Brief Summary
The purpose of this study is to compare the clinical outcome of surgical clipping and endovascular coiling for ruptured intracranial aneurysms not included in the original ISAT Study.
Brief Title
International Subarachnoid Aneurysm Trial II
Detailed Description
The International Subarachnoid Aneurysm Trial (ISAT) was a turning point in modern neurosurgical history (1). The trial showed that for 2143 subarachnoid hemorrhage (SAH)patients eligible for both surgery and endovascular coiling, randomized allocation to coiling was associated with better one year clinical outcomes, defined as survival without dependency (absolute risk reduction (ARR) of 7.4% (95%CI; 3.6 - 11.2, p=0.0001). Because ISAT was a positive pragmatic trial, the interpretation of the trial results was that coiling should be adopted as the first-line treatment for ruptured lesions, for patients with the types of aneurysms included in ISAT, of which the great majority were small (≥10 mm) anterior circulation aneurysms.
Although ISAT was well-designed, conducted, and reported, trial results were not always properly interpreted, and endovascular coiling was perhaps inappropriately extrapolated beyond what ISAT demonstrated. Endovascular treatment for ruptured aneurysms has now become first-line treatment in many centers (2), which may be appropriate for small, anterior circulation lesions, but there is no evidence to support this practice for the wide spectrum of non-ISAT patients and aneurysms. A recent pre-randomized study of coiling as first-intention (3)showed better results for those ruptured aneurysms felt to be readily coilable; however, the optimal management of more difficult-to-coil ruptured aneurysms remains unclear.
Further compounding the problem are the concerns that aneurysm coiling may not be as durable in the long-term as surgical clipping, leading many neurosurgeons to continue to clip most ruptured aneurysms in spite of ISAT results.
Proponents of endovascular treatment sometimes justify this extrapolation of ISAT results on the basis of improved catheter and coil technology, although this has never been demonstrated. However, the addition of stents and flow-diverters, which were not tested in ISAT, may increase endovascular treatment risks, especially when combined with dual anti-platelet agents. The introduction of these devices allowed for the expansion of indications of EVT to include wide-necked aneurysms, lesions which would not have been included in ISAT. The wider spectrum of patients and aneurysms now considered for EVT may not all experience the same degree of benefit as seen in the original ISAT trial (4). Considering the relatively small ARR of 7.4% favouring coiling, when the additional risks due to stents are included, the balance may have tipped to favour surgical clipping.
These new questions deserve formal study in the context of a randomized clinical trial.
Although ISAT was well-designed, conducted, and reported, trial results were not always properly interpreted, and endovascular coiling was perhaps inappropriately extrapolated beyond what ISAT demonstrated. Endovascular treatment for ruptured aneurysms has now become first-line treatment in many centers (2), which may be appropriate for small, anterior circulation lesions, but there is no evidence to support this practice for the wide spectrum of non-ISAT patients and aneurysms. A recent pre-randomized study of coiling as first-intention (3)showed better results for those ruptured aneurysms felt to be readily coilable; however, the optimal management of more difficult-to-coil ruptured aneurysms remains unclear.
Further compounding the problem are the concerns that aneurysm coiling may not be as durable in the long-term as surgical clipping, leading many neurosurgeons to continue to clip most ruptured aneurysms in spite of ISAT results.
Proponents of endovascular treatment sometimes justify this extrapolation of ISAT results on the basis of improved catheter and coil technology, although this has never been demonstrated. However, the addition of stents and flow-diverters, which were not tested in ISAT, may increase endovascular treatment risks, especially when combined with dual anti-platelet agents. The introduction of these devices allowed for the expansion of indications of EVT to include wide-necked aneurysms, lesions which would not have been included in ISAT. The wider spectrum of patients and aneurysms now considered for EVT may not all experience the same degree of benefit as seen in the original ISAT trial (4). Considering the relatively small ARR of 7.4% favouring coiling, when the additional risks due to stents are included, the balance may have tipped to favour surgical clipping.
