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Stroke, AcutePhase 3TEMPO-2NCT02398656

A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion

A Phase 3 study testing Tenecteplase and Antiplatelet treatment in people with Stroke, Acute, run by University of Calgary at 61 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stroke, Acute
What is being tested?
Tenecteplase and Antiplatelet treatment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,274 participants
Where
61 sitesin 10 countries
Study dates
1 Apr 2015to 10 Apr 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Acute ischemic stroke in an adult patient (18 years of age or older)
  • Onset (last-seen-well) time to treatment time ≤ 12 hours.
  • 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.
  • 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.
  • Pre-stroke independent functional status - structured mRS ≤2.
  • Informed consent from the patient or surrogate.
  • 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.

Who cannot join

  • Hyperdensity on NCCT consistent with intracranial hemorrhage.
  • Large acute stroke ASPECTS < 7 visible on baseline CT scan.
  • 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.
  • Clinical history, past imaging or clinical judgment suggest that that intracranial occlusion is chronic.
  • 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.
  • Pregnancy
Show all 18Show fewer
  • Planned thrombolysis with IV tPA or endovascular thrombolysis/thrombectomy treatment.
  • 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.
  • 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.

Trial locations and contacts

61 sites in 10 countries.

61 sites in 10 countries

Canada15 sites

  • University of Calgary/Foothills Medical Centre

    Calgary, Alberta, T2N 2T9

  • University of Alberta

    Edmonton, Alberta

  • Hamilton Health Sciences Centre

    Hamilton, Ontario

  • Kingston General Hospital

    Kingston, Ontario

  • London Health Sciences Centre

    London, Ontario

  • McGill University

    Montreal, Quebec

  • Royal Columbian Hospital

    New Westminster, B.C., V3L 3W7

  • Ottawa General Hospital

    Ottawa, Ontario

  • CHU de Québec-Université Laval

    Québec, Quebec

  • University of Saskatchewan/ Royal University Hospital

    Saskatoon, Saskatchewan

  • St. Michael's Hospital

    Toronto, Ontario

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario

  • Toronto Western

    Toronto, Ontario

  • Vancouver General Hospital

    Vancouver, British Columbia

  • Victoria General Hospital

    Victoria, British Columbia

Other trials in Canada

Brazil14 sites

  • Hospital de Clínicas de Botucatu

    Botucatu

  • Instituto Hospital de Base do Distrito Federal

    Brasília

  • Hospital Universitário Maria Aparecida Pedrossian

    Campo Grande

  • Hospital Celso Ramos Florianopolos

    Celso Ramos

  • Hospital Geral de Fortaleza

    Fortaleza

  • Clinica Neurologica e Neurocirurgica de Joinville Ltda

    Joinville

  • Porto Alegre Hospital

    Porto Alegre

  • Santa Casa de Porto Alegre

    Porto Alegre

  • Hospital de Clínicas de Ribeirão Preto

    Ribeirão Preto

  • Americas Medical City

    Rio de Janeiro

  • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

    São Paulo

  • Hospital São Paulo UNIFESP

    São Paulo

  • Irmandade Da Santa Casa de Misericordia de Sao Paulo

    São Paulo

  • Hospital Estadual Central

    Vitória

Other trials in Brazil

United Kingdom12 sites

  • Royal Victoria Hospital

    Belfast, Northern Ireland

  • Queen Elizabeth Hospital

    Birmingham

  • Addenbrooke Hospital

    Cambridge

  • Queen Elizabeth University Hospital

    Glasgow, Scotland

  • Countess of Chester

    London, England

  • St George's University Hospitals NHS Foundation trust

    London, England

  • Stoke University of North Midlands

    London, England

  • University College London Hospital

    London, England

  • Charring Cross Hospital

    London

  • Kings College Hospital

    London

  • Nottingham University Hospital

    Nottingham

  • John Radcliffe Hospital

    Oxford

Other trials in United Kingdom

Australia7 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia

  • Box Hill Hospital

    Box Hill, Victoria

  • Calvary Public Hospital Bruce

    Canberra, Australian Capital Territory

  • Gold Coast University Hospital

    Gold Coast, Queensland

  • Royal Melbourne Hospital

    Melbourne, Victoria

  • Fiona Stanley Hospital

    Murdoch, Western Australia

  • John Hunter Hospital

    Newcastle, New South Wales

Other trials in Australia

Spain5 sites

  • Complejo Jospitalario Universitario A Coruna

    A Coruña

  • Vall d'Hebron Institut de Recerca (VHIR)

