Trial on Endovascular Aneurysm Management

Study Overview
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Brief Summary
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The management of patients with unruptured aneurysms is controversial. Patients with unruptured aneurysms may suffer intracranial hemorrhage, but the incidence of this event is still debated. Endovascular treatment can prevent rupture, but involves immediate risks; furthermore, successful treatment does not eliminate all risks. A randomized trial may be the best way to demonstrate the potential benefits of endovascular over conservative management of unruptured aneurysms.

Detailed Description
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This study is designed as a pragmatic trial. All candidates for endovascular treatment of one or more unruptured intracranial aneurysms will be offered to participate. Unruptured aneurysms may be recently discovered or prevalent. If they accept, subjects will be randomized to one of the two arms of the trial: Conservative management (Observation) or Endovascular treatment. Both groups will be advised to obtain medical treatment for hypertension if necessary and will receive counselling for behavioural risk factor modelling (smoking or excessive drinking) when indicated. A non-invasive (MRA or CTA) or catheter angiogram and a baseline CT-scan or MRI of the brain are required to enter the study. These studies should demonstrate the unequivocal presence of a saccular aneurysm >=3 mm treatable by endovascular methods. A catheter angiogram is required if there is doubt. Imaging studies will be reviewed centrally. Both treatments will be standardized. Patients will be followed similarly for a minimum of 10 years.

Official Title
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Safety and Efficacy of Endovascular Treatment of Unruptured Intracranial Aneurysms in the Prevention of Aneurysmal Haemorrhages: A Randomized Comparison With Indefinite Deferral of Treatment in 2002 Patients Followed for 10 Years

Conditions
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Brain Aneurysm

Intervention / Treatment
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* Device: Embolization, coiling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least one documented subarachnoid aneurysm, never ruptured Patient aged 18 or older Life expectancy more than 10 years Exclusion Criteria: Patients with recent (less than 3 months) intracranial haemorrhage Lesion characteristics unsuitable for endovascular treatment Patients with a single extradural aneurysm Aneurysms < 3 mm or giant aneurysms (≥ 25 mm) Patients with a poor outcome (Rankin scale ≥ 3) after the rupture, surgical or endovascular treatment of another aneurysm Patients with incompletely treated aneurysms that have previously ruptured Patients with associated arteriovenous malformations Patients with new severe progressive symptoms in relationship with the aneurysm (sudden onset, severe persisting headaches suggestive of impending rupture, third-nerve palsy, mass-effect) Patients with previous intracranial haemorrhage from unknown etiology Patients with multiple unruptured aneurysms in whom surgical clipping of one or many aneurysms is planned in addition to endovascular management Patients with absolute contraindications to anaesthesia, endovascular treatment, or administration of contrast material, including low-osmolarity agents or gadolinium Pregnant patients Patients unable to give informed consent

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conservative<br>Conservative management (watchful observation) | |
| Active Comparator: Endovascular<br>Endovascular treatment | Device: Embolization, coiling<br>* Endovascular embolization with platinum coils<br>* Other names: Standard and bioactive coils;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Disease or Treatment-related Morbidity and Mortality. | Morbidity or mortality is evaluated using the modified Rankin Scale (mRS) which goes from 0 to 6, with 0 for no symptoms at all, and 6 for Mortality. The scores were attributed using a structured interview process. a Good Primary Outcome was categorized from mRS scores of 0, 1, or 2. a Bad Primary Outcome was categorized from mRS scores of 3, 4, 5 or 6. | 1 year after treatment or observation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Hemorrhage in Conservative Group | To better define the natural history of unruptured aneurysms eligible for endovascular treatment. | At 5 and 10 years | 
| Number of Participants With Hemorrhage in Endovascular Group | Number of participants experiencing a hemorrhagic event despite successful treatment. This outcome measure gives an estimate of risk of rupture despite treatment | At 1 year | 
| Number of Participants in Each Score of the Modified Rankin Scale in Endovascular Group | The modified Rankin Scale (mRS) goes from 0 to 6, with 0 for no symptoms at all, and 6 for Mortality. The scores were attributed using a structured interview process. The number of participants having in each score is given. | At 1 year | 
| Modified Rankin Score | To compare overall Morbidity/Mortality of the 2 groups | At 10 years | 
| Measures on 36-Item Short-Form Health Survey (SF-36) | To compare the quality of life and anxiety levels of surviving patients of the 2 groups according to the SF-36 questionnaire minimum is 0 (maximum disability) maximum is 100 (No disability) | At 5 and 10 years | 
| Occlusion State in the Endovascular Group | To determine the rate of occlusion of aneurysms treated by coiling in an effort to estimate longer-term efficacy. | At 5 and 10 years | 
| Occlusion State of the Aneurysm in the Conservative Group | To determine the rate of aneurysmal growth in the conservative group in surviving patients. | At 5 and 10 years | 
| Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | To verify cognitive functions using the MoCA in all patients before and 6 months after treatment in a consecutive sample of 100 patients of both groups. Minimum value on the MoCA is 0 (maximum cognitive decline) Maximum value on the MoCA is 30 (no cognitive decline) A score higher than 26 was categorized as good cognitive condition A score of 26 or lower was categorized as bad cognitive conditionn | Baseline, 1 year, 5 and 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aneurysm, Brain, Unruptured, observation, treatment, Endovascular