NCT02388061

Brief Summary

Patients presenting to the emergency department with acute ischemic stroke, who are are eligible for standard intravenous tPA therapy within 4.5 hours of stroke onset will be assessed for major vessel occlusion to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomised 50:50 using central computerised allocation to intravenous alteplase or tenecteplase before all participants undergo intra-arterial clot retrieval. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
202

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Mar 2015

Typical duration for phase_2

Geographic Reach
2 countries

18 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 9, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 13, 2015

Completed
10 days until next milestone

Study Start

First participant enrolled

March 23, 2015

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 16, 2017

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2018

Completed
Last Updated

March 30, 2018

Status Verified

March 1, 2018

Enrollment Period

2.6 years

First QC Date

March 9, 2015

Last Update Submit

March 28, 2018

Conditions

Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

  • Proportion of patients with substantial angiographic reperfusion (mTICI) score of 2b/3 (restoration of blood flow to >50% of the affected arterial territory) or absence of retrievable thrombus at initial angiogram.

    Initial angiogram (day 0)

Secondary Outcomes (7)

  • Proportion of patients with ≥8 point reduction in NIHSS or reaching 0-1 at 3 days (favourable clinical response) adjusted for baseline NIHSS and age.

    Initial angiogram (day 0)

  • Modified Rankin Scale (mRS) at 3 months

    3 months post stroke

  • mRS 0-1 or no change from baseline at 3 months

    3 months post stroke

  • mRS 0-2 or no change from baseline at 3 months

    3 months post stroke

  • Symptomatic intracranial hemorrhage (SICH)

    within 36 hours post treatment

  • +2 more secondary outcomes

Study Arms (2)

Intravenous tenecteplase (TNK)

EXPERIMENTAL

Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over \~10 seconds).

Drug: Tenecteplase

Intravenous tissue plasminogen activator (tPA)

ACTIVE COMPARATOR

Patients will receive intravenous t-PA at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.

Drug: Tissue Plasminogen Activator

Interventions

TenecteplaseDRUG
Also known as: TNK
Intravenous tenecteplase (TNK)
Tissue Plasminogen ActivatorDRUG
Also known as: Alteplase, tPA
Intravenous tissue plasminogen activator (tPA)

Eligibility Criteria

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

You may qualify if:

  • Patients presenting with acute ischemic stroke eligible using standard criteria to receive IV thrombolysis within 4.5 hours of stroke onset
  • Patient's age is ≥18 years
  • Intra-arterial clot retrieval treatment can commence (arterial puncture) within 6 hours of stroke onset.
  • Arterial occlusion on CTA or MRA of the ICA, M1, M2 or basilar artery.

You may not qualify if:

  • Intracranial hemorrhage (ICH) identified by CT or MRI
  • Rapidly improving symptoms at the discretion of the investigator
  • Pre-stroke mRS score of ≥ 4 (indicating previous disability)
  • Hypodensity in \>1/3 MCA territory or equivalent proportion of basilar artery territory on non-contrast CT
  • Contra indication to imaging with contrast agents
  • Any terminal illness such that patient would not be expected to survive more than 1 year
  • Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
  • Pregnant women

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

John Hunter Hospital

Newcastle, New South Wales, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Brisbane & Women's Hospital

Brisbane, Queensland, Australia

Location

Gold Coast University Hospital

Gold Coast, Queensland, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Austin Hospital

Heidelberg, Victoria, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Western Heath

St Albans, Victoria, 3021, Australia

Location

Auckland Hospital

Grafton, Auckland, 1001, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Related Publications (9)

  • Yogendrakumar V, Beharry J, Churilov L, Pesavento L, Alidin K, Ugalde M, Weir L, Mitchell PJ, Kleinig TJ, Yassi N, Thijs VN, Wu TY, Brown H, Dewey HM, Wijeratne T, Yan B, Sharma GJ, Desmond P, Parsons MW, Donnan GA, Davis SM, Campbell BCV; EXTEND-IA TNK and Royal Melbourne Stroke Registry Investigators. Association of Time to Thrombolysis With Early Reperfusion After Alteplase and Tenecteplase in Patients With Large Vessel Occlusion. Neurology. 2024 Apr 9;102(7):e209166. doi: 10.1212/WNL.0000000000209166. Epub 2024 Mar 19.

    PMID: 38502892DERIVED

  • Yogendrakumar V, Churilov L, Mitchell PJ, Kleinig TJ, Yassi N, Thijs V, Wu T, Shah D, Bailey P, Dewey HM, Choi PMC, Ma A, Wijeratne T, Garcia-Esperon C, Cloud G, Chandra RV, Cordato DJ, Yan B, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM, Campbell BCV; EXTEND-IA TNK Investigators. Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials. Neurology. 2023 May 2;100(18):e1900-e1911. doi: 10.1212/WNL.0000000000207138. Epub 2023 Mar 6.

