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

Phase 2

Not yet recruiting

• Conditions: Cerebrovascular Disorders; Ischemic Stroke, Acute; Brain Disorder; Central Nervous System Diseases
• Interventions: Drug: Placebo; Drug: Intra-arterial tenecteplase injection at the completion of thrombectomy

• Registration Number: NCT05892510
• Lead Sponsor: University of Melbourne

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-26
• Study First Submitted QC: 2023-05-26
• Status Verified: 2023-06
• Study First Posted: 2023-06-07
• Last Update Submitted: 2023-06-13
• Last Update Posted: 2023-06-18
• Study Start: 2023-09-01
• Primary Completion: 2027-08-30
• Study Completion: 2027-11-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 462

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Intra-arterial bolus of placebo (0.9% Sodium Chloride solution) representing standard of care (no intra-arterial thrombolytic treatment).
Intra-arterial tenecteplase injection at the completion of thrombectomy	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

Primary Outcome Measures

Name	Time	Method
Early Neurological Improvement (Phase 2b)	24-36 hours from time of randomisation	Proportion of participants with Early Neurological Improvement (ENI) defined as NIHSS reduction\>4
Functional independence (Phase 3)	3 months	Proportion of participants with Modified Rankin Scale (mRS) 0-2 (functional independence)

Secondary Outcome Measures

Name	Time	Method
All cause mortality	3 months	Proportion of participants with death due to any cause
Quality of life assessment on EQ-5D	3 months	EQ-5D score
Infarct growth	24 hours	Infarct growth volume on follow-up MRI or CT
Functional improvement	3 months	Reduction of ≥ 1 mRS category (ordinal analysis merging mRS categories 5-6)
No-reflow	24 hours	Proportion of participants with radiological no-reflow on MR perfusion or CTP
Symptomatic Intracerebral Hemorrhage	36 hours	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

Trial Locations

Locations (12)

Alfred Hospital; 🇦🇺 Melbourne, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

John Hunter Hospital; 🇦🇺 Newcastle, Australia

Canberra Hospital; 🇦🇺 Canberra, Australia

Austin Hospital; 🇦🇺 Melbourne, Australia

Royal North Shore Hospital; 🇦🇺 Sydney, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Brisbane, Australia

Princess Alexandra Hospital; 🇦🇺 Brisbane, Australia

Monash Medical Centre; 🇦🇺 Melbourne, Australia

Royal Melbourne Hospital; 🇦🇺 Melbourne, Australia

Fiona Stanley Hospital; 🇦🇺 Perth, Australia

Liverpool Hospital; 🇦🇺 Sydney, Australia