Trial on Endovascular Aneurysm Management (TEAM)

• To better define the natural history of unruptured aneurysms eligible for endovascular treatment. [ Time Frame: At 5 and 10 years ] [ Designated as safety issue: No ]
• To define the rate of hemorrhagic events despite endovascular treatment. [ Time Frame: At 1, 5 and 10 years ] [ Designated as safety issue: Yes ]
• To determine the Morbidity/Mortality (M/M) related to endovascular treatment of unruptured aneurysms. [ Time Frame: At 1, 5 and 10 years ] [ Designated as safety issue: Yes ]
• To compare overall M/M of the 2 groups [ Time Frame: At 10 years ] [ Designated as safety issue: Yes ]
• To compare the quality of life and anxiety levels of surviving patients of the 2 groups. [ Time Frame: At 5 and 10 years ] [ Designated as safety issue: No ]
• To determine the rate of occlusion of aneurysms treated by coiling in an effort to estimate longer-term efficacy. [ Time Frame: At 5 and 10 years ] [ Designated as safety issue: No ]
• To determine the rate of aneurysmal growth in the conservative group in surviving patients. [ Time Frame: At 5 and 10 years ] [ Designated as safety issue: No ]
• To verify cognitive functions using the MoCA in all patients as well as by detailed neuropsychological testing, before and 6 months after treatment in a consecutive sample of 100 patients of both groups. [ Time Frame: Baseline, 1 year, 5 and 10 years ] [ Designated as safety issue: No ]

• To better define the natural history of unruptured aneurysms eligible for endovascular treatment [ Time Frame: At 5 and 10 years ]
• To define the rate of hemorrhagic events despite endovascular treatment. [ Time Frame: At 1, 5 and 10 years ]
• To determine the Morbidity/Mortality (M/M) related to endovascular treatment of unruptured aneurysms. [ Time Frame: At 1, 5 and 10 years ]
• To compare overall M/M of the 2 groups [ Time Frame: At 10 years ]
• To compare the quality of life and anxiety levels of surviving patients of the 2 groups [ Time Frame: At 5 and 10 years ]
• To determine the rate of occlusion of aneurysms treated by coiling in an effort to estimate longer-term efficacy. [ Time Frame: At 5 and 10 years ]
• To determine the rate of aneurysmal growth in the conservative group in surviving patients [ Time Frame: At 5 and 10 years ]
• To verify cognitive functions using the MoCA in all patients as well as by detailed neuropsychological testing, before and 6 months after treatment in a consecutive sample of 100 patients of both groups. [ Time Frame: Baseline, 1 year, 5 and 10 years ]

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.

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.

• Device: Embolization, coiling
  Endovascular embolization with platinum coils
  Other Name: Standard and bioactive coils
• Other: Conservative management
  watchful observation until indication for treatment arises

• No Intervention: 1
  Conservative management (watchful observation)
  Intervention: Other: Conservative management
• Active Comparator: 2
  Endovascular treatment
  Intervention: Device: Embolization, coiling

• Raymond J, Meder JF, Molyneux AJ, Fox AJ, Johnston SC, Collet JP, Rouleau I; Trial on Endovascular Aneurysm Management (TEAM) collaborative group. Trial on endovascular treatment of unruptured aneurysms (TEAM): study monitoring and rationale for trial interruption or continuation. J Neuroradiol. 2007 Mar;34(1):33-41. Review.
• Raymond J, Meder JF, Molyneux AJ, Fox AJ, Johnston SC, Collet JP, Rouleau I; The Trial On Endovascular Aneurysm Management Team Collaborative Group. Unruptured intracranial aneurysms: the unreliability of clinical judgment, the necessity for evidence, and reasons to participate in a randomized trial. J Neuroradiol. 2006 Oct;33(4):211-9. Review. No abstract available.
• Raymond J, Guilbert F, Weill A, Roy D. Unruptured intracranial aneurysms: a call for a randomized clinical trial. AJNR Am J Neuroradiol. 2006 Feb;27(2):242-3. No abstract available.
• Raymond J, Guilbert F, Weill A, Georganos SA, Juravsky L, Lambert A, Lamoureux J, Chagnon M, Roy D. Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke. 2003 Jun;34(6):1398-403. Epub 2003 May 29.
• Raymond J, Chagnon M, Collet JP, Guilbert F, Weill A, Roy D. A randomized trial on the safety and efficacy of endovascular treatment of unruptured intracranial aneurysms is feasible. Interv Neuroradiol. 2004. Jun;10(2):103-112.
• Raymond J, Molyneux AJ, Fox AJ, Johnston SC, Collet JP, Rouleau I; the TEAM collaborative group. The TEAM trial: Safety and efficacy of endovascular treatment of unruptured intracranial aneurysms in the prevention of aneurysmal hemorrhages: A randomized comparison with indefinite deferral of treatment in 2002 patients followed for 10 years. Trials. 2008 Jul 16;9(1):43.
• Naggara O, Raymond J, Guilbert F, Roy D, Weill A, Altman DG. Analysis by categorizing or dichotomizing continuous variables is inadvisable: an example from the natural history of unruptured aneurysms. AJNR Am J Neuroradiol. 2011 Mar;32(3):437-40. Epub 2011 Feb 17.
• Raymond J. Incidental intracranial aneurysms: rationale for treatment. Curr Opin Neurol. 2009 Feb;22(1):96-102.

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