    Barcelona

  • Vall d'Hebron Institut de Recerca

    Barcelona

  • Hospital Universitari Doctor Josep Trueta

    Girona

  • Clinc University Hospital Valladolid

    Valladolid

Other trials in Spain

Austria2 sites

  • Medical University of Vienna (Coordinating Centre)

    Vienna

  • St. John's of God Hospital Vienna

    Vienna

Other trials in Austria

Ireland2 sites

  • Beaumont Hospital

    Dublin, Leinster

  • Mater Misericordiae University Hospital Dublin

    Dublin, Leinster

Other trials in Ireland

Singapore2 sites

  • National Neuroscience Institute Tan Tock Seng Hospital

    Singapore

  • Singapore General Hospital

    Singapore

Other trials in Singapore

Finland1 site

  • University Central Hospital HUCH

    Helsinki

Other trials in Finland

New Zealand1 site

  • Christchurch Hospital

    Christchurch

Other trials in New Zealand

About this study

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

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.

Read the detailed 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.

Conditions
Stroke, Acute
Being tested
Tenecteplase, Antiplatelet treatment
Keywords
Minor Ischemic Stroke
Medical subject headings
Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TenecteplaseDrug

    Also called TNK-tPA

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

  • Antiplatelet treatmentDrug

    Also called ASA, Clopidogrel

    Low dose aspirin (single agent) will be the choice of most physicians, some Investigators will chose to use the combination of aspirin and clopidogrel.

Study groups in NCT02398656
Study groupRoleWhat they receive
Tenecteplase (tNK)ExperimentalExperimental: 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.
Receives: Drug: Tenecteplase
Control (Antiplatelet Agents)Active comparatorControl: 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.
Receives: Drug: Antiplatelet treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Return to Baseline Neurological Functioning Measured by the 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 at 90 days 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. This is a scale from 0-6. Higher scores mean a worse outcome.

    Measured: 90 Days

Secondary outcomes (1)

  1. Number of Participants With Modified Rankin Score (mRS) 0-1 at 90 Days

    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. This is a scale from 0-6. Higher scores mean a worse outcome.

    mRS 0-1 represents excellent functional outcome.

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2015 (estimated)
  2. Study start1 Apr 2015
  3. Primary completion19 Jan 2024
  4. Study completion10 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1,274 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02398656
Sponsor's protocol ID
Version 3.3 , Mar 24,2017
Acronym
TEMPO-2
Status last verified
Jan 2025
First submitted
20 Mar 2015
Last updated
31 Jan 2025
Data monitoring committee
Yes
Individual data sharing
No: Overall data will be shared once the trial has been closed and data analysed. No individual participant data will be available.

Publications

  • Coutts SB, Ankolekar S, Appireddy R, Arenillas JF, Assis Z, Bailey P, Barber PA, Bazan R, Buck BH, Butcher KS, Camden MC, Campbell BCV, Casaubon LK, Catanese L, Chatterjee K, Choi PMC, Clarke B, Dowlatshahi D, Ferrari J, Field TS, Ganesh A, Ghia D, Goyal M, Greisenegger S, Halse O, Horn M, Hunter G, Imoukhuede O, Kelly PJ, Kennedy J, Kenney C, Kleinig TJ, Krishnan K, Lima F, Mandzia JL, Marko M, Martins SO, Medvedev G, Menon BK, Mishra SM, Molina C, Moussaddy A, Muir KW, Parsons MW, Penn AMW, Pille A, Pontes-Neto OM, Roffe C, Serena J, Simister R, Singh N, Spratt N, Strbian D, Tham CH, Wiggam MI, Williams DJ, Willmot MR, Wu T, Yu AYX, Zachariah G, Zafar A, Zerna C, Hill MD; TEMPO-2 investigators. Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial. Lancet. 2024 Jun 15;403(10444):2597-2605. doi: 10.1016/S0140-6736(24)00921-8. Epub 2024 May 17.

