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Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK)

Primary Purpose

Ischemic Stroke

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tenecteplase
Tissue Plasminogen Activator
Sponsored by
Neuroscience Trials Australia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

  1. Intracranial hemorrhage (ICH) identified by CT or MRI
  2. Rapidly improving symptoms at the discretion of the investigator
  3. Pre-stroke mRS score of ≥ 4 (indicating previous disability)
  4. Hypodensity in >1/3 MCA territory or equivalent proportion of basilar artery territory on non-contrast CT
  5. Contra indication to imaging with contrast agents
  6. Any terminal illness such that patient would not be expected to survive more than 1 year
  7. 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.
  8. Pregnant women

Sites / Locations

  • Royal Prince Alfred Hospital
  • Gosford Hospital
  • John Hunter Hospital
  • Royal North Shore Hospital
  • Westmead Hospital
  • Royal Brisbane & Women's Hospital
  • Gold Coast University Hospital
  • Princess Alexandra Hospital
  • Royal Adelaide Hospital
  • Lyell McEwin Hospital
  • Box Hill Hospital
  • Monash Medical Centre
  • Austin Hospital
  • Alfred Hospital
  • Royal Melbourne Hospital
  • Western Heath
  • Auckland Hospital
  • Christchurch Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intravenous tenecteplase (TNK)

Intravenous tissue plasminogen activator (tPA)

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Modified Rankin Scale (mRS) at 3 months
ordinal analysis
mRS 0-1 or no change from baseline at 3 months
mRS 0-2 or no change from baseline at 3 months
Symptomatic intracranial hemorrhage (SICH)
Death due to any cause
Proportion of patients with angiographic reperfusion adjusted for hyperdense clot length on non-contrast CT and time from thrombolysis to initial angiogram

Full Information

First Posted
March 9, 2015
Last Updated
March 28, 2018
Sponsor
Neuroscience Trials Australia
Collaborators
The Florey Institute of Neuroscience and Mental Health
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1. Study Identification

Unique Protocol Identification Number
NCT02388061
Brief Title
Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke
Acronym
EXTEND-IA TNK
Official Title
Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial Using Intravenous Tenecteplase
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
March 23, 2015 (Actual)
Primary Completion Date
October 16, 2017 (Actual)
Study Completion Date
February 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neuroscience Trials Australia
Collaborators
The Florey Institute of Neuroscience and Mental Health

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
202 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intravenous tenecteplase (TNK)
Arm Type
Experimental
Arm Description
Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over ~10 seconds).
Arm Title
Intravenous tissue plasminogen activator (tPA)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tenecteplase
Other Intervention Name(s)
TNK
Intervention Type
Drug
Intervention Name(s)
Tissue Plasminogen Activator
Other Intervention Name(s)
Alteplase, tPA
Primary Outcome Measure Information:
Title
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.
Time Frame
Initial angiogram (day 0)
Secondary Outcome Measure Information:
Title
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.
Time Frame
Initial angiogram (day 0)
Title
Modified Rankin Scale (mRS) at 3 months
Description
ordinal analysis
Time Frame
3 months post stroke
Title
mRS 0-1 or no change from baseline at 3 months
Time Frame
3 months post stroke
Title
mRS 0-2 or no change from baseline at 3 months
Time Frame
3 months post stroke
Title
Symptomatic intracranial hemorrhage (SICH)
Time Frame
within 36 hours post treatment
Title
Death due to any cause
Time Frame
Up to 3 months post stroke
Title
Proportion of patients with angiographic reperfusion adjusted for hyperdense clot length on non-contrast CT and time from thrombolysis to initial angiogram
Time Frame
Up to 24 hours post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Facility Information:
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Gosford Hospital
City
Gosford
State/Province
New South Wales
ZIP/Postal Code
2250
Country
Australia
Facility Name
John Hunter Hospital
City
Newcastle
State/Province
New South Wales
Country
Australia
Facility Name
Royal North Shore Hospital
City
St. Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Royal Brisbane & Women's Hospital
City
Brisbane
State/Province
Queensland
Country
Australia
Facility Name
Gold Coast University Hospital
City
Gold Coast
State/Province
Queensland
Country
Australia
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Lyell McEwin Hospital
City
Elizabeth Vale
State/Province
South Australia
ZIP/Postal Code
5112
Country
Australia
Facility Name
Box Hill Hospital
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Austin Hospital
City
Heidelberg
State/Province
Victoria
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Western Heath
City
St Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Facility Name
Auckland Hospital
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1001
Country
New Zealand
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand

12. IPD Sharing Statement

Citations:
PubMed Identifier
36289001
Citation
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.
Results Reference
derived
PubMed Identifier
35017305
Citation
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.
Results Reference
derived
PubMed Identifier
34906976
Citation
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.
Results Reference
derived
PubMed Identifier
33408145
Citation
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.
Results Reference
derived
PubMed Identifier
33023423
Citation
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.
Results Reference
derived
PubMed Identifier
29694815
Citation
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.
Results Reference
derived
PubMed Identifier
28952914
Citation
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.
Results Reference
derived

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Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke

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