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Stroke, AcutePhase 3AcTNCT03889249

Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke

A Phase 3 study testing Tenecteplase and Alteplase in people with Stroke, Acute and Thromboses, Intracranial, run by University of Calgary at 22 sites in Canada.

Completed

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

Official record
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Trial summary

The proposed trial is a pragmatic, registry linked, prospective, randomized (1:1) controlled, open-label parallel group clinical trial with blinded endpoint assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non-inferior to intravenous alteplase (0.9 mg/kg body… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stroke, Acute, Thromboses, Intracranial
What is being tested?
Tenecteplase and Alteplase
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,600 participants
Where
22 sitesCanada
Study dates
10 Dec 2019to 30 Apr 2023
Phase
Phase 3
Are there results?
None posted in the registry

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

None listed.

Who cannot join

  • Contra-indications to intravenous thrombolysis as used by treating physicians as current standard of care apply.
  • The benefits of thrombolysis with intravenous alteplase in the pediatric population is unknown. Any patient < 18 years of age may therefore not be enrolled.
  • Women with pregnancy known to the investigator by history or examination, without requiring pregnancy testing, may only be enrolled in consultation with an expert stroke physician (either in person or through tele-stroke)

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

Canada22 sites

  • University of Calgary

    Calgary, Alberta, T2N2T9

  • Queen Elizabeth Hospital

    Charlottetown, Prince Edward Island

  • Grey Nuns Hospital

    Edmonton, Alberta

  • University of Alberta

    Edmonton, Alberta

  • Halifax Infirmary Queen Elizabeth II

    Halifax, Nova Scotia

  • Hamilton Health Sciences General Hospital

    Hamilton, Ontario

  • Kelowna General Hospital

    Kelowna, B.C.

  • Kingston Health Science Centre

    Kingston, Ontario

  • London Health Sciences

    London, Ontario

  • Medicine Hat Regional Hospital

    Medicine Hat, Alberta

  • CHUM -Centre Hospitalier de l'Universite de Montreal

    Montreal, Quebec

  • Royal Columbian Hospital

    New Westminster, British Columbia

  • Ottawa Civic Hospital

    Ottawa, Ontario

  • Univerisite Laval-Hopital de l'Enfant-Jesus

    Québec, Quebec

  • Red Deer Regional Hospital

    Red Deer, Alberta

  • Royal University Hospital

    Saskatoon, Saskatchewan

  • Universite de Sherbrooke

    Sherbrooke, Quebec

  • St. Michaels Hospital

    Toronto, Ontario

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario

  • Toronto Western Hospital

    Toronto, Ontario

  • Vancouver General Hospital

    Vancouver, British Columbia

  • University of Manitoba

    Winnipeg, Manitoba

Other trials in Canada

About this study

Official title: Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke: QuICR & OPTIMISE Registry Based Pragmatic Randomized Controlled Trial

The proposed trial is a pragmatic, registry linked, prospective, randomized (1:1) controlled, open-label parallel group clinical trial with blinded endpoint assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non-inferior to intravenous alteplase (0.9 mg/kg body weight) in patients with acute ischemic stroke otherwise eligible for intravenous thrombolysis as per standard care. All patients will have standard of care medical management on an acute stroke unit. There are no additional trial specific management recommendations. Patients will be followed for approximately 90-120 days.

Read the detailed description

There are two established therapies for acute ischemic stroke, namely intravenous alteplase and endovascular thrombectomy (EVT). The guiding principles behind these therapies are fast, effective and safe reperfusion of ischemic brain. Patients with acute ischemic stroke presenting within 4.5 hours from symptom onset are administered intravenous alteplase. If there is evidence of large vessel occlusion (LVO), these patients are transferred to the nearest comprehensive stroke center (CSC) for EVT.Physicians, hospitals and health systems are focused on implementing efficient triaging systems and workflow processes to improve speed and efficacy of administration of these life-saving therapies. Although efforts over the years with intravenous alteplase administration has resulted in improvement in efficiency metrics like door to needle time (DTN) and door-in-door-out (DIDO) time, these metrics are still not optimal, and the therapy is underutilized. Physicians continue to have concerns about low early reperfusion rates, increased risk of symptomatic intracerebral hemorrhage and challenges with drug administration (bolus + 60-minute infusion) with intravenous alteplase.

