Brain Aneurysm
Conditions
Keywords
Aneurysm, Brain, Unruptured, observation, treatment, Endovascular
Brief summary
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
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.
Interventions
DEVICEEmbolization, coiling
Endovascular embolization with platinum coils
Sponsors
Canadian Institutes of Health Research (CIHR)
Centre hospitalier de l'Université de Montréal (CHUM)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Disease or Treatment-related Morbidity and Mortality. | 1 year after treatment or observation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hemorrhage in Endovascular Group | At 1 year | Number of participants experiencing a hemorrhagic event despite successful treatment. This outcome measure gives an estimate of risk of rupture despite treatment |
| Number of Participants in Each Score of the Modified Rankin Scale in Endovascular Group | At 1 year | 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. |
| Modified Rankin Score | At 10 years | To compare overall Morbidity/Mortality of the 2 groups |
| Rate of Hemorrhage in Conservative Group | At 5 and 10 years | To better define the natural history of unruptured aneurysms eligible for endovascular treatment. |
| Occlusion State in the Endovascular Group | At 5 and 10 years | To determine the rate of occlusion of aneurysms treated by coiling in an effort to estimate longer-term efficacy. |
| Occlusion State of the Aneurysm in the Conservative Group | At 5 and 10 years | To determine the rate of aneurysmal growth in the conservative group in surviving patients. |
| Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | Baseline, 1 year, 5 and 10 years | 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 |
| Measures on 36-Item Short-Form Health Survey (SF-36) | At 5 and 10 years | 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) |
Countries
Canada, France, United Kingdom, United States
Participant flow
Recruitment details
Participants are recruited when seen in clinic either for neurological symptoms or when aneurysm is an incidental finding
Pre-assignment details
there are no pre-assignment procedures before assignment to groups
Participants by arm
| Arm | Count |
|---|---|
| Conservative Conservative management (watchful observation)
Inclusion criteria:
1. At least one documented subarachnoid aneurysm, never ruptured
2. Patient aged 18 or older
3. Life expectancy more than 10 years
Exclusion crieria:
1. Patients with recent (less than 3 months) intracranial haemorrhage
2. Lesion characteristics unsuitable for endovascular treatment
3. Patients with a single extradural aneurysm
4. Aneurysms \<3mm or giant aneurysms (≥25mm)
5. Patients with a poor outcome (Rankin scale ≥3) after the rupture, surgical or endovascular treatment of another aneurysm
6. Patients with incompletely treated aneurysms that have previously ruptured
7. Patients with associated arteriovenous malformations
8. 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)
9. Patients with previous intracranial haemorrhage from unknown aetiology
10. Patients with multiple unruptured aneurysms in whom surgical clipping of one or many aneurysms is planned in addition to endovascular management
11. Patients with absolute contraindications to anaesthesia, endovascular treatment, or administration of contrast material, including low-osmolarity agents or gadolinium
12. Pregnant patients
13. Patients unable to give informed consent | 38 |
| Endovascular Endovascular treatment
Embolization, coiling: Endovascular embolization with platinum coils
Same population as Conservative management | 42 |
| Total | 80 |
Baseline characteristics
| Characteristic | Conservative | Endovascular | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 10 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 32 Participants | 63 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Canada | 11 participants | 20 participants | 31 participants |
| Region of Enrollment France | 11 participants | 10 participants | 21 participants |
| Region of Enrollment Poland | 4 participants | 2 participants | 6 participants |
| Region of Enrollment United Kingdom | 9 participants | 9 participants | 18 participants |
| Region of Enrollment United States | 3 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 27 Participants | 25 Participants | 52 Participants |
| Sex: Female, Male Male | 11 Participants | 17 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 42 |
| other Total, other adverse events | 2 / 38 | 3 / 42 |
| serious Total, serious adverse events | 0 / 38 | 1 / 42 |
Outcome results
Primary
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.
Time frame: 1 year after treatment or observation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conservative | Number of Participants With Disease or Treatment-related Morbidity and Mortality. | 0 Participants |
| Endovascular | Number of Participants With Disease or Treatment-related Morbidity and Mortality. | 0 Participants |
Secondary
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)
Time frame: At 5 and 10 years
Population: No patients available for outcome measure at 5 and 10 years because study was terminated
Secondary
Modified Rankin Score
To compare overall Morbidity/Mortality of the 2 groups
Time frame: At 10 years
Population: No patients available for outcome measure at 10 years because study was terminated
Secondary
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.
Time frame: At 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Conservative | Number of Participants in Each Score of the Modified Rankin Scale in Endovascular Group | mRS is 0 | 10 Participants |
| Conservative | Number of Participants in Each Score of the Modified Rankin Scale in Endovascular Group | mRS is 1 | 2 Participants |
| Conservative | Number of Participants in Each Score of the Modified Rankin Scale in Endovascular Group | mRS is 2 | 0 Participants |
| Endovascular | Number of Participants in Each Score of the Modified Rankin Scale in Endovascular Group | mRS is 0 | 8 Participants |
| Endovascular | Number of Participants in Each Score of the Modified Rankin Scale in Endovascular Group | mRS is 1 | 2 Participants |
| Endovascular | Number of Participants in Each Score of the Modified Rankin Scale in Endovascular Group | mRS is 2 | 1 Participants |
Secondary
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
Time frame: Baseline, 1 year, 5 and 10 years
Population: Patients with MoCa scores at Baseline and 1 year
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Conservative | Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | Baseline | Score is 26 or lower | 1 Participants |
| Conservative | Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | Baseline | Score is higher than 26 | 10 Participants |
| Conservative | Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | 1 year | Score is 26 or lower | 3 Participants |
| Conservative | Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | 1 year | Score is higher than 26 | 8 Participants |
| Endovascular | Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | 1 year | Score is higher than 26 | 7 Participants |
| Endovascular | Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | Baseline | Score is 26 or lower | 4 Participants |
| Endovascular | Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | 1 year | Score is 26 or lower | 2 Participants |
| Endovascular | Number of Participants With a Bad Cognitive Function Evaluated According to the Montreal Cognitive Assessment Scale (MoCA) | Baseline | Score is higher than 26 | 5 Participants |
Secondary
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
Time frame: At 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conservative | Number of Participants With Hemorrhage in Endovascular Group | 0 Participants |
| Endovascular | Number of Participants With Hemorrhage in Endovascular Group | 0 Participants |
Secondary
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.
Time frame: At 5 and 10 years
Population: No patients available for outcome measure at 5 years because study was terminated
Secondary
Occlusion State of the Aneurysm in the Conservative Group
To determine the rate of aneurysmal growth in the conservative group in surviving patients.
Time frame: At 5 and 10 years
Population: No patients available for outcome measure at 5 years because study was terminated
Secondary
Rate of Hemorrhage in Conservative Group
To better define the natural history of unruptured aneurysms eligible for endovascular treatment.
Time frame: At 5 and 10 years
Population: No patients available for outcome measure at 5 years because study was terminated