    PMID: 36878701DERIVED

  • Sarraj A, Albers GW, Mitchell PJ, Hassan AE, Abraham MG, Blackburn S, Sharma G, Yassi N, Kleinig TJ, Shah DG, Wu TY, Hussain MS, Tekle WG, Gutierrez SO, Aghaebrahim AN, Haussen DC, Toth G, Pujara D, Budzik RF, Hicks W, Vora N, Edgell RC, Slavin S, Lechtenberg CG, Maali L, Qureshi A, Rosterman L, Abdulrazzak MA, AlMaghrabi T, Shaker F, Mir O, Arora A, Martin-Schild S, Sitton CW, Churilov L, Gupta R, Lansberg MG, Nogueira RG, Grotta JC, Donnan GA, Davis SM, Campbell BCV; SELECT, EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK Part-II Investigators. Thrombectomy Outcomes With General vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study. Neurology. 2023 Jan 17;100(3):e336-e347. doi: 10.1212/WNL.0000000000201384. Epub 2022 Oct 26.

    PMID: 36289001DERIVED

  • Yogendrakumar V, Churilov L, Mitchell PJ, Kleinig TJ, Yassi N, Thijs V, Wu TY, Shah DG, Ng FC, Dewey HM, Wijeratne T, Yan B, Desmond PM, Parsons MW, Donnan GA, Davis SM, Campbell BCV; EXTEND-IA TNK Investigators. Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion: A Pooled Analysis of the EXTEND-IA TNK Trials. Neurology. 2022 Mar 22;98(12):e1292-e1301. doi: 10.1212/WNL.0000000000013302. Epub 2022 Jan 11.

    PMID: 35017305DERIVED

  • Ng FC, Churilov L, Yassi N, Kleinig TJ, Thijs V, Wu T, Shah D, Dewey H, Sharma G, Desmond P, Yan B, Parsons M, Donnan G, Davis S, Mitchell P, Campbell B. Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow). Neurology. 2022 Feb 22;98(8):e790-e801. doi: 10.1212/WNL.0000000000013210. Epub 2021 Dec 14.

    PMID: 34906976DERIVED

  • Alemseged F, Ng FC, Williams C, Puetz V, Boulouis G, Kleinig TJ, Rocco A, Wu TY, Shah D, Arba F, Kaiser D, Di Giuliano F, Morotti A, Sallustio F, Dewey HM, Bailey P, O'Brien B, Sharma G, Bush S, Dowling R, Diomedi M, Churilov L, Yan B, Parsons MW, Davis SM, Mitchell PJ, Yassi N, Campbell BCV; BATMAN study group and EXTEND IA TNK study group. Tenecteplase vs Alteplase Before Endovascular Therapy in Basilar Artery Occlusion. Neurology. 2021 Mar 2;96(9):e1272-e1277. doi: 10.1212/WNL.0000000000011520. Epub 2021 Jan 6.

    PMID: 33408145DERIVED

  • Gao L, Moodie M, Mitchell PJ, Churilov L, Kleinig TJ, Yassi N, Yan B, Parsons MW, Donnan GA, Davis SM, Campbell BCV; EXTEND-IA TNK Investigators. Cost-Effectiveness of Tenecteplase Before Thrombectomy for Ischemic Stroke. Stroke. 2020 Dec;51(12):3681-3689. doi: 10.1161/STROKEAHA.120.029666. Epub 2020 Oct 7.

    PMID: 33023423DERIVED

  • Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Investigators. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582. doi: 10.1056/NEJMoa1716405.

    PMID: 29694815DERIVED

  • Campbell BC, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Yan B, Dowling RJ, Bush SJ, Dewey HM, Thijs V, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi C, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bailey P, Rice H, de Villiers L, Scroop R, Collecutt W, Wong AA, Coulthard A, Barber PA, McGuinness B, Field D, Ma H, Chong W, Chandra RV, Bladin CF, Brown H, Redmond K, Leggett D, Cloud G, Madan A, Mahant N, O'Brien B, Worthington J, Parker G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Investigators. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study. Int J Stroke. 2018 Apr;13(3):328-334. doi: 10.1177/1747493017733935. Epub 2017 Sep 27.

    PMID: 28952914DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

TenecteplaseTissue Plasminogen Activator

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 9, 2015

First Posted

March 13, 2015

Study Start

March 23, 2015

Primary Completion

October 16, 2017

Study Completion

February 1, 2018

Last Updated

March 30, 2018

Record last verified: 2018-03

Locations

AU(16)NZ(2)