Intracranial Hemorrhage Ruptured AneurysmISATIINCT01668563
International Subarachnoid Aneurysm Trial II
A study testing surgical management and Endovascular management in people with Intracranial Hemorrhage Ruptured Aneurysm, run by Centre hospitalier de l'Université de Montréal (CHUM) at 6 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracranial Hemorrhage Ruptured Aneurysm
- What is being tested?
- surgical management and Endovascular management
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,724 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 12 Nov 2012to Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Patients with absolute contraindications administration of contrast material (any type)
- Patients with AVM-associated aneurysms
- Aneurysm located at basilar apex
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Canada3 sites
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
University of Alberta Hospital
Edmonton, Alberta
Centre Hospitalier de l'Université de Montréal - Hôpital Notre Dame
Montreal, Quebec, H2X 0C1
Spain2 sites
Vall d'Hebron Hospital
Barcelona
University of Valladolid
Valladolid
United States1 site
Montefiore Medical Center
The Bronx, New York, 10467
About this study
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.
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.
Read the 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.
- Being tested
- surgical management, Endovascular management
- Keywords
- Aneurysm, Intracranial Aneurysm, Vascular Diseases, Cardiovascular Diseases, Intracranial Arterial Diseases, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases
- Medical subject headings
- Aneurysm, Intracranial Aneurysm, Vascular Diseases, Cardiovascular Diseases, Intracranial Arterial Diseases, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
surgical managementProcedure or surgery
Surgical clipping will be performed as soon as possible following randomization, according to standards of practice, and under general anesthesia. Aneurysms thought by the treating physicians to require deliberate permanent proximal vessel occlusion, construction of a surgical bypass, or other flow-redirecting treatments that do not directly clip the aneurysm will not be excluded; these non-ISAT aneurysms are expected to be more difficult lesions to manage surgically as well as endovascularly.
Endovascular managementProcedure or surgery
Endovascular treatment will also be performed as soon as possible following randomization,according to standards of practice, and under general anesthesia. Details regarding type of coils, use of adjunctive techniques such as balloon-remodeling, stents or flow-diverters, as well as post-treatment medical management issues, will be left up to the physician performing the endovascular treatment.
| Study group | Role | What they receive |
|---|---|---|
| Endovascular management | Active comparator | Endovascular treatment will be performed as soon as possible following randomization, according to standards of practice, and under general anesthesia. Details regarding type of coils, use of adjunctive techniques such as balloon-remodeling, stents or flow-diverters, as well as post-treatment medical management issues, will be left up to the physician performing the endovascular treatment. Receives: Procedure: Endovascular management |
| Surgical management | Active comparator | Surgical clipping will be performed as soon as possible following randomization, according to standards of practice, and under general anesthesia. Aneurysms thought by the treating physicians to require deliberate permanent proximal vessel occlusion, construction of a surgical bypass, or other flow-redirecting treatments that do not directly clip the aneurysm will not be excluded; these non-ISAT aneurysms are expected to be more difficult lesions to manage surgically as well as endovascularly. Receives: Procedure: surgical management |
What is being measured
The primary outcome is the main question the study is designed to answer.
poor clinical outcome(mRS>2)
Number of patients experiencing a poor clinical outcome at one year post-treatment, defined as a modified Rankin Scale (mRS) score of >2.
Measured: 12 months
Secondary outcomes (6)
Occurrence of an intracranial hemorrhage following treatment
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.
Measured: one year
Failure of aneurysm occlusion using the intended treatment modality
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.
Measured: within 48 hours after attempted treatment
Overall mortality and morbidity
Mortality and morbidity from all causes will be recorded, along with cause of death, at one and five years.
Measured: one year and five years
Occurence of a "major" (saccular) aneurysm recurrence
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.
Measured: 12 months (+/- 2 months)
Peri-treatment hospitalization lasting more than 20 days and/or discharge to a location other than home
Will be recorded by the local treating physician upon discharge.
Measured: within a month or at discharge if earlier
Occurence of aneurysm re-rupture following randomization but before treatment initiation
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.
Measured: Within a few hours (while awaiting treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2012 (estimated)
- Study start12 Nov 2012
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Intracranial Hemorrhage Ruptured AneurysmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,724 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tim Darsaut, MD, Principal investigator, University of AlbertaMax Findlay, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01668563
- Sponsor's protocol ID
- CE 12.136
- Acronym
- ISATII
- Status last verified
- Aug 2024
- First submitted
- 15 Aug 2012
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Molyneux A, Kerr R, Stratton I, Sandercock P, Clarke M, Shrimpton J, Holman R; International Subarachnoid Aneurysm Trial (ISAT) Collaborative Group. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet. 2002 Oct 26;360(9342):1267-74. doi: 10.1016/s0140-6736(02)11314-6.
PubMed 12414200Gnanalingham KK, Apostolopoulos V, Barazi S, O'Neill K. The impact of the international subarachnoid aneurysm trial (ISAT) on the management of aneurysmal subarachnoid haemorrhage in a neurosurgical unit in the UK. Clin Neurol Neurosurg. 2006 Feb;108(2):117-23. doi: 10.1016/j.clineuro.2005.11.001. Epub 2005 Dec 20.
PubMed 16364540McDougall CG, Spetzler RF, Zabramski JM, Partovi S, Hills NK, Nakaji P, Albuquerque FC. The Barrow Ruptured Aneurysm Trial. J Neurosurg. 2012 Jan;116(1):135-44. doi: 10.3171/2011.8.JNS101767. Epub 2011 Nov 4.
