Acute Basilar Artery Occlusion: Endovascular Interventions vs Standard Medical Treatment

Study Overview
=================
Brief Summary
-----------------
This trial will provide valuable insights into the safety and efficacy of endovascular treatment for acute ischemic stroke patients with basilar artery occlusion within 8 hours of estimated occlusion time.

Detailed Description
-----------------
This clinical trial is designed to compare the safety and efficacy of endovascular treatment plus standard medical therapy with standard medical therapy alone for acute BA occlusion presented within 8 h of estimated occlusion time. There is only one ongoing clinical trial-Basilar Artery International Cooperation Study (BASICS) (NCT01717755) aimed to evaluate the efficacy and safety of additional intra-arterial treatment after intravenous treatment in 750 patients with BA occlusion, which was anticipated to be completed in Oct 2017. Initiation of intra-arterial therapy should be feasible within 6 hours of estimated time of BA occlusion. And patients are required to have an NIHSS ≥ 10 at time of randomization, and take IV rt-PA, age between 18-85 years old. In this trial, the investigators did not have age or NIHSS score limit, patients who did not fulfill the requirements for IV rt-PA can also be included into the trial, the investigators also extended the time window to 8 hours which will accelerate the recruitment of potential subjects. In endovascular treatment arm, the time interval between randomization to procedure finish will be controlled within 120 mins. The preparation of endovascular treatment will start immediately after randomization for those eligible patients for IV rt-PA within 4.5 hours after acute stroke onset, with no need to wait for the one-hour rt-PA infusion. A positive trial will suggest substantial clinical benefit from endovascular treatment plus standard medical therapy over standard medical therapy. This trial may provide novel evidence of adopting endovascular treatment for acute patients with BA occlusion, which may consequently advance our current approach for acute stroke treatment.

Official Title
-----------------
Acute Basilar Artery Occlusion: Endovascular Interventions vs Standard Medical Treatment

Conditions
-----------------
Stroke Due to Basilar Artery Occlusion, Acute Cerebrovascular Accidents

Intervention / Treatment
-----------------
* Device: endovascular treatment
* Other: standard medical therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years; Acute ischemic stroke consistent with infarction in the basilar artery territory; Basilar artery occlusion confirmed by CTA/MRA/DSA, within 8 hours of estimated occlusion time; Written informed consent from patient or surrogate, if unable to provide consent. Exclusion Criteria: Computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of Cerebral hemorrhage on presentation; Premorbid mRS ≥ 3 points; Currently in pregnant or lactating; Known serious sensitivity to radiographic contrast agents and nitinol metal; Current participation in another investigation drug or device study; Uncontrolled hypertension defined as systolic blood pressure > 185 mmHg or diastolic blood pressure > 110 mmHg that cannot be controlled except with continuous parenteral antihypertensive medication; Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy with INR >1.7 or institutionally equivalent prothrombin time; Baseline lab values: glucose < 50 mg/dl or > 400 mg/dl, platelets <100*109/L, or Hct<25%; Arterial tortuosity that would prevent the device from reaching the target vessel; Life expectancy less than 1 year; History of major hemorrhage in the past 6 months; Angiographic evidence of significant cerebellar mass effect or acute hydrocephalus. Angiographic evidence of bilateral extended brainstem ischemia.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: standard medical therapy<br>Patients receive standard medical therapy alone. | Other: standard medical therapy<br>* If the patient meets the criteria for IV rt-PA within 4.5 h of stroke onset, he/she will receive a single alteplase dose of 0.9 mg/kg IV(maximum dose: 90mg), with 10% given as a bolus, followed by continuous IV infusion of the other dose within 1h. All patients will receive standard medical therapy. The standard medical therapy conforms with the current American Heart Association/American Stroke Association guidelines.<br>|
| Experimental: endovascular + standard medical therapy<br>Patients receive endovascular treatment plus standard medical therapy. | Device: endovascular treatment<br>* The endovascular treatment is comprised of thrombolysis, mechanical thrombectomy, stenting, or a combination of all these approaches. Generally, Solitaire FR is preferred, other devices such as Trevo or future advanced devices can also be considered which will be decided by the executive committee.<br>Other: standard medical therapy<br>* If the patient meets the criteria for IV rt-PA within 4.5 h of stroke onset, he/she will receive a single alteplase dose of 0.9 mg/kg IV(maximum dose: 90mg), with 10% given as a bolus, followed by continuous IV infusion of the other dose within 1h. All patients will receive standard medical therapy. The standard medical therapy conforms with the current American Heart Association/American Stroke Association guidelines.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Rankin Scale (mRS) | A score of 0-3 will be considered as the favorable outcome. | at 90 days from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mRS score 0-2 |  | at 90 days from randomization | 
| Change of mRS score(shift analysis) |  | at 90 days from randomization | 
| Vessel recanalization rate evaluated by CT angiography or MRA |  | at 24 hours from randomization | 
| PC-ASPECT score on CT/MRI |  | at 24 hours from randomization | 
| GCS score |  | at 24 hours from randomization | 
| NIHSS score |  | at 24 hours from randomization | 
| GCS score |  | at 5-7 days from randomization | 
| NIHSS score |  | at 5-7 days from randomization | 
| EuroQol 5D (EQ-5D) |  | at 90 days from randomization | 
| mortality |  | at 3 months from randomization | 
| symptomatic intracerebral hemorrhage (ICH) |  | within 24 hours from randomization | 
| incidence of non-intracerebral hemorrhage complications |  | at 90 days from randomization | 
| severity of non-intracerebral hemorrhage complications |  | within 90 days from randomization | 
| incidence of nonbleeding severe adverse events (SAEs) |  | within 90 days from randomization | 
| severity of nonbleeding severe adverse events (SAEs) |  | within 90 days from randomization | 
| incidence of procedure and device related complications | i.e., vessel perforation, clinically significant groin complications, dissection, arterial occlusion and embolization, etc. | within 90 days from randomization | 
| severity of procedure and device related complications | i.e., vessel perforation, clinically significant groin complications, dissection, arterial occlusion and embolization, etc. | within 90 days from randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thrombectomy, rt-PA, stroke, endovascular treatment, randomized