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Extending the Time Window for Tenecteplase by Recanalization of Basilar Artery Occlusion in Posterior Circulation Stroke
Patients presenting to the emergency department with an acute ischemic stroke due to basilar artery occlusion within 24 hours of stroke onset will be assessed to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomised 50:50 using a central computerised allocation process to either standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0. 9mg/kg) or tenecteplase 0.
25mg/kg before undergoing mechanical thrombectomy as required at treating clinician's discretion. The trial is Multi-arm, Multi-stage, prospective, randomised, open-label, blinded endpoint (PROBE) design with seamless phase 2b/3 transition if the intermediate endpoint (recanalization without symptomatic intracerebral hemorrhage) is met in analysis of the first 202 patients. Adaptive sample size re-estimation (Mehta and Pocock) will be performed when 240 patients have completed 3 month follow-up (minimum sample size 320, maximum sample size 688).
Study details:
The study is a Multi-Arm Multi-Stage (MAMS), multiregional, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE), controlled seamless phase 2b/3 trial (2 arm with 1:1 randomisation) with adaptive sample size recalculation in patients with stroke due to basilar artery occlusion. Stage 1 will use the surrogate outcome of recanalization without symptomatic intracerebral hemorrhage (sICH) to establish whether proceeding to Stage 2 is warranted. If results in the first n= 202 patients meet success criteria, the trial will seamlessly convert to a phase 3 design using modified Rankin scale 0-1 at 3 months as the primary outcome (minimum n=320 with interim sample size re-estimation at n=240, maximum sample n=688) using the Mehta and Pocock conditional power method.
Each regionally-based stratum will be pooled in the final analysis and analysed as a stratification by geographic region. Randomisation of patients within each stratum will be stratified by the investigator's intention to treat with mechanical thrombectomy (or not) and the investigator's intention to treat with alteplase intravenous thrombolysis should the patient be randomised to the control group (or not). Covariate adjusted minimum sufficient balance randomisation will then be applied to control for age, NIHSS and time from onset-to-randomisation (dichotomized as 0-6 hours vs 6-24 hours).
The primary objective of the study is to test the hypothesis that the thrombolytic tenecteplase (TNK, 0. 25mg/kg) ± mechanical thrombectomy administered within 24 hours after symptoms onset, is superior to current best practice (alteplase, rtPA, 0. 9mg/kg or standard care/no lysis ± mechanical thrombectomy) in achieving excellent functional outcome (mRS 0-1) or return to the premorbid modified Rankin Scale at 90 days in patients with acute ischemic stroke due to basilar artery occlusion.
Estimated study duration is 5 years. Patients will participate in the trial for 12 months.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2021-11-29
Primary completion: 2026-08-01
Study completion finish: 2026-12-01
Study type
TREATMENT
Phase
PHASE2
PHASE3
Trial ID
NCT05105633
Intervention or treatment
DRUG: Tenecteplase
DRUG: Standard Care (which may include intravenous Alteplase)
Conditions
- • Basilar Artery Occlusion
Find a site
Closest Location:
John Hunter Hospital
Research sites nearby
Select from list below to view details:
John Hunter Hospital
Newcastle, New South Wales, Australia
Liverpool Hospital
Sydney, New South Wales, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Intravenous tenecteplase (TNK)
| DRUG: Tenecteplase
|
ACTIVE_COMPARATOR: Standard Care (which may include intravenous Alteplase)
| DRUG: Standard Care (which may include intravenous Alteplase)
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Modified Rankin Scale (mRS) 0-1 or return to baseline mRS at 90 days | Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS 2-3) at 90 days | 90 days |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Modified Rankin Scale 0-2 or return to baseline mRS at 90 days | Proportion of patients with Modified Rankin Scale 0-2 or return to baseline mRS at 90 days | 90 days |
Modified Rankin Scale 0-3 or return to baseline mRS at 90 days | Proportion of patients with Modified Rankin Scale 0-3 or return to baseline mRS at 90 days | 90 days |
Ordinal analysis of the mRS at 90 days | Ordinal analysis of the mRS, merging category 5-6, at 90 days | 90 days |
Early clinical improvement | Proportion of patients achieving early clinical improvement (reduction in acute - 72 hour NIHSS score of ≥8 or 72 hour NIHSS 0-1). | 72 hours |
Substantial reperfusion on initial digital subtraction angiography run prior to thrombectomy | Proportion of patients with complete occlusion at baseline who achieve eTICI 2b/3 on initial digital subtraction angiography run prior to thrombectomy. | Initial angiogram (day 0) |
Quality of Life assessment (EQ-5D) - at 90 days and 12 months | Quality of Life assessment (EQ-5D) - at 90 days and 12 months | 90 days and 12 months |
Symptomatic intracerebral hemorrhage (sICH) | Proportion of patients with sICH defined as parenchymal hemorrhage type 2 (PH2), subarachnoid hemorrhage, and/or intraventricular hemorrhage within 36 of treatment, combined with a neurological deterioration of ≥4 points on the NIHSS from baseline, or leading to death. | 36 hours |
All-cause mortality within 90 days | All-cause mortality within 90 days | 90 days |
Modified Rankin Scale (mRS) 5-6 at 90 days | Proportion of patients with Modified Rankin Scale (mRS) 5-6 at 90 days (severe disability or death) | 90 days |
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