Flow Diversion in Intracranial Aneurysm Treatment

Study Overview
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Brief Summary
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Flow diverters are a recent addition to the range of endovascular devices now available for the treatment of intracranial aneurysms. The FIAT trial aims at comparing flow diversion to best standard treatment in the context of a randomised controlled trial. Best standard treatment may include any of the following and will be left to the treating physician to decide : 1) conservative management; 2) coiling with or without high porosity stenting; 3) parent vessel occlusion with or without bypass; 4) surgical clipping. If the only treatment alternative is deemed to be flow diversion for compassionate use, then randomisation will not be carried out, but patient will enter a registry and her data recorded according to same schedule as randomised patients. The primary hypothesis is that flow diversion can be performed with an acceptable immediate complication rate, defined as less than 15% morbidity and mortality, AND increase the number of patients experiencing successful therapy, defined as complete or near complete occlusion of the aneurysm from 75 to 90%, relative to best standard treatment.

Detailed Description
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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.

Official Title
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A Randomized Trial Comparing Flow Diversion and Best-standard Treatment - the FIAT Trial

Conditions
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Intracranial Aneurysm

Intervention / Treatment
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* Procedure: flow diversion
* Other: conservative management
* Procedure: endovascular coiling
* Procedure: balloon parent vessel occlusion
* Procedure: surgical clipping


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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: flow diversion<br>Flow diverters are low porosity braided endovascular stent devices. They can be used with or without coiling. | Procedure: flow diversion<br>* endovascular treatment with flow diversion including standard management of thrombo-embolic risk<br>|
| Active Comparator: Best standard treatment<br>Best standard treatment can by any of the standard management options: coiling, stenting plus coiling, surgical clipping, parent vessel occlusion, observation | Other: conservative management<br>* conservative management is watchful observation of the aneurysm until indication for intervention arises<br>Procedure: endovascular coiling<br>* standard endovascular coiling of aneurysm with any type of already approved coil. High porosity stents may be used as an adjunct technique to coiling<br>Procedure: balloon parent vessel occlusion<br>* sacrifice of parent artery of aneurysm by endovascular balloon occlusion with or without bypass<br>Procedure: surgical clipping<br>* clipping of the aneurysm following invasive brain surgery<br>|
| Other: Registry for flow diversion<br>Flow diversion when randomization between flow diversion and best standard treatment is not possible and the only alternative is flow diversion for compassionate use. In this case there will be no random allocation but the patient will be entered into a registry | Procedure: flow diversion<br>* endovascular treatment with flow diversion including standard management of thrombo-embolic risk<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of success of therapy | Rate of success increases from 75% to 90%, with success defined as complete or near complete occlusion of the aneurysm combined with a modified Rankin score of less or equal to 2. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Rankin score | modified Rankin score at discharge, and at 3 and 12 months post-treatment (last observation carried forward) | discharge, 3 and 12 months | 
| rate of peri-operative complications | rate of ischemic strokes and intracranial hemorrhages during the peri-operative period | 30 days | 
| rate of Adverse Events | rate of new stroke, neurological symptom or sign during follow-up | 12 months | 
| angiographic outcome | degree of occlusion of aneurysm as assessed by invasive or non-invasive imaging (last observation carried forward | 12 months | 
| rate of retreatment of index aneurysm | rate of retreatment of index aneurysm due residual aneurysm after initial treatment | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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flow diversion, endovascular treatment, symptomatic aneurysm, cavernous carotid aneurysm, ophthalmic aneurysm, vertebral aneurysm