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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02398656
Other study ID # Version 3.3 , Mar 24,2017
Secondary ID
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date April 2015
Est. completion date April 10, 2024

Study information

Verified date March 2024
Source University of Calgary
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 1274
Est. completion date April 10, 2024
Est. primary completion date January 19, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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. 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


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Australia Royal Adelaide Hospital Adelaide South Australia
Australia Box Hill Hospital Box Hill Victoria
Australia Calvary Public Hospital Bruce Canberra Australian Capital Territory
Australia Gold Coast University Hospital Gold Coast Queensland
Australia Royal Melbourne Hospital Melbourne Victoria
Australia Fiona Stanley Hospital Murdoch Western Australia
Australia John Hunter Hospital Newcastle New South Wales
Austria Medical University of Vienna (Coordinating Centre) Vienna
Austria St. John's of God Hospital Vienna Vienna
Brazil Hospital de Clínicas de Botucatu Botucatu
Brazil Instituto Hospital de Base do Distrito Federal Brasília
Brazil Hospital Universitário Maria Aparecida Pedrossian Campo Grande
Brazil Hospital Celso Ramos Florianopolos Celso Ramos
Brazil Hospital Geral de Fortaleza Fortaleza
Brazil Clinica Neurologica e Neurocirurgica de Joinville Ltda Joinville
Brazil Porto Alegre Hospital Porto Alegre
Brazil Santa Casa de Porto Alegre Porto Alegre
Brazil Hospital de Clínicas de Ribeirão Preto Ribeirão Preto
Brazil Americas Medical City Rio De Janeiro
Brazil Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo São Paulo
Brazil Hospital São Paulo UNIFESP São Paulo
Brazil Irmandade Da Santa Casa de Misericordia de Sao Paulo São Paulo
Brazil Hospital Estadual Central Vitória
Canada University of Calgary/Foothills Medical Centre Calgary Alberta
Canada University of Alberta Edmonton Alberta
Canada Hamilton Health Sciences Centre Hamilton Ontario
Canada Kingston General Hospital Kingston Ontario
Canada London Health Sciences Centre London Ontario
Canada McGill University Montreal Quebec
Canada Royal Columbian Hospital New Westminster B.C.
Canada Ottawa General Hospital Ottawa Ontario
Canada CHU de Québec-Université Laval Quebec City Quebec
Canada University of Saskatchewan/ Royal University Hospital Saskatoon Saskatchewan
Canada St. Michael's Hospital Toronto Ontario
Canada Sunnybrook Health Sciences Centre Toronto Ontario
Canada Toronto Western Toronto Ontario
Canada Vancouver General Hospital Vancouver British Columbia
Canada Victoria General Hospital Victoria British Columbia
Finland University Central Hospital HUCH Helsinki
Ireland Beaumont Hospital Dublin Leinster
Ireland Mater Misericordiae University Hospital Dublin Dublin Leinster
New Zealand Christchurch Hospital Christchurch
Singapore National Neuroscience Institute Tan Tock Seng Hospital Singapore
Singapore Singapore General Hospital Singapore
Spain Complejo Jospitalario Universitario A Coruna A Coruña
Spain Vall d'Hebron Institut de Recerca Barcelona
Spain Vall d'Hebron Institut de Recerca (VHIR) Barcelona
Spain Hospital Universitari Doctor Josep Trueta Girona
Spain Clinc University Hospital Valladolid Valladolid
United Kingdom Royal Victoria Hospital Belfast Northern Ireland
United Kingdom Queen Elizabeth Hospital Birmingham
United Kingdom Addenbrooke Hospital Cambridge
United Kingdom Queen Elizabeth University Hospital Glasgow Scotland
United Kingdom Charring Cross Hospital London
United Kingdom Countess of Chester London England
United Kingdom Kings College Hospital London
United Kingdom St George's University Hospitals NHS Foundation trust London England
United Kingdom Stoke University of North Midlands London England
United Kingdom University College London Hospital London England
United Kingdom Nottingham University Hospital Nottingham
United Kingdom John Radcliffe Hospital Oxford

Sponsors (1)

Lead Sponsor Collaborator
University of Calgary

Countries where clinical trial is conducted

Australia,  Austria,  Brazil,  Canada,  Finland,  Ireland,  New Zealand,  Singapore,  Spain,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Complete or partial recanalization Recanalization will be assessed by the central core-imaging lab blinded to all clinical information- TICI2b-3. 4-8 hours post treatment
Other Lawton Instrumental Activities of Daily Living Scale (IADL) This scale will be used at the Day 90 follow-up visit. 90 Days
Other Quality of life measured on EuroQol38 This scale will be used at the Day 90 follow-up visit. 90 Days
Primary 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.
90 Days
Secondary 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. 90 Days
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