The trial is a multicentre, prospective, open-label, blinded endpoint (PROBE), phase 3, randomized controlled design. Patients with acute ischemic stroke due to basilar artery occlusion presenting within 24 hours will be randomized 1:1 to intravenous tenecteplase (0.25mg/kg, maximum 25mg) ± thrombectomy or 'best practice'which may be alteplase (0.9mg/kg) within 4.5 hours from stroke onset or standard care (no lysis) ± thrombectomy at treating clinician's discretion.
The study will be a multicentre, prospective, open-label, blinded endpoint (PROBE), randomized controlled trial (2 arm with 1:1 randomization) in patients with acute ischemic stroke due to basilar artery occlusion presenting to hospital within 24 hours of symptom onset. Patients will be required to have complete or near-complete occlusion of the basilar artery on baseline computed tomography angiography (CTA)/magnetic resonance angiography (MRA), defined as 'potentially retrievable' thrombus in the basilar artery. Thrombectomy is permitted within 24 hours as part of standard care but is not mandatory. Patients will be randomized to treatment with either standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg within 4.5 hours from stroke onset) or intravenous tenecteplase (0.25mg/kg, maximum 25mg). Time of onset of symptoms is defined as described by the patient or witness; if unknown, it is considered to be the last time the patient was seen well. In patients presenting with mild (e.g. vertigo, dizziness, headache, diplopia, dysarthria) stuttering symptoms followed by sudden onset of clinical deterioration with decrease in conscious state or moderate to severe motor deficits, the time of deterioration in clinical state is taken as the estimated time of basilar artery occlusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
452
Intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds) within 24 hours ± thrombectomy at treating clinician's discretion
Intravenous alteplase (0.9mg/kg) within 4.5 hours from stroke onset or standard care (no lysis) ± thrombectomy at treating clinician's discretion
Modified Rankin Scale (mRS) 0-1 or return to baseline mRS
The proportion of patients with Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2-3) at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).
Time frame: 3 months
Modified Rankin Scale (mRS) 0-2 or return to baseline mRS
Proportion of patients with Modified Rankin Scale (mRS) 0-2 or return to baseline mRS at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).
Time frame: 3 months
Modified Rankin Scale (mRS) 0-3 or return to baseline mRS
Proportion of patients with Modified Rankin Scale (mRS) 0-3 or return to baseline mRS at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).
Time frame: 3 months
Ordinal analysis of the Modified Rankin Scale (mRS)
Ordinal analysis of the Modified Rankin Scale (mRS), merging category 5-6, at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).
Time frame: 3 months
Early neurological improvement
Proportion of patients achieving early clinical improvement (reduction in acute - 72 hour National Institutes of Health Stroke Scale \[NIHSS\] score of ≥8 or 72 hour NIHSS 0-1).
Time frame: 72 hours
Successful reperfusion
Proportion of patients with complete occlusion at baseline who achieve expanded Thrombolysis In Cerebral Infarction score (eTICI) 2b/3 on initial digital subtraction angiography (DSA) run prior to thrombectomy.
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Taihe County Traditional Chinese Medicine Hospital
Fuyang, Anhui, China
Lixin County People's Hospital
Haozhou, Anhui, China
Beijing Tian Tan Hospital, Capital Medical University
Beijing, Beijing Municipality, China
First People's Hospital of Tianshui
Tianshui, Gansu, China
Guangdong Second Provincial General Hospital
Guangzhou, Guangdong, China
Heyuan People's Hospital
Heyuan, Guangdong, China
Huazhou People's Hospital
Huazhou, Guangdong, China
Shaoguan Qujiang District People's Hospital
Shaoguan, Guangdong, China
The Second Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, China
The Second People's Hospital of Guiyang
Guiyang, Guizhou, China
...and 49 more locations
Time frame: initial DSA run prior to thrombectomy
Symptomatic intracranial hemorrhage (sICH)
Proportion of patients with symptomatic intracranial hemorrhage (sICH) defined as local or remote parenchymal hemorrhage type 2 (PH2) on the 22-36 hours post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 hours, or leading to death.
Time frame: 36 hours
All-cause mortality
All-cause mortality within 90 days.
Time frame: 90 days
Severe disability or death
Proportion of patients with Modified Rankin Scale (mRS) 5-6 at 90 days (severe disability or death). Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).
Time frame: 90 days
Clinical deterioration
Proportion of patients with partially occlusive thrombus at baseline who have clinical deterioration within 24 hours leading to further treatment (e.g. endovascular thrombectomy).
Time frame: 24 hours
Vessel recanalization
Vessel recanalization rate evaluated by CT or MR angiography within 24+/-6 hours (if performed).
Time frame: 24+/-6 hours