NCT03889249

Brief 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 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,600

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Dec 2019

Typical duration for phase_3

Geographic Reach
1 country

22 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 20, 2019

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 26, 2019

Completed
9 months until next milestone

Study Start

First participant enrolled

December 10, 2019

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 26, 2022

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2023

Completed
Last Updated

May 12, 2023

Status Verified

May 1, 2023

Enrollment Period

2.4 years

First QC Date

March 20, 2019

Last Update Submit

May 11, 2023

Conditions

Stroke, AcuteThromboses, Intracranial

Outcome Measures

Primary Outcomes (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

    By telephone Follow-up between 90-120 days

Secondary Outcomes (9)

  • Discharge Destination

    90-120 days after randomization

  • Home Time

    90-120 days after randomization

  • Door to needle time

    Baseline-Day 1

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

    Baseline - Day 1

  • Recanalization

    Baseline- After Randomization- Day 1-

  • +4 more secondary outcomes

Other Outcomes (2)

  • Death within 90 days

    From Baseline- (Randomization) until Day 90

  • Number of Patients Diagnosed with a Symptomatic ICH post-acute stroke treatment by CT/MRI

    24 hours days from Baseline- (Randomization)

Study Arms (2)

Tenecteplase (tNK-TPA)

ACTIVE COMPARATOR

The 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.

Drug: Tenecteplase

Alteplase ( tPA)

ACTIVE COMPARATOR

The 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).

Drug: Alteplase

Interventions

TenecteplaseDRUG

Stroke Thrombolytic

Also known as: tNK
Tenecteplase (tNK-TPA)
AlteplaseDRUG

Stroke Thrombolytic

Also known as: tPA
Alteplase ( tPA)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • All patients with acute ischemic stroke eligible to receive intravenous alteplase as per standard care will be eligible for enrolment in the proposed trial.
  • Patients eligible for endovascular thrombectomy in addition to intravenous thrombolysis are eligible for enrolment.

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

University of Calgary

Calgary, Alberta, T2N2T9, Canada

Location

Grey Nuns Hospital

Edmonton, Alberta, Canada

Location

University of Alberta

Edmonton, Alberta, Canada

Location

Medicine Hat Regional Hospital

Medicine Hat, Alberta, Canada

Location

Red Deer Regional Hospital

Red Deer, Alberta, Canada

Location

Kelowna General Hospital

Kelowna, B.C., Canada

Location

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

University of Manitoba

Winnipeg, Manitoba, Canada

Location

Halifax Infirmary Queen Elizabeth II

Halifax, Nova Scotia, Canada

Location

Hamilton Health Sciences General Hospital

Hamilton, Ontario, Canada

Location

Kingston Health Science Centre

Kingston, Ontario, Canada

Location

London Health Sciences

London, Ontario, Canada

Location

Ottawa Civic Hospital

Ottawa, Ontario, Canada

Location

St. Michaels Hospital

Toronto, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Toronto Western Hospital

Toronto, Ontario, Canada

Location

Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada

Location

CHUM -Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada

Location

Univerisite Laval-Hopital de l'Enfant-Jesus

Québec, Quebec, Canada

Location

Universite de Sherbrooke

Sherbrooke, Quebec, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Location

Related Publications (7)

  • 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.

    PMID: 40677228DERIVED

  • 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.

    PMID: 40123483DERIVED

  • 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.

    PMID: 39379314DERIVED

  • 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.

    PMID: 38275116DERIVED

  • 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.

    PMID: 38174568DERIVED

  • 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.

    PMID: 37800372DERIVED

  • 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.

    PMID: 35779553DERIVED

MeSH Terms

Conditions

StrokeIntracranial Thrombosis

Interventions

TenecteplaseTissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesIntracranial Embolism and ThrombosisThromboembolismEmbolism and Thrombosis

Intervention Hierarchy (Ancestors)

Serine EndopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesSerine ProteasesPlasminogen ActivatorsBlood Coagulation FactorsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsBiological Factors

Study Officials

  • Bijoy K Menon, MD

    University of Calgary

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
90 day outcomes are assessed in a blinded manner
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Stroke Neurologist, Principal Investigator

Study Record Dates

First Submitted

March 20, 2019

First Posted

March 26, 2019

Study Start

December 10, 2019

Primary Completion

April 26, 2022

Study Completion

April 30, 2023

Last Updated

May 12, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will not share

Locations

CA(22)