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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02398656




Registration number
NCT02398656
Ethics application status
Date submitted
20/03/2015
Date registered
25/03/2015

Titles & IDs
Public title
A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion
Scientific title
Multicentre, Prospective Randomized Open Label, Blinded-endpoint (PROBE) Controlled Trial of Thrombolysis With Low Dose Tenecteplase (TNK-tPA) Versus Standard of Care in Minor Ischemic Stroke With Proven Acute Symptomatic Occlusion
Secondary ID [1] 0 0
Version 3.3 , Mar 24,2017
Universal Trial Number (UTN)
Trial acronym
TEMPO-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke, Acute 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tenecteplase
Treatment: Drugs - Antiplatelet treatment

Experimental: Tenecteplase (tNK) - Experimental: TNK-tPA (0.25mg/kg) given as a single, intravenous bolus immediately upon randomization. Experimental treatment will be administered as a single intravenous bolus over 1-2 minutes as per the standard manufacturers' instructions for use. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor than alteplase.

Active comparator: Control (Antiplatelet Agents) - Control: Patients will be treated with standard of care based antiplatelet treatment - choice at the discretion of the investigator. Low dose aspirin (single agent) will be the choice of most physicians, some will chose to use the combination of aspirin and clopidogrel. As this is a multi-centre, international trial where local practices will vary, rather than mandating a specific antiplatelet agent, we will allow the local investigator to chose which antithrombotic regime should be used. Standard of care medication(s) should be given immediately upon randomization.


Treatment: Drugs: Tenecteplase
TNK will be administered as a single intravenous bolus over 1-2 minutes within 90 minutes of the CT scan.

Treatment: Drugs: Antiplatelet treatment
Low dose aspirin (single agent) will be the choice of most physicians, some Investigators will chose to use the combination of aspirin and clopidogrel.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Modified Rankin Scale (mRS)
Timepoint [1] 0 0
90 Days
Secondary outcome [1] 0 0
Major Bleeding
Timepoint [1] 0 0
90 Days

Eligibility
Key inclusion criteria
1. Acute ischemic stroke in an adult patient (18 years of age or older)
2. Onset (last-seen-well) time to treatment time = 12 hours.
3. TIA or minor stroke defined as a baseline NIHSS = 5 at the time of randomization. Patients do not have to have persistent demonstrable neurological deficit on physical neurological examination.
4. Any acute intracranial occlusion or near occlusion (TICI 0 or 1) (MCA, ACA, PCA, VB territories) defined by non-invasive acute imaging (CT angiography or MR angiography) that is neurologically relevant to the presenting symptoms and signs. Multiphase CTA or CT perfusion are required for this study. An acute occlusion is defined as TICI 0 or TICI 1 flow.1 Practically this can include a small amount of forward flow in the presence of a near occlusion AND, Delayed washout of contrast with pial vessels on multiphase CTA in a region of brain concordant with clinical symptoms and signs OR, Any area of focal perfusion abnormality identified using CT or MR perfusion - e.g. transit delay (TTP, MTT or T Max), in a region of brain concordant with clinical symptoms and signs.
5. Pre-stroke independent functional status - structured mRS =2.
6. Informed consent from the patient or surrogate.
7. Patients can be treated within 90 minutes of the first slice of CT or MRI. Scans can be repeated to meet this requirement; if there is no change neurologically then only a CT head need be repeated for assessment of extent and depth of ischemia.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Hyperdensity on NCCT consistent with intracranial hemorrhage.
2. Large acute stroke ASPECTS < 7 visible on baseline CT scan.
3. Core of established infarction. No large area (estimated > 10 cc) of grey matter hypodensity at a similar density to white matter or in the judgment of the enrolling neurologist is consistent with a subacute ischemic stroke > 12 hours of age.
4. Clinical history, past imaging or clinical judgment suggest that that intracranial occlusion is chronic.
5. Patient has a severe or fatal or disabling illness that will prevent improvement or follow-up or such that the treatment would not likely benefit the patient.
6. Pregnancy
7. Planned thrombolysis with IV tPA or endovascular thrombolysis/thrombectomy treatment.
8. In-hospital stroke unless these patients are at their baseline prior to their stroke. E.g. a patient who had a stroke during a diagnostic coronary angiogram.
9. Commonly accepted exclusions for medical thrombolytic treatment. These are commonly relative contraindications (i.e. the final decision is at the discretion of the treating physician) but for the purposes of TEMPO-2 include the following:

