008
Date registered
17/09/2008
Type of registration
Prospectively registered

Titles & IDs
Public title
Low-dose tenecteplase versus standard-dose alteplase for acute ischaemic stroke: an Imaging-Based Efficacy Trial.
Scientific title
Low-dose tenecteplase versus standard-dose alteplase for acute ischaemic stroke: an Imaging-Based Efficacy Trial.
Secondary ID [1] 273177 0
Tenecteplase versus Alteplase for Acute Ischaemic Stroke (TAAIS) Trial
Universal Trial Number (UTN)
Trial acronym

Health condition
Health condition(s) or problem(s) studied:
Ischaemic stroke 3635 0
Condition category
Condition code
Neurological 3800 3800 0 0
Other neurological disorders
Stroke 3844 3844 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Tenecteplase: given as a single intravenous bolus (over one minute), in one of two doses (0.1mg/kg or 0.25 mg/kg)
Intervention code [1] 3348 0
Treatment: drugs
Comparator / control treatment
Alteplase: given intravenously 0.9mg/kg, 10% as a bolus (over one minute) and the remaining 90% as a one hour infusion immediately following the bolus
Control group
Active

Outcomes
Primary outcome [1] 4696 0
Reperfusion: This will be measured by the proportional reduction in the size of the pre-treatment perfusion lesion (mean transit time) on perfusion computed tomography (CTP) or magnetic resonance imaging (MRI), and the 24 hour post-treatment MRI perfusion lesion.
Timepoint [1] 4696 0
Baseline and 24 hours
Primary outcome [2] 4697 0
Early Clinical Improvement: This will be determined by change in the NIHSS (National Institutes of Health Stroke Scale) score from pre-treatment to 24 hours.
Timepoint [2] 4697 0
Baseline and 24 hours
Secondary outcome [1] 7916 0
Intra-cranial haemorrhage (ICH): Proportion with parenchymal haematoma (PH type 1 or PH type 2) on 24 hour MRI
Timepoint [1] 7916 0
24 hours
Secondary outcome [2] 7917 0
Proportion with parenchymal haematoma type 2 (PH2) on 24 hour MRI
Timepoint [2] 7917 0
Baseline and 24 hour perfusion CT and MRI
Secondary outcome [3] 7918 0
Proportion with complete vessel recanalisation on 24 hour MRA
Timepoint [3] 7918 0
24 hours
Secondary outcome [4] 7919 0
Infarct growth between acute CTP and 24 hour MRI - measured in absolute volume change (mL)
Timepoint [4] 7919 0
baseline and 24 hours
Secondary outcome [5] 7920 0
Infarct growth between acute CTP and day 90 MRI - measured in absolute volume change (mL)
Timepoint [5] 7920 0
Baseline and day 90
Secondary outcome [6] 7921 0
Proportion with early major neurologic improvement at 24 hours (NIHSS reduction of 8 or more)
Timepoint [6] 7921 0
Baseline and 24 hours
Secondary outcome [7] 7922 0
Proportion with good functional outcome: defined as a modified Rankin Scale (mRS) of 0-2
Timepoint [7] 7922 0
day 90
Secondary outcome [8] 294368 0
Proportion of patients with symptomatic ICH (PH2 + decline of 4 or more points on NIHSS) at 24 hours
Timepoint [8] 294368 0
24 hours
Secondary outcome [9] 294369 0
Proportion of patients with excellent functional outcome: defined as a modified Rankin Scale (mRS) of 0-1 at 90 days
Timepoint [9] 294369 0
90 days
Secondary outcome [10] 294370 0
Proportion of patients with poor functional outcome: defined as a modified Rankin Scale (mRS) of 5-6 at 90 days
Timepoint [10] 294370 0
90 days
Secondary outcome [11] 294371 0
Proportional reperfusion at 24 hours (non-parametric measured)
Timepoint [11] 294371 0
24 hours
Secondary outcome [12] 294372 0
Proportion of patients with complete or partial recanalisation on MRA (MR angiogram) at 24 hours.
Timepoint [12] 294372 0
24 hours
Secondary outcome [13] 294373 0
Change in acute to 24 hour NIHSS (non-parametric measured)
Timepoint [13] 294373 0
24 hours
Secondary outcome [14] 294374 0
Proportion of patients dying before 90 days
Timepoint [14] 294374 0
90 days
Secondary outcome [15] 294375 0
The above analyses will be performed on pooled TNK vs tPA group. Should there be significant differences in the primary outcomes the above analyses will be repeated between the individual treatment groups
Timepoint [15] 294375 0
24 hours and 90 days

Eligibility
Key inclusion criteria
Patients presenting with acute ischaemic stroke, onset within previous 6 hours. Fulfilling usual clinical criteria for thrombolytic treatment. Specific additional advanced imaging criteria:

