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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02388061

Registration number

NCT02388061

Ethics application status

Date submitted

9/03/2015

Date registered

13/03/2015

Date last updated

30/03/2018

Titles & IDs

Public title

Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke

Scientific title

Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial Using Intravenous Tenecteplase

Secondary ID [1]

NTA1401

Universal Trial Number (UTN)

Trial acronym

EXTEND-IA TNK

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Ischemic Stroke

Condition category

Condition code

Stroke

Ischaemic

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

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

Active comparator: Intravenous tissue plasminogen activator (tPA) - 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.

Comparator / control treatment

Control group

Outcomes

Primary outcome [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.

Timepoint [1]

Initial angiogram (day 0)

Secondary outcome [1]

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.

Timepoint [1]

Initial angiogram (day 0)

Secondary outcome [2]

Modified Rankin Scale (mRS) at 3 months

Timepoint [2]

3 months post stroke

Secondary outcome [3]

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

Timepoint [3]

3 months post stroke

Secondary outcome [4]

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

Timepoint [4]

3 months post stroke

Secondary outcome [5]

Symptomatic intracranial hemorrhage (SICH)

Timepoint [5]

within 36 hours post treatment

Secondary outcome [6]

Death due to any cause

Timepoint [6]

Up to 3 months post stroke

Secondary outcome [7]

Proportion of patients with angiographic reperfusion adjusted for hyperdense clot length on non-contrast CT and time from thrombolysis to initial angiogram

Timepoint [7]

Up to 24 hours post treatment

Eligibility

Key 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.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key 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

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 2

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

23/03/2015

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

1/02/2018

Sample size

Target

Accrual to date

Final

202

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,VIC

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [2]

Gosford Hospital - Gosford

Recruitment hospital [3]

John Hunter Hospital - Newcastle

Recruitment hospital [4]

Royal North Shore Hospital - St. Leonards

Recruitment hospital [5]

Westmead Hospital - Westmead

Recruitment hospital [6]

Royal Brisbane & Women's Hospital - Brisbane

Recruitment hospital [7]

Gold Coast University Hospital - Gold Coast

Recruitment hospital [8]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [9]

Royal Adelaide Hospital - Adelaide

Recruitment hospital [10]

Lyell McEwin Hospital - Elizabeth Vale

Recruitment hospital [11]

Box Hill Hospital - Box Hill

Recruitment hospital [12]

Monash Medical Centre - Clayton

Recruitment hospital [13]

Austin Hospital - Heidelberg

Recruitment hospital [14]

Alfred Hospital - Melbourne

Recruitment hospital [15]

Royal Melbourne Hospital - Melbourne

Recruitment hospital [16]

Western Heath - St Albans

Recruitment postcode(s) [1]

2050 - Camperdown

Recruitment postcode(s) [2]

2250 - Gosford

Recruitment postcode(s) [3]

- Newcastle

Recruitment postcode(s) [4]

2065 - St. Leonards

Recruitment postcode(s) [5]

2145 - Westmead

Recruitment postcode(s) [6]

- Brisbane

Recruitment postcode(s) [7]

- Gold Coast

Recruitment postcode(s) [8]

4102 - Woolloongabba

Recruitment postcode(s) [9]

5000 - Adelaide

Recruitment postcode(s) [10]

5112 - Elizabeth Vale

Recruitment postcode(s) [11]

3128 - Box Hill

Recruitment postcode(s) [12]

3168 - Clayton

Recruitment postcode(s) [13]

- Heidelberg

Recruitment postcode(s) [14]

3004 - Melbourne

Recruitment postcode(s) [15]

3050 - Melbourne

Recruitment postcode(s) [16]

3021 - St Albans

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Country [2]

New Zealand

State/province [2]

Christchurch

Funding & Sponsors

Primary sponsor type

Other

Name

Neuroscience Trials Australia

Address

Country

Other collaborator category [1]

Other

Name [1]

The Florey Institute of Neuroscience and Mental Health

Address [1]

Country [1]

Ethics approval

Ethics application status

Summary

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 website

https://clinicaltrials.gov/study/NCT02388061

Trial related presentations / publications

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.
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.
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.
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.
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.
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.
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.

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02388061

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02388061