Flow Diversion in Intracranial Aneurysm Treatment

Background:

Intracranial aneurysms, particularly large/giant, fusiform or recurrent aneurysms are increasingly treated with flow diverters (FDs), a recently introduced and approved neurovascular device. While some rare cases may not be treated any other way, in most patients a more conventional, conservative, or validated approach such as coiling, parent vessel occlusion, or surgical clipping exists. Early series and registries of the use of FDs in various types of aneurysms have reported treatment-related morbidity and mortality ranging from 0 to 4 and 8% respectively, most often from delayed haemorrhage. Hence, although there is growing enthusiasm to use these powerful new tools, complications are increasingly reported.

Rationale and Hypothesis:

There is an urgent need to offer the new tool afforded by FDs to patients currently presenting with a difficult aneurysm, in a context that can offer protection from over-optimistic perspectives, fashion, learning curves and marketing. Only a randomized clinical trial can offer such protection as well as provide an answer to the question of which treatment option leads to better patient outcomes. The primary hypothesis is that flow diversion can be performed with an "acceptable" immediate complication rate, defined as less than 15% morbidity and mortality (modified Rankin Score > 2 at 3 months), AND increase the number of patients experiencing successful therapy, defined as complete or near complete occlusion of the aneurysm from 75 to 90%.

Objectives:

Compare flow diversion (FD) to Best-Standard Treatment (BST) in the context of an RCT. BST may be any of the following: 1) conservative management; 2) coiling with or without high porosity stenting; 3) parent vessel occlusion with or without bypass; 4) surgical clipping; 5) enter a registry for FD, when the only treatment alternative is FD for compassionate use.

Methods:

Following randomization to FD or BST, patients will undergo the assigned intervention and be followed for 12 months. Clinical status will be recorded at discharge, at 1-3 months, and at 3-12 months. Angiographic evaluation will be recorded at 3-12 months. Adverse Events will be recorded immediately after the procedure and during the 12-month follow-up period. Patients in the FD registry will similarly be followed for 12 months. A total of 344 patients will be recruited in 20 centers worldwide. The trial is expected to last for 5 years.

Analysis:

Comparability between FD and BST groups will use descriptive statistics or frequency tables, independent ANOVAs or Mantel-Haentzel and chi-square tests. Comparison of primary outcome will use a z-test for independent proportions at 12 months. Safety data will be compared through independent t-tests or chi-square statistics. Logistic regression will be used to find variables capable of predicting success in both groups at 12 months.

Inclusion criteria

• Any patient with a "difficult" intracranial aneurysm in whom flow diversion is considered an appropriate if not the best but yet unproved therapeutic option by the participating clinician. Current indications may be (but not restricted to) symptomatic large or giant cavernous carotid, ophthalmic and vertebral aneurysms, fusiform intradural aneurysms, or recurring, persistent lesions after previous coiling. Aneurysm may be a recent rupture, although risks associated with antiplatelet regimens in this context should make this option rarely used

Exclusion criteria

• Severe allergy, intolerance or bleeding disorder that prohibit the use of ASA or clopidogrel.
• Absolute contraindication to endovascular treatment or anesthesia.
• Patients unable to give informed consent.