* International normalized ratio > 1.7 or known full anticoagulation with use of any standard or direct oral anticoagulant therapy with full anticoagulant dosing. [DVT prophylaxis dosing shall not prohibit enrolment]. For low molecular weight heparins (LMWH) more than 48 hours off drug will be considered sufficient to allow trial enrollment. For direct oral anticoagulants; in patients with normal renal function more than 48 hours off drug will be considered sufficient to allow trial enrollment. Patients on direct oral anticoagulants who have any degree of renal impairment should not be enrolled in the trial unless they have not taken a dose of the drug in the last 5 days. Dual antiplatelet therapy does not prohibit enrolment.
* Dual antiplatelet therapy does not prohibit enrolment. [For patients who are known not to be taking anticoagulant therapy it is not necessary to wait for coagulation lab results (e.g. PT, PTT) prior to treatment]
* Patients who have been acutely treated with GP2b3a inhibitors.
* Arterial puncture at a non-compressible site in the previous seven days
* Clinical stroke or serious head or spinal trauma in the preceding three months that would normally preclude use of a thrombolytic agent.
* History of intracranial hemorrhage, subarachnoid hemorrhage or other brain hemorrhage that would normally preclude use of a thrombolytic agent.
* Major surgery within the last 3 months at a bodily site where bleeding could result in serious harm or death.
* Known platelet count below 100,000 per cubic millimeter. Treatment should not be delayed to wait for platelet count unless thrombocytopenia is known or suspected.
* Gastrointestinal or genitourinary bleeding within the past 3 months that is unresolved or associated with persisting anemia such that thrombolytic treatment of any kind would result in serious bleeding or death.

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 assessing the outcomes
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
1/04/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/04/2024
Sample size
Target
Accrual to date
Final
886
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Calvary Public Hospital Bruce - Canberra
Recruitment hospital [2] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [3] 0 0
Gold Coast University Hospital - Gold Coast
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [6] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [7] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
- Canberra
Recruitment postcode(s) [2] 0 0
- Newcastle
Recruitment postcode(s) [3] 0 0
- Gold Coast
Recruitment postcode(s) [4] 0 0
- Adelaide
Recruitment postcode(s) [5] 0 0
- Box Hill
Recruitment postcode(s) [6] 0 0
- Melbourne
Recruitment postcode(s) [7] 0 0
- Murdoch
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Vienna
Country [2] 0 0
Brazil
State/province [2] 0 0
Botucatu
Country [3] 0 0
Brazil
State/province [3] 0 0
Brasília
Country [4] 0 0
Brazil
State/province [4] 0 0
Campo Grande
Country [5] 0 0
Brazil
State/province [5] 0 0
Celso Ramos
Country [6] 0 0
Brazil
State/province [6] 0 0
Fortaleza
Country [7] 0 0
Brazil
State/province [7] 0 0
Joinville
Country [8] 0 0
Brazil
State/province [8] 0 0
Porto Alegre
Country [9] 0 0
Brazil
State/province [9] 0 0
Ribeirão Preto
Country [10] 0 0
Brazil
State/province [10] 0 0
Rio De Janeiro
Country [11] 0 0
Brazil
State/province [11] 0 0
São Paulo
Country [12] 0 0
Brazil
State/province [12] 0 0
Vitória
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
B.C.
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Canada
State/province [18] 0 0
Saskatchewan
Country [19] 0 0
Finland
State/province [19] 0 0
Helsinki
Country [20] 0 0
Ireland
State/province [20] 0 0
Leinster
Country [21] 0 0
New Zealand
State/province [21] 0 0
Christchurch
Country [22] 0 0
Singapore
State/province [22] 0 0
Singapore
Country [23] 0 0
Spain
State/province [23] 0 0
A Coruña
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Spain
State/province [25] 0 0
Girona
Country [26] 0 0
Spain
State/province [26] 0 0
Valladolid
Country [27] 0 0
United Kingdom
State/province [27] 0 0
England
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Northern Ireland
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Scotland
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Birmingham
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Cambridge
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Nottingham
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Other
Name
University of Calgary
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael D Hill, MD
Address 0 0
University of Calgary
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Overall data will be shared once the trial has been closed and data analysed. No individual participant data will be available.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Menon BK, Buck BH, Singh N, Deschaintre Y, Almekhl... [More Details]


Results not provided in https://clinicaltrials.gov/study/NCT02398656