Recent phase II trials have shown that intravenous tenecteplase is potentially safer and may achieve higher early reperfusion rates than alteplase in patients with acute ischemic stroke. Bolus administration makes tenecteplase easier to administer than alteplase (which requires infusion pumps). Transfer of patients from primary stroke centers (PSC) to comprehensive stroke centers (CSCs) is potentially easier without infusion pumps. Moreover, depending on the province, tenecteplase either costs the same, or even less, than alteplase. It is therefore possible that the use of intravenous tenecteplase in patients with acute ischemic stroke otherwise eligible for intravenous alteplase may result in faster administration of thrombolysis and more efficient transport to CSCs, thus saving time, reducing adverse events (intracranial hemorrhage) and potentially improving patient outcomes, while saving the health system costs. For these various reasons, robust evidence that tenecteplase is non-inferior to alteplase as an intravenous thrombolytic agent in patients with acute ischemic stroke will change current clinical practice as it did in patients with myocardial infarction. The proposed trial is therefore a pragmatic, registry linked, prospective, randomized (1:1) controlled, open-label parallel group clinical trial with blinded endpoint assessment of 1600 patients to generate real world evidence whether intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non-inferior to intravenous alteplase (0.9 mg/kg body weight) in patients with acute ischemic stroke otherwise eligible for intravenous thrombolysis as per current standard of care.

Being tested
Tenecteplase, Alteplase
Medical subject headings
Stroke, Intracranial Thrombosis

What participants receive

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

  • TenecteplaseDrug

    Also called tNK

    Stroke Thrombolytic

  • AlteplaseDrug

    Also called tPA

    Stroke Thrombolytic

Study groups in NCT03889249
Study groupRoleWhat they receive
Tenecteplase (tNK-TPA)Active comparatorThe intervention group will receive intravenous tenecteplase as a single bolus as per the standard manufacturers' instructions for use. The dose administered will be 0.25 mg/kg body weight (maximum dose 25 mg) over 10-20 seconds as soon as possible after randomization. Tenecteplase 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
Alteplase ( tPA)Active comparatorThe control group will receive standard of care dosing of intravenous alteplase (0.9 mg/kg body weight, 10% bolus and 90% infusion as per standard care, maximum dose 90 mg).
Receives: Drug: Alteplase

What is being measured

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

  1. Modified Rankin Scale (mRS) 0-1 (freedom from disability)

    The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS is a range from 0-6. 0=No symptoms, 1=No significant disability. Able to carry out all usual activities, despite some symptoms 2=Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.3=Moderate disability. Requires some help, but able to walk unassisted4=Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.5=Severe disability. Requires constant nursing care and attention, bedridden, incontinent.6=Dead

    Measured: By telephone Follow-up between 90-120 days

Secondary outcomes (9)

  1. Discharge Destination

    Location where the patient is living at 90-120 days from randomization. Locations include home, early supported discharge, rehabilitation facility, long term care, death.

    Measured: 90-120 days after randomization

  2. Home Time

    Defined as number of days subject spends at home after index stroke event. The home time outcome will be determined through linkage with administrative data to calculate the total time in the first 90 days after index event that a stroke patient is not an inpatient.

    Measured: 90-120 days after randomization

  3. Door to needle time

    Time from when the patient enters the Emergency Room until treatment with either tNK or tPA. Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.

    Measured: Baseline-Day 1

  4. Door-in-door-out (DIDO) times at Primary Stroke Centres

    The amount of time from when the patient enters the Emergency room to the time of discharge from the same hospital is collected. Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.

    Measured: Baseline - Day 1

  5. Recanalization

    Recanalization status (mTICI score) at first angiographic acquisition in patients taken to the angio-suite for the purpose of administering EVT.Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.

    Measured: Baseline- After Randomization- Day 1-

  6. Proportion of patients administered EVT

    Patients receiving Endovascular Therapy after being treated with either tNK or tPA.Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.

    Measured: After IV thrombolysis -within the first hour after randomization - baseline-Day 1

  7. Door-to-groin puncture time in patients undergoing EVT

    Patients receiving Endovascular Therapy after being treated with either tNK or tPA-treatment time. Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.

    Measured: During EVT administration-Baseline- after randomization

  8. CT-to-puncture time in patients undergoing EVT

    Patients receiving Endovascular Therapy after being treated with either tNK or tPA-treatment time. Secondary outcome measures described above are all available through the QuICR and OPTIMISE registries and will be collected from those data sources.