Imaging inclusion criteria:
CT or MR scanning has excluded intracranial haemorrhage
CT angiography (CTA) shows a visible vessel occlusion (complete or partial) – this may be in middle, anterior or posterior cerebral artery, and should be anatomically correlated with the perfusion CT (CTP) lesion
CTP or MRI shows >20% ‘mismatch’ between mean transit time (MTT) lesion and cerebral blood volume (CBV) or DWI lesion (i.e. significant penumbral tissue) – this is visually assessed.
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Standard clinical exclusion criteria for stroke thrombolysis apply.
Specific imaging exclusion criteria:
Severe renal impairment - Glomerular filtration rate (GFR) <15 mls/min
Contraindication to MRI (pacemaker, aneurysm clips)
No perfusion lesion visible and/or no visible vessel occlusion (in middle, anterior, or posterior cerebral arteries)
‘Match’ between cerebral blood volume (CBV) or diffusion-weighted MRI (DWI) lesion and MTT lesion (i.e. no penumbra).
Large area of irreversible ischaemia (>1/3 middle cerebral artery territory on CBV, or DWI)
Internal carotid occlusion on side of acutely affected hemisphere or carotid ‘T’ thrombus (as this may be more effectively treated with intra-arterial therapy)
Evidence of acute brainstem ischaemia

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)
Treatment allocation is via a centralised telephone service, manned by the central study coordinator. Treatment allocation occurs via phone call to the central study coordinator who opens a sealed opaque envelope envelope (next in sequence) and informs the investigator of the allocation. The only person who has access to the sealed opaque envelopes (locked in a filing cabinet) is the central study coordinator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy

Recruitment
Anticipated date of first participant enrolment
1/11/2008
Actual date of first participant enrolment
Anticipated date last participant enrolled
Actual date last participant enrolled
Target sample size
75
Actual sample size
Recruitment status
Recruiting
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 1127 0
2305
Recruitment postcode(s) [2] 1128 0
3128
Recruitment postcode(s) [3] 1129 0
3084
Recruitment postcode(s) [4] 1130 0
3052

Funding & Sponsors
Funding source category [1] 3813 0
Government body
Name [1] 3813 0
National Health and Medical Research Council (NHMRC) Project Grant: ID 510722
Address [1] 3813 0
Level 5, 20 Allara Street
Canberra ACT 2601
Country [1] 3813 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital, University of Newcastle
Address
1 Lookout Road
New Lambton Heights, Newcastle, NSW 2305
Country
Australia
Secondary sponsor category [1] 3422 0
None
Name [1] 3422 0
Address [1] 3422 0
Country [1] 3422 0
Other collaborator category [1] 395 0
Hospital
Name [1] 395 0
Box Hill Hospital
Address [1] 395 0
1 Nelson Road
Box Hill Melbourne, VIC 3128
Country [1] 395 0
Australia
Other collaborator category [2] 396 0
Hospital
Name [2] 396 0
Austin Hospital
Address [2] 396 0
145 Studley Road
Heidelberg Melbourne VIC 3084
Country [2] 396 0
Australia
Other collaborator category [3] 397 0
Hospital
Name [3] 397 0
Royal Melbourne Hospital
Address [3] 397 0
Corner Grattan Street and Sydney Road
Parkville, Melbourne, VIC 3050
Country [3] 397 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5939 0
Eastern Health Research and Ethics Committee
Ethics committee address [1] 5939 0
16 Arnold Street
Box Hill
VIC 3128
Ethics committee country [1] 5939 0
Australia
Date submitted for ethics approval [1] 5939 0
Approval date [1] 5939 0
12/09/2008
Ethics approval number [1] 5939 0
E07/0809

Summary
Brief summary
This is a trial of thrombolytic (clot-dissolving) treatment for acute stroke comparing the standard medication alteplase to a newer agent, tenecteplase
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28894 0
Address 28894 0
Country 28894 0
Phone 28894 0
Fax 28894 0
Email 28894 0
Contact person for public queries
Name 12051 0
Dr Mark Parsons
Address 12051 0
Department of Neurology
John Hunter Hospital
1 Lookout Road
New Lambton Heights
NSW 2305
Country 12051 0
Australia
Phone 12051 0
+61249213490
Fax 12051 0
Email 12051 0
mark.parsons@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 2979 0
Dr Mark Parsons
Address 2979 0
Department of Neurology
John Hunter Hospital
1 Lookout Road
New Lambton Heights
NSW 2305
Country 2979 0
Australia
Phone 2979 0
+61249213490
Fax 2979 0
Email 2979 0
mark.parsons@hnehealth.nsw.gov.au