Clinical trial NCT05892510: Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke
Official title: Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke (EXTEND-AGNES TNK)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Ischemic Stroke, Acute
Cerebrovascular Disorders
Brain Disorder
Central Nervous System Diseases
Keywords: Tenecteplase
Fibrinolytic agents
Thrombectomy
No-reflow
Lead sponsor: University of Melbourne
Sponsor class: OTHER
First posted: 2023-06-07
Enrollment: 462
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Early Neurological Improvement (Phase 2b)
timeFrame: 24-36 hours from time of randomisation
measure: Functional independence (Phase 3)
timeFrame: 3 months
Secondary outcomes:
measure: Functional improvement
timeFrame: 3 months
measure: Infarct growth
timeFrame: 24 hours
measure: No-reflow
timeFrame: 24 hours
measure: Symptomatic Intracerebral Hemorrhage
timeFrame: 36 hours
measure: All cause mortality
timeFrame: 3 months
measure: Quality of life assessment on EQ-5D
timeFrame: 3 months
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
city: Canberra
country: Australia
facility: Canberra Hospital
city: Melbourne
country: Australia
facility: Alfred Hospital
city: Melbourne
country: Australia
facility: Austin Hospital
city: Melbourne
country: Australia
facility: Monash Medical Centre
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
city: Newcastle
country: Australia
facility: John Hunter Hospital
city: Perth
country: Australia
facility: Fiona Stanley Hospital
city: Sydney
country: Australia
facility: Liverpool Hospital
city: Sydney
country: Australia
facility: Royal North Shore Hospital
Study officials:
References: