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).
Patients presenting with posterior circulation ischemic stroke symptoms due to partial or complete basilar artery occlusion within 24 hours from symptom onset (or clinical deterioration/coma) or the time the patient was last known to be well.
Patient's age is ≥18 years
Presence of basilar artery occlusion, proven by CT Angiography or MR Angiography. Basilar artery occlusion is defined as 'potentially retrievable' occlusion at the basilar artery. This can be a partial or complete occlusion.
Premorbid mRS ≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week).
Intracerebral hemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baseline imaging.
Posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) <7 on non-contrast CT, CT Angiography source images or DWI MRI.
Significant cerebellar mass effect or acute hydrocephalus.
Established frank hypodensity on non-contrast CT indicating subacute infarction.
Parallel
Tenecteplase
DrugGenetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as an intravenous bolus over 5-10 seconds.
Standard Care (which may include intravenous Alteplase)
DrugPatients will receive standard care which may include intravenous alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as a bolus and the remainder as an infusion over 1 hour.
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
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
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
Ordinal analysis of the mRS at 90 days
Ordinal analysis of the mRS, merging category 5-6, at 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).
Intermediate outcome (Stage 1): Partial or complete recanalization of the basilar artery without sICH
Proportion of patients achieving partial or complete recanalization of the basilar artery on initial digital subtraction angiography (DSA) prior to thrombectomy or repeat CT Angiography (if DSA not performed) without symptomatic intracerebral hemorrhage (sICH). Partial or complete recanalization is defined as reperfusion of ≥50% of the affected territory or absence of retrievable thrombus.
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