Acute Ischemic Stroke, Basilar Artery Occlusion
Conditions
Keywords
basilar artery occlusion, thrombolysis, interhospital transfer
Brief summary
This study is designed to investigate the efficacy and safety of intravenous tenecteplase before interhospital transfer from a non-endovascular capable center(nECC) to an endovascular capable center (ECC) for thrombectomy in patients with acute ischemic stroke (AIS) caused by neuroimaging-confirmed acute basilar artery occlusion (BAO) between 4.5-24 hours of symptom onset.
Detailed description
This is a multicenter, prospective, open-label, blinded endpoint (PROBE), randomized controlled trial in patients with acute ischemic stroke due to BAO first presenting to a nECC and intending to undertake thrombectomy in an ECC. Patients will be required to have occlusion of the basilar artery on baseline computed tomography angiography (CTA)/magnetic resonance angiography (MRA) at the nECC. Patients will be randomized to either intravenous tenecteplase (0.25mg/kg, maximum 25mg)or not before interhospital transfer.
Interventions
DRUGTenecteplase thrombolysis
Patients will receive intravenous Tenecteplase 0.25 mg/kg body-weight up to a maximum of 25mg before the transfer. A single bolus dose should be administered over 5-10 seconds based on patient weight. Transfer to ECCs for thrombectomy should be initiated immediately after Tenecteplase administration.
Sponsors
Xuanwu Hospital, Beijing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years; * Patients presenting with posterior circulation ischemic stroke symptoms due to BAO; * BAO confirmed by computed tomographic angiography (CTA)/ magnetic resonance angiography (MRA); * Time from AIS symptom onset to randomization within 4.5-24 hours, stroke onset is defined as the onset of acute symptoms leading to the clinical diagnosis of basilar artery occlusion (BAO) not considering the time of any preceding minor prodromal symptoms (such as isolated vertigo, diplopia or sensory changes) as onset time or, if not known, the time the patient was last known to be well (including wake-up stroke and unwitnessed stroke); * Baseline National Institute of Health Stroke Scale (NIHSS) score obtained prior to randomization ≥6; * Functionally independent (modified Rankin Scale \[mRS\] 0-2) prior to stroke onset; * Intended to transfer for thrombectomy. Two paradigms are allowed in this study: (1)transferring patients to ECC (patient transfer); (2)travelling neurointerventionist to nECC (physician transfer); * Written informed consent from patients or legally responsible representatives
Exclusion criteria
* Posterior Circulation Acute Stroke Prognosis Early CT score (PC-ASPECTS) \< 6 on computed tomography (CT)/CTA-Source Images/MRI with diffusion-weighted imaging (DWI) * CT/MR shows evidence of intracranial hemorrhage and tumor (except small meningioma) * Complete cerebellar infarct on CT/MRI with significant mass effect and compression of the 4th ventricle * Bilateral extensive brainstem infarction on CT/MRI * Simultaneous occlusion of both anterior and posterior circulation confirmed by CTA/MRA/DSA (patients with a history of occlusion of anterior circulation more than three months ago can be included) * Treatment with a thrombolytic within the last 72 hours or intention to receive intravenous thrombolysis * Known hypersensitivity or allergy to any ingredients of Tenecteplase * Any other contra-indication for intravenous thrombolysis except for the time criteria * Known hereditary or acquired hemorrhagic diathesis * Impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, international normalized ratio (INR) \>1.7 or prothrombin time \>15s; if use of any direct oral anticoagulant within the last 48 hours; if use of heparin/heparinoid within the last 24 hours * Ischemic stroke or myocardial infarction in previous 3 months * Previous intracranial hemorrhage, active internal bleeding (gastrointestinal or urinary tract hemorrhage) in previous 3 months * Severe, uncontrolled hypertension (systolic blood pressure \>185mmHg or diastolic blood pressure \>110mmHg) * Baseline blood glucose \<50mg/dl or \>400mg/dl * Baseline platelet count \<100,000/μL * Undergoing hemodialysis or peritoneal dialysis; known severe renal insufficiency with glomerular filtration rate \<30mL/min or serum creatinine \>220mmol/L (2.5mg/dL) * Known severe, life-threatening allergy (more severe than skin rash) to contrast agents * Patients with acute stroke within the first 48 hours after percutaneous cardiac, cerebrovascular interventions and major surgery * Known diagnosis or clinical suspicion of cerebral vasculitis * Known diagnosis or clinical suspicion of endocarditis * Pregnancy or lactating; * Other serious, advanced or terminal illness with life expectancy less than 6 months * Current participation in any investigational study that may confound outcome assessment of the study * Any condition that, in the judgement of the investigator, is inappropriate for participation in the trial or could impose hazards to the patient (e.g. inability to understand and/or follow the study procedures and/or follow-up due to mental disorders, cognitive or emotional disorders)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dichotomized mRS of 0-2 vs. 3-6 | 90±7 days | Dichotomized mRS of 0-2 vs. 3-6 at 90±7 days; modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal mRS score | 90 (±7) days | Ordinal mRS score at 90 (±7) days; modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but remaining able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death) |
| Dichotomized mRS of 0-1 vs. 2-6 | 90 (±7) days | Dichotomized mRS of 0-1 vs. 2-6 at 90 (±7) days |
| Dichotomized mRS of 0-3 vs. 4-6 | 90 (±7) days | Dichotomized mRS of 0-3 vs. 4-6 at 90 (±7) days |
| Early dramatic clinical response rate | 24 (±12) hours | Early dramatic clinical response rate at 24 (±12) h, defined as a NIHSS score of 0 or 2 or NIHSS drop of ≥8 from baseline |
| Arterial recanalization during interhospital transfer | At ECC before thrombectomy or physician-arrival | Arterial recanalization during interfacility transfer, evaluated with the angiography (CTA/MRA/first run of DSA) at ECC |
| Successful reperfusion | At end-of-procedure angiography (up to 15 minutes) | Successful reperfusion at end-of-procedure angiography, defined as expanded Treatment in Cerebral Infarction (eTICI) score of 2b, 2c, or 3 on angiography |
| First pass excellent reperfusion | Immediately after the thrombectomy | First pass reperfusion defined as eTICI 2c or greater after the first thrombectomy pass |
| Arterial recanalization | 24(±12) hours | Arterial recanalization at 24(±12)h, evaluated with CTA/MRA |
| EQ-5D-5L | 90 (±7) days | Score on the EQ-5D-5L at 90 (±7) days;(EQ-5D-5L: Minimum Score 5, Maximum score 25, lower scores mean a better quality of life). |
Countries
China
Contacts
CONTACTJunwei Hao, MD
CONTACTGaoting Ma, MD
PRINCIPAL_INVESTIGATORJunwei Hao, MD
Xuanwu Hospital, Beijing
Outcome results
None listed