    Measured: Before EVT administration- baseline- after Randomization- Day 1

  9. % patients returning to baseline level of functioning

    Patient or surrogate reported return to baseline level of functioning

    Measured: By telephone Follow-up between 90-120 days

Timeline

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

  1. First posted26 Mar 2019
  2. Study start10 Dec 2019
  3. Primary completion26 Apr 2022
  4. Study completion30 Apr 2023

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
Model description
The proposed trial is a pragmatic, registry linked, prospective, randomized (1:1) controlled, open-label parallel group clinical trial with blinded endpoint assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non-inferior to intravenous alteplase (0.9 mg/kg body weight) in patients with acute ischemic stroke otherwise eligible for intravenous thrombolysis as per standard care.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1,600 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03889249
Sponsor's protocol ID
Version 2.0 (Sponsor assigned)
Acronym
AcT
Status last verified
May 2023
First submitted
20 Mar 2019
Last updated
12 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Arimoro OI, Ademola A, Hill MD, Menon BK, Sajobi TT. Evaluating Differential Item Functioning in EQ-5D-5L in Acute Ischemic Stroke: Evidence From the ACT Trial. Stroke. 2026 Jul 23. doi: 10.1161/STROKEAHA.126.055939. Online ahead of print.

    PubMed 42488952

  • Appoo A, Ignacio K, Doolan C, Bala F, Almekhlafi M, Buck BH, Tkach A, Catanese L, Swartz RH, Sajobi TT, Ganesh A, Menon BK, Singh N. Predictors and Consequences of Serious Adverse Events in Patients Treated With Thrombolysis: A Prespecified Secondary Analysis of the AcT Trial. J Am Heart Assoc. 2026 Jun 16;15(12):e048280. doi: 10.1161/JAHA.125.048280. Epub 2026 Jun 9.

    PubMed 42261967

  • Ignacio KHD, Bala F, Catanese L, Tkach A, Kate M, Buck B, Ademola A, Sajobi TT, Field TS, Pikula A, Shamy M, Hunter G, Swartz RH, Horn M, Dowlatshahi D, Shankar JJ, Hill MD, Menon BK, Almekhlafi MA, Singh N. Comparing Clinical Characteristics and Outcomes of Tenecteplase Versus Alteplase in Young Adult Patients With Stroke: A Secondary Analysis of the AcT Trial. Stroke Vasc Interv Neurol. 2026 Jan 22;6(2):e001974. doi: 10.1161/SVIN.125.001974. eCollection 2026 Mar.

    PubMed 41815318

  • Sujanthan S, Rajkumar G, Dainty KN, Barense M, Lanctot KL, Owen AM, Singh N, Buck BH, Khosravani H, Coutts SB, Almekhlafi M, Appireddy R, Tkach A, Catanese L, Dowlatshahi D, Mandzia J, Pikula A, Williams H, Field TS, Manosalva A, Siddiqui M, Hunter G, Horn M, Bala F, Hill MD, Shamy M, Ganesh A, Sajobi T, Menon BK, Swartz RH; AcT Trial Investigators. Faster Thrombolysis Is Associated With Improved Cognitive Outcomes in Patients With Acute Ischemic Stroke Treated With Alteplase and Tenecteplase: A Substudy of the AcT Trial. Stroke. 2025 Oct;56(10):2858-2865. doi: 10.1161/STROKEAHA.125.051670. Epub 2025 Jul 18.

    PubMed 40677228

  • Singh N, Bala F, Ademola A, Almekhlafi M, Coutts SB, Deschaintre Y, Khosravani H, Buck BH, Appireddy R, Moreau F, Gubitz G, Tkach A, Catanese L, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar JJ, Poppe AY, Williams H, Field TS, Manosalva A, Siddiqui M, Zafar A, Imoukhoude O, Hunter G, Shamy M, Demchuk A, Swartz RH, Hill MD, Sajobi TT, Menon BK, Ganesh A. Safety, Functional Disability, Healthcare Utilization, and Quality-of-Life Outcomes in Elderly Receiving Alteplase and Tenecteplase: A Secondary Analysis From the AcT Trial. Stroke. 2025 May;56(5):1169-1179. doi: 10.1161/STROKEAHA.124.049512. Epub 2025 Mar 24.

