BASICS: Basilar Artery International Cooperation Study

Sponsor

Erik van der Hoeven (Other)

Overall Status

Unknown status

CT.gov ID

NCT01717755

Collaborator

BASICS Study Group (Other)

282

Enrollment

Locations

Arms

Duration (Months)

10.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Basilar Artery Thrombosis Basilar Artery Embolism Stroke of Basilar Artery Stroke Cerebrovascular Disorders Basilar Artery Occlusion	Other: Intra-arterial treatment	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

282 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Basilar Artery International Cooperation Study

Study Start Date :

Oct 1, 2011

Anticipated Primary Completion Date :

Jan 1, 2019

Anticipated Study Completion Date :

Jan 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Best medical management. 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. Best medical management followed by intra-arterial treatment and best medical management	Other: Intra-arterial treatment 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.

Arm

Intervention/Treatment

No Intervention: Best medical management.

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.

Best medical management followed by intra-arterial treatment and best medical management

Other: Intra-arterial treatment

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.

Outcome Measures

Primary Outcome Measures

Favourable outcome [day 90]
Favourable outcome at day 90 defined as a modified Rankin Score (mRS - functional scale) of 0-3.

Secondary Outcome Measures

Excellent outcome [day 90]
Excellent outcome at day 90 defined as a modified Rankin Score (mRS - functional scale) of 0-2.
Modified Rankin Score [day 90]
Modified Rankin Score - not dichotomized.
NIHSS [pre IVT, pre randomization, 24h post treatment]
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.
EQ-5D [day 90 and 12 months]
EQ-5D (quality of life) at day 90 and at 12 months.

Other Outcome Measures

Recanalization [24 hours ± 6 hours]
Recanalization at 24 hours ± 6 hours, by CT angiography.
Volume of cerebral infarction [24 hours ± 6 hours]
Volume of cerebral infarction on NCCT and CTA source images.
SICH [24 hours ± 6 hours.]
Symptomatic intracranial hemorrhage at 24 hours CT imaging ± 6 hours.
Mortality [90 days]
Mortality at 90 days.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fortaleza General Hospital	Fortaleza		Brazil
2	Hospital das Clinicas de Ribeirao Preto	Ribeirão Preto		Brazil
3	Klinikum Augsburg	Augsburg		Germany
4	Berlin Charite Hospital	Berlin		Germany
5	Dresden University Hospital	Dresden		Germany
6	University Medical Center Mannheim	Mannheim		Germany
7	Oberschwabenklinik	Ravensburg		Germany
8	Bergamo Hospital	Bergamo		Italy
9	Genova Hospital	Genua		Italy
10	University Hospital Modena	Modena		Italy	41100
11	Santa Corona Hospital	Pietra Ligure		Italy
12	Roma Umberto I	Rome		Italy
13	Varese Hospital	Varese		Italy
14	Rijnstate	Arnhem	Gelderland	Netherlands	6800 TA
15	Academic Hospital Maastricht	Maastricht	Limburg	Netherlands	6229 HX
16	St. Elisabeth Hospital	Tilburg	Noord Brabant	Netherlands	5022 GC
17	Academic Medical Center	Amsterdam	Noord-Holland	Netherlands	1105AZ
18	St. Antonius Hospital	Nieuwegein	Utrecht	Netherlands	3430 EM
19	MCH Westeinde	The Hague	Zuid-Holland	Netherlands	2512 VA
20	University Medical Center Groningen	Groningen		Netherlands
21	Leiden University Hospital	Leiden		Netherlands
22	Erasmus Medical Center	Rotterdam		Netherlands
23	Haga Hospital	The Hague		Netherlands
24	Universitary Medical Center Utrecht	Utrecht		Netherlands	3584 CX
25	University Hospital North Norway	Tromso		Norway
26	St. Olavs Hospital Trondheim	Trondheim		Norway
27	University Hospital of Lausanne	Lausanne	Vaud	Switzerland	CH-1011