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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02398656
Ethics application status
Date submitted
20/03/2015
Date registered
25/03/2015
Date last updated
17/04/2019

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) - Analysis will be a responder analysis where return to baseline level of neurological functioning is defined as follows:
If pre-morbid mRS is 0-1 then mRS 0-1 at 90 days is a good outcome. If pre-morbid mRS is 2 then mRS 0-2 is a good outcome.
Pre-morbid mRS is assessed using the structured mRS prior to randomization. Outcomes will be assessed by an individual blinded to the treatment assignment. The 90day mRS will be rated using the structured mRS questionnaire . The 90 day mRS will be completed in person where possible and by telephone otherwise. The structured questionnaire has been showed to improve reliability in assessing the mRS both in person and by telephone.
Timepoint [1] 0 0
90 Days
Secondary outcome [1] 0 0
Major Bleeding - 1) Proportion of patients with major bleeding: This will include an analysis of symptomatic intracranial hemorrhage alone and then combined with major extracranial hemorrhage. This is the main safety outcome.
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
Gender
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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] 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 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 outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Vienna
Country [2] 0 0
Canada
State/province [2] 0 0
Alberta
Country [3] 0 0
Canada
State/province [3] 0 0
British Columbia
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Canada
State/province [5] 0 0
Quebec
Country [6] 0 0
Canada
State/province [6] 0 0
Saskatchewan
Country [7] 0 0
Ireland
State/province [7] 0 0
Leinster
Country [8] 0 0
Singapore
State/province [8] 0 0
Singapore
Country [9] 0 0
Spain
State/province [9] 0 0
A Coruña
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona
Country [11] 0 0
Spain
State/province [11] 0 0
Valladolid
Country [12] 0 0
United Kingdom
State/province [12] 0 0
England
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Scotland

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

Ethics approval
Ethics application status

Summary
Brief summary
This trial will enroll patients that have been diagnosed with a transient ischemic attack
(TIA) or minor stroke that has occurred within the past 12 hours. Anyone diagnosed with a
minor stroke faces the possibility of long-term disability and even death, regardless of
treatment. Stroke symptoms such as weakness, difficulty speaking and paralysis may improve or
worsen over the hours or days immediately following a stroke. TEMPO-2 is a minor stroke trial
for patients presenting within 12 hours of their symptom onset. Patients will be randomized
to TNK-tPA or standard of care. In the intervention group TNK-tPA is given as a single,
intravenous bolus (0.25mg/Kg) immediately upon randomization. Maximum dose 50mg. The control
group will receive antiplatelet agent(s) as decided by the treating physician. Antiplatelet
agent(s) choice will be at the treating physician's discretion.

TEMPO-2 Coordinating Centre is located in Calgary, AB, Canada. There will be approximately 50
sites participating worldwide.

Dr. Shelagh Coutts is the Principal Investigator.
Trial website
https://clinicaltrials.gov/show/NCT02398656
Trial related presentations / publications
Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, Subramaniam S, Goyal M, Patil S, Menon BK, Barber PA, Dowlatshahi D, Field T, Asdaghi N, Camden MC, Hill MD; TEMPO-1 Investigators. Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015 Mar;46(3):769-74. doi: 10.1161/STROKEAHA.114.008504. Epub 2015 Feb 12.
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
Shelagh B Coutts, MD
Address 0 0
Country 0 0
Phone 0 0
403-944-1581
Fax 0 0
Email 0 0
scoutts@ucalgary.ca
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02398656