Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05892510




Registration number
NCT05892510
Ethics application status
Date submitted
26/05/2023
Date registered
7/06/2023
Date last updated
18/06/2023

Titles & IDs
Public title
Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke
Scientific title
Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke (EXTEND-AGNES TNK)
Secondary ID [1] 0 0
CT26024
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischemic Stroke, Acute 0 0
Cerebrovascular Disorders 0 0
Brain Disorder 0 0
Central Nervous System Diseases 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Intra-arterial tenecteplase injection at the completion of thrombectomy
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Intra-arterial bolus of placebo (0.9% Sodium Chloride solution) representing standard of care (no intra-arterial thrombolytic treatment).

Experimental: Intra-arterial tenecteplase injection at the completion of thrombectomy - intra-arterial tenecteplase (0.062mg/kg, maximum 6.25mg) administered as a bolus at the completion of thrombectomy through a microcatheter at the site of the initial-but-now-retrieved intracranial occlusion or in direct contact with the residual thrombus


Treatment: Drugs: Intra-arterial tenecteplase injection at the completion of thrombectomy
Intra-arterial tenecteplase (0.062mg/kg, maximum 6.25mg) administered as a bolus at the completion of thrombectomy through a microcatheter at the site of the initial-but-now-retrieved intracranial occlusion, or in direct contact with the residual thrombus

Treatment: Drugs: Placebo
intra-arterial bolus of 0.9% Sodium Chloride solution
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Early Neurological Improvement (Phase 2b)
Timepoint [1] 0 0
24-36 hours from time of randomisation
Primary outcome [2] 0 0
Functional independence (Phase 3)
Timepoint [2] 0 0
3 months
Secondary outcome [1] 0 0
Functional improvement
Timepoint [1] 0 0
3 months
Secondary outcome [2] 0 0
Infarct growth
Timepoint [2] 0 0
24 hours
Secondary outcome [3] 0 0
No-reflow
Timepoint [3] 0 0
24 hours
Secondary outcome [4] 0 0
Symptomatic Intracerebral Hemorrhage
Timepoint [4] 0 0
36 hours
Secondary outcome [5] 0 0
All cause mortality
Timepoint [5] 0 0
3 months
Secondary outcome [6] 0 0
Quality of life assessment on EQ-5D
Timepoint [6] 0 0
3 months

Eligibility
Key inclusion criteria
- Adult participants (age=18 years) presenting with ischemic stroke with arterial LVO on
CT/MR Angiogram of the intracranial internal carotid or middle cerebral artery (MCA)
first segment (M1) or proximal second segment (M2) committed to thrombectomy using
standard criteria within 24 hours of onset:

- For 0-6 hours of symptom onset: Presence of arterial occlusion as defined above and
ASPECTS=3 on NCCT

- For 6-24 hours of symptom onset: Additional imaging criteria on CTP or MRI perfusion
of core volume <100ml.

- Qualifying CT/MR within 4hrs of randomisation (repeat CT for transferred participants
required if >4hr)

- Pre-stroke Modified Rankin Scale (mRS) score of =2 (mild pre-existing disability
permitted)

- Local legal requirements for consent have been satisfied.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Intracranial hemorrhage identified by CT or MRI

- ASPECTS 0-2 on NCCT

- CTP or MRI perfusion ischemic core volume >100ml if presenting within 6-24 hours from
symptoms onset

- Anticipated endovascular stenting required for intracranial or extracranial
atherosclerotic stenosis/occlusion.

- More than six retrieval attempts in the same vessel

- Alteplase being infused within 30 minutes (~5x half-life) of anticipated trial drug
administration

- Contraindication to imaging with contrast agents

- Any condition (eg.mid-arterial phase early venous filling) that in the judgment of
investigators could impose hazards if study therapy is initiated

- Pregnant women.

- Current participation in another intervention research study that includes
experimental interventions beyond standard-of-care.

- Anticoagulation. INR =1.7 if on warfarin, and dabigatran reversal by idarucizumab are
permitted.

- Other standard contraindications to thrombolysis apart from time window.

- Known terminal illness such that the participants would not be expected to survive a
year.

- Planned withdrawal of care or comfort care measures.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/09/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/11/2027
Actual
Sample size
Target
462
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [4] 0 0
Canberra Hospital - Canberra
Recruitment hospital [5] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [6] 0 0
Austin Hospital - Melbourne
Recruitment hospital [7] 0 0
Monash Medical Centre - Melbourne
Recruitment hospital [8] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [9] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [10] 0 0
Fiona Stanley Hospital - Perth
Recruitment hospital [11] 0 0
Liverpool Hospital - Sydney
Recruitment hospital [12] 0 0
Royal North Shore Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Canberra
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- Newcastle
Recruitment postcode(s) [6] 0 0
- Perth
Recruitment postcode(s) [7] 0 0
- Sydney

Funding & Sponsors
Primary sponsor type
Other
Name
University of Melbourne
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Multicentre, prospective, Multi-arm Multi-stage (MAMS) seamless phase 2b/3 interventional
randomized placebo-controlled double-blinded parallel-assignment (2 arms with 1:1
randomization) efficacy and safety trial to test intra-arterial tenecteplase at the
completion of thrombectomy versus best practice in participants with anterior circulation LVO
receiving mechanical thrombectomy within 24 hours of symptoms onset.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05892510
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Felix Ng
Address 0 0
Country 0 0
Phone 0 0
+03 9342 7000
Fax 0 0
Email 0 0
ng.f@unimelb.edu.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05892510