    PubMed 40123483

  • Bala F, Diprose W, Menon BK, Singh N, Khosravani H, Tkach A, Catanese L, Dowlatshahi D, Field TS, Hunter G, Sajobi T, Hill MD, Buck BH, Swartz RH, Almekhlafi MA. Effect of thrombolysis type on the efficacy of aspiration versus stent retriever first line thrombectomy: results from the AcT trial. J Neurointerv Surg. 2025 Jun 1;17(e2):e276-e280. doi: 10.1136/jnis-2024-022268.

    PubMed 39379314

  • Sajobi TT, Arimoro OI, Ademola A, Singh N, Bala F, Almekhlafi MA, Deschaintre Y, Coutts SB, Thirunavukkarasu S, Khosravani H, Appireddy R, Moreau F, Gubitz GJ, Tkach A, Catanese L, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar JS, Williams H, Field TS, Manosalva A, Siddiqui M, Zafar A, Imoukhuede O, Hunter G, Demchuk AM, Mishra SM, Gioia LC, Jalini S, Cayer C, Phillips SJ, Elamin E, Shoamanesh A, Subramaniam S, Kate MP, Jacquin G, Camden MC, Benali F, Alhabli I, Horn M, Stotts G, Hill MD, Gladstone DJ, Poppe AY, Sehgal A, Zhang Q, Lethebe B, Doram C, Shamy M, Kenney C, Buck BH, Swartz RH, Menon BK. Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial. Stroke. 2024 Mar;55(3):524-531. doi: 10.1161/STROKEAHA.123.044690. Epub 2024 Jan 26.

    PubMed 38275116

  • Kim DJ, Singh N, Catanese L, Yu AYX, Demchuk AM, Lloret-Villas MI, Deschaintre Y, Coutts SB, Khosravani H, Appireddy R, Moreau F, Gubitz G, Tkach A, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar J, Williams H, Manosalva H, Siddiqui M, Zafar A, Imoukhuede O, Hunter G, Phillips S, Hill MD, Poppe AY, Ademola A, Shamy M, Bala F, Sajobi TT, Swartz RH, Almekhlafi MA, Menon BK, Field TS. Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase. Stroke. 2024 Feb;55(2):288-295. doi: 10.1161/STROKEAHA.123.045320. Epub 2024 Jan 4.

    PubMed 38174568

  • Singh N, Almekhlafi MA, Bala F, Ademola A, Coutts SB, Deschaintre Y, Khosravani H, Buck B, Appireddy R, Moreau F, Gubitz G, Tkach A, Catanese L, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar JJ, Ghrooda E, Poppe AY, Williams H, Field TS, Manosalva A, Siddiqui MM, Zafar A, Imoukhoude O, Hunter G, Shamy M, Demchuk AM, Claggett BL, Hill MD, Sajobi TT, Swartz RH, Menon BK. Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial. Stroke. 2023 Nov;54(11):2766-2775. doi: 10.1161/STROKEAHA.123.044267. Epub 2023 Oct 6.

    PubMed 37800372

  • Menon BK, Buck BH, Singh N, Deschaintre Y, Almekhlafi MA, Coutts SB, Thirunavukkarasu S, Khosravani H, Appireddy R, Moreau F, Gubitz G, Tkach A, Catanese L, Dowlatshahi D, Medvedev G, Mandzia J, Pikula A, Shankar J, Williams H, Field TS, Manosalva A, Siddiqui M, Zafar A, Imoukhuede O, Hunter G, Demchuk AM, Mishra S, Gioia LC, Jalini S, Cayer C, Phillips S, Elamin E, Shoamanesh A, Subramaniam S, Kate M, Jacquin G, Camden MC, Benali F, Alhabli I, Bala F, Horn M, Stotts G, Hill MD, Gladstone DJ, Poppe A, Sehgal A, Zhang Q, Lethebe BC, Doram C, Ademola A, Shamy M, Kenney C, Sajobi TT, Swartz RH; AcT Trial Investigators. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022 Jul 16;400(10347):161-169. doi: 10.1016/S0140-6736(22)01054-6. Epub 2022 Jun 29.

    PubMed 35779553

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tenecteplase and Alteplase in people with Stroke, Acute and Thromboses, Intracranial, run by University of Calgary at 22 sites in Canada.

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 0 inclusion and 3 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 12 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Canada. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Modified Rankin Scale (mRS) 0-1 (freedom from disability) (time frame: By telephone Follow-up between 90-120 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 NCT03889249, which also lists 10 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 12 May 2023.

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