Direct Endovascular Treatment Versus Bridging Treatment In Basilar Artery Occlusive Stroke

Study Overview
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Brief Summary
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Two recent randomized controlled trials (BAOCHE and ATTENTION) have confirmed the efficacy and safety of endovascular therapy in patient with acute ischemic stroke (AIS) due to basilar artery occlusion (BAO). However, it is still inconclusive whether there is any differences between endovascular therapy with or without bridging intravenous thrombolysis in acute BAO. So far, no randomized controlled trial has been conducted specifically for endovascular therapy with or without intravenous thrombolysis for ischemic stroke due to BAO. Therefore, this study plans to conduct a prospective, multicenter, randomized controlled trial to compare the functional outcomes between endovascular therapy with and without intravenous thrombolysis in patient with AIS due to BAO. This study is a multicenter, parallel, open label, randomized controlled trial comparing direct endovascular therapy versus endovascular therapy bridging intravenous thrombolysis (IVT). This study intends to include patients with AIS due to BAO fulfilling the following inclusion criteria: patients with AIS caused by BAO confirmed by CTA/MRA/DSA; IVT can be started within 4.5 hours after symptoms onset; Age ≥ 18 years old; NIHSS score ≥ 6. The main outcome is the 3-month mRS scale score. Secondary outcomes included NIHSS at 24 hours and 7 days after surgery, CTA vascular recanalization at 24-72 hours, mRS at 5-7 days, and infarct volume. The safety outcomes included 90-day mortality and the incidence of sICH.

Official Title
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Endovascular Treatment With Or Without Intravenous Alteplase In Acute Ischemic Stroke Of Basilar Artery Occlusion: A Multicenter, Prospective, Randomized Controlled Trial (BEST-BAO)

Conditions
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Acute Ischemic Stroke, Basilar Artery Occlusion, Thrombosis, Alteplase, Endovascular Treatment

Intervention / Treatment
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* Procedure: Endovascular treatment
* Drug: Intravenous thrombolysis (Alteplase)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical diagnosis of acute ischemic stroke (AIS); Caused by basilar artery occlusion (BAO) confirmed by CTA, MRA, or DSA; CT or MRI ruling out intracranial hemorrhage; Eligible for intravenous thrombolysis (IVT) and endovascular treatment (EVT) (within 4.5 hours after symptom onset); A score of at least 6 on the NIHSS score; Age of 18 years or older; Written informed consent. Exclusion Criteria: Pre-stroke disability which interferes with the assessment of functional outcome at 90 days, i.e. mRS >2 Any contra-indication for intravenous thrombolysis (IVT), according to guidelines of the American Heart Association, i.e.: Arterial blood pressure exceeding 185/110 mmHg Blood glucose less than 2.7 or over 22.2 mmol/L Cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of recent infarction on neuro-imaging Serious head trauma in the previous 3 months Major surgery or serious trauma in the previous 2 weeks Gastrointestinal or urinary tract hemorrhage in the previous 3 weeks Previous intracerebral hemorrhage Use of anticoagulant with INR exceeding 1.7 Known thrombocyte count less than 100 x 10^9/L Treatment with direct thrombin or factor X inhibitors Treatment with heparin (APTT exceeds the upper limit of normal value) in the previous 48 hours.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Direct endovascular treatment group<br>Direct endovascular treatment (EVT) without intravenous thrombolysis (IVT) | Procedure: Endovascular treatment<br>* It is the emergency surgical removal of emboli which are blocking blood circulation. The strategies that were used for endovascular treatment included stent retrievers, thromboaspiration, balloon angioplasty, stent deployment, intraarterial thrombolysis (with alteplase), or combinations of these approaches that were left to the discretion of the treating team.<br>|
| Active Comparator: Bridging treatment group<br>Intravenous thrombolysis (IVT) followed by endovascular treatment (EVT) | Procedure: Endovascular treatment<br>* It is the emergency surgical removal of emboli which are blocking blood circulation. The strategies that were used for endovascular treatment included stent retrievers, thromboaspiration, balloon angioplasty, stent deployment, intraarterial thrombolysis (with alteplase), or combinations of these approaches that were left to the discretion of the treating team.<br>Drug: Intravenous thrombolysis (Alteplase)<br>* Alteplase is used in the intravenous thrombolysis. It catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mRS (the modified Rankin Scale) score | The mRS score is an ordinal hierarchical scale ranging from 0 to 5, with higher scores suggesting more severe disability. | At 90 day after procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NIHSS (the National Institutes of Health Stroke Scale) score | The NIHSS score is an ordinal hierarchical scale to evaluate the symptomatic severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores suggesting a more severe deficit. | At 24 hours and 5-7 days after procedure | 
| Recanalization rate | The recanalization rate at 24-72 hours after endovascular treatment, assessed by computerized tomographic angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography (DSA). | At 24-48 hours after endovascular treatment | 
| Final infarct volume | The final infarct volume will be assessed with the use of an automated, validated algorithm based on magnetic resource imaging test. | At 5-7 days after procedure | 
| All-cause mortality | The proportion of total deaths caused by various reasons in both arms | At 90 days after procedure | 
| eTICI (Extended Treatment In Cerebral Ischemia) score | The eTICI is an ordinal hierarchical scale ranging from 0 to 3, with higher scores suggesting better antegrade reperfusion of the previously occluded target artery ischemic territory. | Immediately after endovascular treatment | 
| sICH (symptomatic intracranial hemorrhage) rate | The sICH means any hemorrhage with neurological deterioration, as indicated by an NIHSS score that was higher by ≥4 points than the value at baseline or the lowest value in the first 7 days or any hemorrhage leading to death. | At 7 days after endovascular treatment | 
| Comparison of mRS 0-1 and mRS 2-6 | The mRS score is an ordinal hierarchical scale ranging from 0 to 5, with higher scores suggesting more severe disability. | At 90 days after procedure | 
| Comparison of mRS 0-2 and mRS 3-6 | The mRS score is an ordinal hierarchical scale ranging from 0 to 5, with higher scores suggesting more severe disability. | At 90 days after procedure | 
| Comparison of mRS 0-3 and mRS 4-6 | The mRS score is an ordinal hierarchical scale ranging from 0 to 5, with higher scores suggesting more severe disability. | At 90 days after procedure | 
| EQ-5D-5L (the European Quality of Life 5-Dimension 5-Level) score | The EQ-5D-5L score is an ordinal hierarchical scale to evaluate the quality of life. Scores range from -0.39 to 1, with higher scores indicating a better quality of life. | At 90 days after procedure | 
| Barthel Index | dichotomized as 0 to 94 The Barthel Index is an ordinal hierarchical scale to evaluate the daily activities. Scores range from 0 to 100. The Barthel Index will be dichotomized as 0 to 94 vs. 95 to 100, with a score of 95 to 100 indicating no interference with daily activities. | At 90 days after procedure | 
| Proportion of new cerebral infarction | The proportion of the new cerebral infarction compared with the onset of symptoms evaluated with magnetic resource imaging test | At 5-7 days after procedure | 
| Incidence of pseudoaneurysm at puncture site | The pseudoaneurysm at puncture site caused by various reasons is one of the important indicators reflecting puncture complications. | At 5-7 days after procedure | 
| Incidence of hematoma at puncture site | The hematoma at puncture site caused by various reasons is one of the important indicators reflecting puncture complications. | At 5-7 days after procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, Endovascular treatment, Alteplase, Basilar artery occlusion, Intravenous thrombosis