A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion (TEMPO-2)
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|ClinicalTrials.gov Identifier: NCT02398656|
Recruitment Status : Recruiting
First Posted : March 25, 2015
Last Update Posted : April 17, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Stroke, Acute||Drug: Tenecteplase Drug: Antiplatelet treatment||Phase 3|
TEMPO2 is an multicentre, prospective randomized open label, blinded-endpoint (PROBE) controlled trial of thrombolysis with low dose Tenecteplase (TNK-tPA) versus standard of care. A total of 1274 patients will be enrolled, at approximately 50 sites worldwide.
TEMPO-2 will enroll patients within a 12 hour time window with a NIHSS score of <6 and an ASPECTS >7. All patients will be evaluated clinically and then undergo brain imaging using CT followed immediately by a CT angiogram. Patients must have an intracranial occlusion on CTA or CTP.
Randomization will be 1:1 to TNK-tPA (experimental) or standard of care antiplatelet agents (control).
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.
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. The local investigator to chose which antithrombotic regime should be used
All patients will be treated within 90 minutes of the first slice of the baseline CT. Patients will undergo a study CT angiogram of the intracranial circulation between 4-8 hours after treatment to determine whether the occluded artery has recanalized or not. In sites where MRI/MRA is routinely used this can be substituted for CT/CTA. Any patient who has neurological worsening should have standard of care brain imaging completed to rule out intracranial hemorrhage.
All patients will have standard of care medical management on an acute stroke unit and undergo follow-up imaging at 24 hours with CT or MR. Use of MR will be encouraged.
Patients will be assessed at 24 hours and at Days 5 and 90. The Day 90 Outcomes will be performed by a blinded assessor.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1274 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official 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|
|Study Start Date :||April 2015|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2023|
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.
TNK will be administered as a single intravenous bolus over 1-2 minutes within 90 minutes of the CT scan.
Other Name: TNK-tPA
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.
Drug: 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.
Other Name: ASA, Clopidogrel
- Modified Rankin Scale (mRS) [ Time Frame: 90 Days ]
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.
- Major Bleeding [ Time Frame: 90 Days ]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.
- Complete or partial recanalization [ Time Frame: 4-8 hours post treatment ]Recanalization will be assessed by the central core-imaging lab blinded to all clinical information- TICI2b-3.
- Lawton Instrumental Activities of Daily Living Scale (IADL) [ Time Frame: 90 Days ]This scale will be used at the Day 90 follow-up visit.
- Quality of life measured on EuroQol38 [ Time Frame: 90 Days ]This scale will be used at the Day 90 follow-up visit.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02398656
|Contact: Shelagh B Coutts, MDemail@example.com|
|Contact: Carol C Kenney, RN, CCRPfirstname.lastname@example.org|
|Study Director:||Michael D Hill, MD||University of Calgary|