Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke

Cerebrovascular Disorders Clinical Trial

Official title:

Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke (EXTEND-AGNES TNK)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05892510
• Other study ID #: CT26024
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: September 1, 2023
• Est. completion date: November 30, 2027

Study information

• Verified date: June 2023
• Source: University of Melbourne
• Contact: Felix Ng
• Phone: +03 9342 7000
• Email: ng.f[@]unimelb.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 462
• Est. completion date: November 30, 2027
• Est. primary completion date: August 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Brain Disorder
• Central Nervous System Diseases
• Cerebrovascular Disorders
• Ischemic Stroke
• Nervous System Diseases
• Stroke

Intervention

Drug:
• 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
• Placebo
intra-arterial bolus of 0.9% Sodium Chloride solution

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Princess Alexandra Hospital	Brisbane
Australia	Royal Brisbane and Women's Hospital	Brisbane
Australia	Canberra Hospital	Canberra
Australia	Alfred Hospital	Melbourne
Australia	Austin Hospital	Melbourne
Australia	Monash Medical Centre	Melbourne
Australia	Royal Melbourne Hospital	Melbourne
Australia	John Hunter Hospital	Newcastle
Australia	Fiona Stanley Hospital	Perth
Australia	Liverpool Hospital	Sydney
Australia	Royal North Shore Hospital	Sydney

Sponsors (1)

Lead Sponsor	Collaborator
University of Melbourne

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early Neurological Improvement (Phase 2b)	Proportion of participants with Early Neurological Improvement (ENI) defined as NIHSS reduction>4	24-36 hours from time of randomisation
Primary	Functional independence (Phase 3)	Proportion of participants with Modified Rankin Scale (mRS) 0-2 (functional independence)	3 months
Secondary	Functional improvement	Reduction of = 1 mRS category (ordinal analysis merging mRS categories 5-6)	3 months
Secondary	Infarct growth	Infarct growth volume on follow-up MRI or CT	24 hours
Secondary	No-reflow	Proportion of participants with radiological no-reflow on MR perfusion or CTP	24 hours
Secondary	Symptomatic Intracerebral Hemorrhage	Proportion of participants with sICH defined as parenchymal haematoma type 2 (PH2) or SAH/IVH within 36 hours combined with neurological deterioration leading to an increase of NIHSS =4 from baseline or leading to death	36 hours
Secondary	All cause mortality	Proportion of participants with death due to any cause	3 months
Secondary	Quality of life assessment on EQ-5D	EQ-5D score	3 months