Basilar Artery International Cooperation Study Trial.

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. 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 IAT is superior to 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 additional IA therapy after IV thrombolysis in patients with acute basilar artery occlusion.



Study design:

Randomised, multi-centre, open label, controlled phase III, treatment trial.



Study population:

Patients treated with IV thrombolysis and CTA or MRA confirmed basilar occlusion aged 18 through 85 years.



Intervention:

Patients will be randomised between additional IA therapy followed by maximum supportive care versus maximum supportive care alone.
IVT has to be initiated within 4.5 hours from estimated time of basilar artery occlusion and IA therapy within 6 hours.



Main study parameters/endpoints:

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



Nature and extend of the burden and risks associated with participation, benifit and group relatedness:

Although, to date, no data from a randomised controlled trial support the use of IAT for BAO, IAT was by far the most commonly used treatment type in the BASICS registry. The use of additional IAT after standard IVT is supported by the results of trials performed with patients with occlusions in other vascular territories. Patients randomised into the additional IAT group will undergo intra-arterial catheterization and intra-arterial therapy will be initiated if indicated. Effective amount of radiation during this 1-2 hour procedure will be about 20 mSv. Main risks for catheterization and IAT comprise local and intracranial haemorrhage. In the BASICS registry we reported a risk for symptomatic intracranial haemorrhage of 14% in patients treated with IAT versus 6% in patients treated with IVT. Follow-up telephone surveys at 1 and 12 months and blinded exam at 3 months will take up to 50 minutes in total.



Recruiting countries: Australia, Brazil, Canada, Czech Republic, Germany, Israel, Italy, The Netherlands, Spain, Switserland, United Kingdom, United States.

The null hypothesis for this study is that additional intra-arterial treatment after intravenous thrombolysis in patients with a acute basilar artery occlusion leads to similar distribution of functional outcomes as intravenous thrombolysis alone.

N/A

IV rt-PA:

All patients are treated with a standard full dose of open-label IV rt-PA (0.9mg/kg; 90mg
maximum) if standard eligibility criteria are met. Patients treated with IVT within 4.5 hours
of symptom onset, and those who are treated beyond 4.5 hours of symptom onset but
within 4.5 hours of estimated time of basilar artery occlusion will be regarded as two prespecified
subgroups for secondary analysis. In patients treated beyond 4.5 hours of
symptom onset, informed consent needs to be obtained prior to initiation of IVT.



IA therapy:

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 will
be made by the treating neurointerventionalist. IA treatment options available will be any
of the following devices or thrombolytics, depending on local approval and experience;
the Concentric Merci® thrombus-removal device, Penumbra, Solitaire, infusion of rt-PA
combined with an application of low-intensity ultrasound at the site of the occlusion via
the EKOS® Micro-Infusion Catheter, infusion of alteplase or urokinase via a standard
micro-catheter. 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.

The IA approach is aimed at recanalization of the basilar artery. In order to ensure
optimal perfusion one posterior cerebral artery should be patent. In the presence of
residual occlusions of branches of the basilar artery after complete recanalization of the
basilar artery the use of additional thrombolytic therapy should be kept to a minimum due
to the limited potential gain.
Clinical improvement could be a reason not to initiate IA therapy despite the presence of
persistent basilar artery occlusion on conventional angiography. The initiation of IA
therapy after identification of an appropriate thrombus in the basilar artery or high grade
residual stenosis considered to have been the cause of occlusion on conventional
angiography will be left to the judgment of the treating physician.