Basilar Artery International Cooperation Study

Study Overview
=================
Brief Summary
-----------------
Rationale: Recently our study group reported the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with an acute symptomatic basilar artery occlusion (BAO). Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely. Furthermore, the often-held assumption that intra-arterial thrombolysis (IAT) is superior to intravenous thrombolysis (IVT) in patients with an acute symptomatic BAO is challenged by our data. The BASICS registry was observational and has all the limitations of a non-randomised study. Interpretation of results is hampered by the lack of a standard treatment protocol for all patients who entered the study. Objective: Evaluate the efficacy and safety of IAT in addition to best medical management (BMM) in patients with basilar artery occlusion. Study design: Randomised, multi-centre, open label, controlled phase III, treatment trial. Study population: Patients, aged 18 years and older, with CTA or MRA confirmed basilar occlusion. Intervention: Patients will be randomised between BMM with additional IAT versus BMM alone. IAT has to be initiated within 6 hours from estimated time of BAO. If treated with as part of BMM, IVT should be started within 4.5 hours of estimated time of BAO. Main study parameters/endpoints: Favorable outcome at day 90 defined as a modified Rankin Score (mRS - functional scale) of 0-3.

Official Title
-----------------
Basilar Artery International Cooperation Study

Conditions
-----------------
Basilar Artery Thrombosis, Basilar Artery Embolism, Stroke of Basilar Artery, Stroke, Cerebrovascular Disorders, Basilar Artery Occlusion

Intervention / Treatment
-----------------
* Other: Intra-arterial treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Symptoms and signs compatible with ischemia in the basilar artery territory. Basilar artery occlusion (BAO) confirmed by CTA or MRA. Age 18 years or older (i.e., candidates must have had their 18th birthday). If IVT is considered as part of best medical management, IVT should be started within 4.5 hours of estimated time of BAO. (Estimated time of BAO is defined as time of onset of acute symptoms leading to clinical diagnosis of BAO or if not known last time patient was seen normal prior to onset of these symptoms). Initiation of IAT should be feasible within 6 hours of estimated time of BAO. Exclusion criteria Pre-existing dependency with mRankin ≥3. Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission. Patients who require hemodialysis or peritoneal dialysis. Other serious, advanced, or terminal illness. Any other condition that the investigator feels would pose a significant hazard to the patient if thrombolytic therapy is initiated. Current participation in another research drug treatment protocol (patient cannot start another experimental agent until after 90 days). Informed consent is not or cannot be obtained. Imaging exclusion criteria High-density lesion consistent with hemorrhage of any degree. Significant cerebellar mass effect or acute hydrocephalus. 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 |
| --- | --- |
| No Intervention: Best medical management.<br>Best medical management consists of the standard of care of patients with acute ischemic stroke according to existing local protocols and guidelines, and may include IV thrombolysis. If treated with IVT as part of BMM, IVT should be started within 4.5 hours of estimated time of BAO. | |
| Experimental: Additional intra-arterial treatment.<br>Best medical management followed by intra-arterial treatment and best medical management | Other: Intra-arterial treatment<br>* IA therapy has to be initiated within 6 hours of estimated time of basilar artery occlusion. If an appropriate thrombus or residual stenosis is identified, the choice of IA strategy wil be made by the treating neurointerventionalist. Choice of therapy depends on local approval and experience. If IA thrombolysis is the chosen strategy, a maximum of 22 mg of IA rt-PA or 1.500.000 Units of Urokinase may be given. Stenting is allowed in the presence of a high-grade vertebral artery stenosis or occlusion hampering adequate endovascular access to the basilar artery and in case of a residual high-grade basilar artery stenosis. The use of any other treatment strategy depends on local approval and experience, and is only allowed after prior approval of the steering committee.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Favourable outcome | Favourable outcome at day 90 defined as a modified Rankin Score (mRS - functional scale) of 0-3. | day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Excellent outcome | Excellent outcome at day 90 defined as a modified Rankin Score (mRS - functional scale) of 0-2. | day 90 | 
| Modified Rankin Score | Modified Rankin Score - not dichotomized. | day 90 | 
| NIHSS | National Institutes of Health Stroke Scale (NIHSS - acute assessment scale) at timepoints: directly pre intravenous thrombolysis directly pre randomization (post intravenous thrombolysis) at 24 hours +- 6 hours post treatment. | pre IVT, pre randomization, 24h post treatment | 
| EQ-5D | EQ-5D (quality of life) at day 90 and at 12 months. | day 90 and 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
basilar, stroke, mechanical, thrombolysis, intra-arterial, trombectomy