    PubMed 38768626

  • Raty S, Strbian D, Singh N, Vatanpour S, Tomppo L, Ganesh A, Campbell BCV, Parsons MW, Hill MD, Coutts SB; TEMPO-2 investigators. Tenecteplase versus standard care for minor ischaemic stroke according to the baseline occlusion status in TEMPO-2 trial. Eur Stroke J. 2026 Sep 5;11(9):aakag111. doi: 10.1093/esj/aakag111.

    PubMed 42734928

  • Singh N, Strbian D, Vatanpour S, Field TS, Yu AYX, Ganesh A, Barber PA, Choi PMC, Buck BH, Kleinig TJ, Campbell B, Molina C, Muir KW, Hill MD, Coutts SB. Association of Successful Recanalization and Functional Outcomes in Minor Ischemic Stroke With Proven Occlusion: A Secondary Analysis of TEMPO-2 Trial. Stroke. 2026 Aug;57(8):2305-2314. doi: 10.1161/STROKEAHA.125.052872. Epub 2026 Jun 19.

    PubMed 42318629

  • Ganesh A, Vatanpour S, Yu AYX, Barber P, Choi PMC, Field TS, Kate MP, Kleinig TJ, Shamy MCF, Chatterjee K, Molina CA, Campbell BCV, Appireddy R, Muir KW, Hill MD, Coutts SB; as the TEMPO-2 investigators. Outcomes After Minor Ischemic Stroke in Older Patients Treated With IV Thrombolysis vs Standard of Care in the TEMPO-2 Trial. Neurology. 2026 May 12;106(9):e214925. doi: 10.1212/WNL.0000000000214925. Epub 2026 Apr 14.

    PubMed 41980227

  • Zhang Y, Buck BH, Barber PA, Chatterjee K, Clarke B, Choi PMC, Hunter G, Ganesh A, Mishra SM, Williams D, Campbell BCV, Dowlatshahi D, Butcher KS, Krishnan K, Wiggam MI, Kleinig TJ, Muir KW, Zerna C, Field TS, Goyal M, Yu AYX, Roffe C, Demchuck AM, Parsons MW, Bazan R, Ankolekar S, Kennedy J, Menon BK, Mandzia JL, Pille A, Kelly PJ, Marko M, Singh N, Vatanpour S, Lima FO, Catanese L, Horn M, Ghia D, Ferrari J, Greisenegger S, Hill MD, Coutts SB; TEMPO-2 Investigators. Thrombolysis With Tenecteplase for Minor Disabling Stroke: Secondary Analysis of the TEMPO-2 Randomized Clinical Trial. JAMA Neurol. 2025 Dec 1;82(12):1243-1250. doi: 10.1001/jamaneurol.2025.4152.

    PubMed 41143808

  • Singh N, Kenney CC, Butcher KS, Buck B, Barber PA, Field TS, Choi PM, Yu AY, Kleinig T, Appireddy R, Molina CA, Muir KW, Hill MD, Coutts SB. A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke with Proven Occlusion (TEMPO-2): Rational and design of a multicenter, randomized open-label clinical trial. Int J Stroke. 2024 Aug;19(7):817-822. doi: 10.1177/17474930241253702. Epub 2024 May 17.

    PubMed 38676572

  • Logallo N, Kvistad CE, Thomassen L. Therapeutic Potential of Tenecteplase in the Management of Acute Ischemic Stroke. CNS Drugs. 2015;29(10):811-8. doi: 10.1007/s40263-015-0280-9.

    PubMed 26387127

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tenecteplase and Antiplatelet treatment in people with Stroke, Acute, run by University of Calgary at 61 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 61 sites in Canada, Brazil, United Kingdom, Australia, Spain and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Return to Baseline Neurological Functioning Measured by the Modified Rankin Scale (mRS) (time frame: 90 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02398656, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2025.

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