Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2)

NCT03340493 | Completed Phase 2 DMC

• 1 other identifier: NTA1401a
• Study Type: interventional
• Target: 300
• Locations: 2 countries
• Sites: 28

Brief Summary

Patients presenting to the emergency department with acute ischemic stroke, who are eligible for standard intravenous thrombolysis 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 either 0.4mg/kg or 0.25mg/kg intravenous tenecteplase before all participants undergo endovascular thrombectomy. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.

Conditions

Ischemic Stroke

Keywords

Stroke; Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Tenecteplase; Fibrinolytic agents; Fibrin Modulating agents; Molecular Mechanisms of Pharmacological Action; Plasminogen; Tissue Plasminogen Activator

Outcome Measures

Primary Outcomes (1)

• mTICI

  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 (5)

• Modified Rankin Scale (mRS)

  at 3 months post stroke

• National Institutes of Health Stroke Scale (NIHSS)

  Initial angiogram (day 0)

• Symptomatic intracranial haemorrhage (SICH)

  Within 36 hours post treatment

• Death

  Up to 3 months post stroke

• Angiographic reperfusion

  Up to 24 hours post treatment

Study Arms (2)

Assigned Interventions

ACTIVE COMPARATOR

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

Drug: Tenecteplase

Tenecteplase

EXPERIMENTAL

Patients will receive intravenous tenecteplase (0.4mg/kg, maximum 40mg, administered as a bolus over \~10 seconds).

Drug: Tenecteplase

Interventions

Tenecteplase DRUG

Tenecteplase 0.25mg/kg and 0.4mg/kg are being used

Also known as: TNK

Assigned Interventions; Tenecteplase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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
• Arterial occlusion on CTA (computed tomography angiography) or MRA (Magnetic Resonance Angiography) 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

Sponsors & Collaborators

• Neuroscience Trials Australia: lead
• The Florey Institute of Neuroscience and Mental Health: collaborator

Study Sites (28)

Albury Hospital

Albury, New South Wales, 2640, Australia

Location

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, 2200, Australia

Location

Campbelltown Hospital

Campbelltown, New South Wales, 2560, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

John Hunter Hospital

Newcastle, New South Wales, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2605, 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

Sunshine Coast University Hospital

Nambour, Queensland, 4560, 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

Ballarat Health Services

Ballarat, Victoria, 3353, 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

Goulburn Valley Health

Shepparton, Victoria, 3630, Australia

Location

Western Heath

St Albans, Victoria, 3021, Australia

Location

Latrobe Regional Hospital

Traralgon, Victoria, 3844, Australia

Location

North East Health Wangaratta

Wangaratta, Victoria, 3677, Australia

Location

South West Healthcare

Warrnambool, Victoria, 3280, Australia

Location

Auckland Hospital

Grafton, Auckland, 1001, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Related Publications (8)

• 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: 38502892 DERIVED

• 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: 36878701 DERIVED

• 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: 36289001 DERIVED

• 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: 35017305 DERIVED

• 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: 34906976 DERIVED

• 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: 33408145 DERIVED

• Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Zhao H, Alemseged F, Ng F, Bailey P, Rice H, de Villiers L, Dewey HM, Choi PMC, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Kraemer T, Krause M, Cordato D, Field D, Ma H, O'Brien B, Clissold B, Miteff F, Clissold A, Cloud GC, Bolitho LE, Bonavia L, Bhattacharya A, Wright A, Mamun A, O'Rourke F, Worthington J, Wong AA, Levi CR, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Part 2 investigators. Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial. JAMA. 2020 Apr 7;323(13):1257-1265. doi: 10.1001/jama.2020.1511.

  PMID: 32078683 DERIVED

• Campbell BC, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Yan B, Thijs V, Desmond PM, Parsons MW, Donnan GA, Davis SM. Determining the optimal dose of tenecteplase before endovascular therapy for ischemic stroke (EXTEND-IA TNK Part 2): A multicenter, randomized, controlled study. Int J Stroke. 2020 Jul;15(5):567-572. doi: 10.1177/1747493019879652. Epub 2019 Sep 30.

  PMID: 31564231 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Stroke; Ischemia; Cerebral Infarction; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms; Infarction; Necrosis

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded core laboratory adjudication of the primary outcome. NIHSS and mRS (secondary outcomes) performed by blinded assessor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will receive either intravenous tenecteplase (0.4mg/kg, maximum 40mg, administered as a bolus over \~10 seconds) or intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over \~10 seconds).

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: November 13, 2017
• Study Start: December 6, 2017
• Primary Completion: July 23, 2019
• Study Completion: February 1, 2020
• Last Updated: March 4, 2020

Record last verified: 2020-03

Locations

AU (26); NZ (2)