Brain Disorder, Central Nervous System Diseases, Cerebrovascular Disorders, Ischemic Stroke, Acute
Conditions
Keywords
Tenecteplase, Fibrinolytic agents, Thrombectomy, No-reflow
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.
Interventions
DRUGIntra-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
DRUGPlacebo
intra-arterial bolus of 0.9% Sodium Chloride solution
Sponsors
University of Melbourne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Functional improvement | 3 months | Reduction of ≥ 1 mRS category (ordinal analysis merging mRS categories 5-6) |
| Infarct growth | 24 hours | Infarct growth volume on follow-up MRI or CT |
| 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 |
| 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 |
Countries
Australia, New Zealand
Contacts
CONTACTFelix Ng
Outcome results
None listed