These new questions deserve formal study in the context of a randomized clinical trial.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Intracranial Hemorrhage Ruptured Aneurysm
Eligibility Criteria
Inclusion Criteria:
* Patients at least 18 years of age
* At least one documented, intradural, intracranial aneurysm, ruptured within last 30 days
* SAH WFNS grade 4 or less
* The patient and aneurysm are considered appropriate for either surgical or endovascular treatment by the treating team
Exclusion Criteria:
* Patients with absolute contraindications administration of contrast material (any type)
* Patients with AVM-associated aneurysms
* Aneurysm located at basilar apex
* Patients at least 18 years of age
* At least one documented, intradural, intracranial aneurysm, ruptured within last 30 days
* SAH WFNS grade 4 or less
* The patient and aneurysm are considered appropriate for either surgical or endovascular treatment by the treating team
Exclusion Criteria:
* Patients with absolute contraindications administration of contrast material (any type)
* Patients with AVM-associated aneurysms
* Aneurysm located at basilar apex
Inclusion Criteria
Inclusion Criteria:
* Patients at least 18 years of age
* At least one documented, intradural, intracranial aneurysm, ruptured within last 30 days
* SAH WFNS grade 4 or less
* The patient and aneurysm are considered appropriate for either surgical or endovascular treatment by the treating team
* Patients at least 18 years of age
* At least one documented, intradural, intracranial aneurysm, ruptured within last 30 days
* SAH WFNS grade 4 or less
* The patient and aneurysm are considered appropriate for either surgical or endovascular treatment by the treating team
Gender
All
Gender Based
false
Keywords
Aneurysm
Intracranial Aneurysm
Vascular Diseases
Cardiovascular Diseases
Intracranial Arterial Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01668563
Org Class
Other
Org Full Name
Centre hospitalier de l'Université de Montréal (CHUM)
Org Study Id
CE 12.136
Overall Status
Active, not recruiting
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
International Subarachnoid Aneurysm Trial II Comparing Clinical Outcomes of Surgical Clipping and Endovascular Coiling for Ruptured Intracranial Aneurysms Not Included in the Original ISAT Study.
Primary Outcomes
Outcome Description
Number of patients experiencing a poor clinical outcome at one year post-treatment, defined as a modified Rankin Scale (mRS) score of \>2.
Outcome Measure
poor clinical outcome(mRS>2)
Outcome Time Frame
12 months
Secondary Outcomes
Outcome Description
An intracranial hemorrhage will be judged from cross-sectional imaging (CT or MRI), from a positive lumbar puncture in the setting of an acute headache, or following sudden death preceded by an acute headache.
Outcome Time Frame
one year
Outcome Measure
Occurrence of an intracranial hemorrhage following treatment
Outcome Description
In situations where treatment is initiated but terminated without a proper test of that treatment modality, such as in the event of anaesthetic difficulty requiring the intended treatment to be delayed, will not count as a failure. However, patients left with clinically concerning aneurysm residuals (in the opinion of the treating physician) after the treatment attempt will count as a failure of the initial treatment.
Outcome Time Frame
within 48 hours after attempted treatment
Outcome Measure
Failure of aneurysm occlusion using the intended treatment modality
Outcome Description
Mortality and morbidity from all causes will be recorded, along with cause of death, at one and five years.
Outcome Time Frame
one year and five years
Outcome Measure
Overall mortality and morbidity
Outcome Description
Determined using non-invasive angiography (CTA or MRA)as part of normal follow-up after aneurysm treatment. Although DSA, CTA and MRA are known to have different sensitivities in detecting aneurysm remnants,these modalities are equally well-suited to the discovery of a concerning, saccular aneurysm residual or remnant.
Outcome Time Frame
12 months (+/- 2 months)
Outcome Measure
Occurence of a "major" (saccular) aneurysm recurrence
Outcome Description
Will be recorded by the local treating physician upon discharge.
Outcome Time Frame
within a month or at discharge if earlier
Outcome Measure
Peri-treatment hospitalization lasting more than 20 days and/or discharge to a location other than home
Outcome Description
Repeat intracranial hemorrhage will be judged from cross-sectional imaging (CT scan), after worsening of headache, or following a new-onset neurological deficit or sudden death while awaiting treatment.
Outcome Time Frame
Within a few hours (while awaiting treatment)
Outcome Measure
Occurence of aneurysm re-rupture following randomization but before treatment initiation
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
David Altschul
Investigator Email
daltschu@montefiore.org
Investigator Phone
718-920-7498