PubMed 22054213Raymond J, Kotowski M, Darsaut TE, Molyneux AJ, Kerr RS. Ruptured aneurysms and the International Subarachnoid Aneurysm Trial (ISAT): What is known and what remains to be questioned. Neurochirurgie. 2012 Apr-Jun;58(2-3):103-14. doi: 10.1016/j.neuchi.2012.02.020. Epub 2012 Apr 4. English, French.
PubMed 22481029Darsaut TE, Jack AS, Kerr RS, Raymond J. International Subarachnoid Aneurysm Trial - ISAT part II: study protocol for a randomized controlled trial. Trials. 2013 May 29;14:156. doi: 10.1186/1745-6215-14-156.
PubMed 23714335
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01668563
- Acronym / sponsor ID
- ISATII / CE 12.136
- Keywords
- Aneurysm, Intracranial Aneurysm, Vascular Diseases, Cardiovascular Diseases, Intracranial Arterial Diseases, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,724 participants (estimated)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Study start
- 12 Nov 2012 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 20 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Endovascular management | Active comparator | Procedure: Endovascular managementEndovascular treatment will be performed as soon as possible following randomization, according to standards of practice, and under general anesthesia. Details regarding type of coils, use of adjunctive techniques such as balloon-remodeling, stents or flow-diverters, as well as post-treatment medical management issues, will be left up to the physician performing the endovascular treatment. |
| Surgical management | Active comparator | Procedure: surgical managementSurgical clipping will be performed as soon as possible following randomization, according to standards of practice, and under general anesthesia. Aneurysms thought by the treating physicians to require deliberate permanent proximal vessel occlusion, construction of a surgical bypass, or other flow-redirecting treatments that do not directly clip the aneurysm will not be excluded; these non-ISAT aneurysms are expected to be more difficult lesions to manage surgically as well as endovascularly. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- Patients with absolute contraindications administration of contrast material (any type)
- Patients with AVM-associated aneurysms
- Aneurysm located at basilar apex
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| surgical managementSurgical clipping will be performed as soon as possible following randomization, according to standards of practice, and under general anesthesia. Aneurysms thought by the treating physicians to require deliberate permanent proximal vessel occlusion, construction of a surgical bypass, or other flow-redirecting treatments that do not directly clip the aneurysm will not be excluded; these non-ISAT aneurysms are expected to be more difficult lesions to manage surgically as well as endovascularly. | Procedure or surgery | Surgical management |
| Endovascular managementEndovascular treatment will also be performed as soon as possible following randomization,according to standards of practice, and under general anesthesia. Details regarding type of coils, use of adjunctive techniques such as balloon-remodeling, stents or flow-diverters, as well as post-treatment medical management issues, will be left up to the physician performing the endovascular treatment. | Procedure or surgery | Endovascular management |
Primary outcome
poor clinical outcome(mRS>2)
Time frame: 12 months
Number of patients experiencing a poor clinical outcome at one year post-treatment, defined as a modified Rankin Scale (mRS) score of >2.
6 secondary outcomes
Occurrence of an intracranial hemorrhage following treatment
Time frame: one year
Failure of aneurysm occlusion using the intended treatment modality
Time frame: within 48 hours after attempted treatment
Overall mortality and morbidity
Time frame: one year and five years
Occurence of a "major" (saccular) aneurysm recurrence
Time frame: 12 months (+/- 2 months)
Peri-treatment hospitalization lasting more than 20 days and/or discharge to a location other than home
Time frame: within a month or at discharge if earlier
Occurence of aneurysm re-rupture following randomization but before treatment initiation
Time frame: Within a few hours (while awaiting treatment)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2024.
- Background: PubMed 12414200Molyneux A, Kerr R, Stratton I, Sandercock P, Clarke M, Shrimpton J, Holman R; International Subarachnoid Aneurysm Trial (ISAT) Collaborative Group. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet. 2002 Oct 26;360(9342):1267-74. doi: 10.1016/s0140-6736(02)11314-6.
- Background: PubMed 16364540Gnanalingham KK, Apostolopoulos V, Barazi S, O'Neill K. The impact of the international subarachnoid aneurysm trial (ISAT) on the management of aneurysmal subarachnoid haemorrhage in a neurosurgical unit in the UK. Clin Neurol Neurosurg. 2006 Feb;108(2):117-23. doi: 10.1016/j.clineuro.2005.11.001. Epub 2005 Dec 20.
- Background: PubMed 22054213McDougall CG, Spetzler RF, Zabramski JM, Partovi S, Hills NK, Nakaji P, Albuquerque FC. The Barrow Ruptured Aneurysm Trial. J Neurosurg. 2012 Jan;116(1):135-44. doi: 10.3171/2011.8.JNS101767. Epub 2011 Nov 4.
- Background: PubMed 22481029Raymond J, Kotowski M, Darsaut TE, Molyneux AJ, Kerr RS. Ruptured aneurysms and the International Subarachnoid Aneurysm Trial (ISAT): What is known and what remains to be questioned. Neurochirurgie. 2012 Apr-Jun;58(2-3):103-14. doi: 10.1016/j.neuchi.2012.02.020. Epub 2012 Apr 4. English, French.
- Derived from this study: PubMed 23714335Darsaut TE, Jack AS, Kerr RS, Raymond J. International Subarachnoid Aneurysm Trial - ISAT part II: study protocol for a randomized controlled trial. Trials. 2013 May 29;14:156. doi: 10.1186/1745-6215-14-156.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim Darsaut, MD principal investigator
University of Alberta
Max Findlay, MD principal investigator
University of Alberta
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing surgical management and Endovascular management in people with Intracranial Hemorrhage Ruptured Aneurysm, run by Centre hospitalier de l'Université de Montréal (CHUM) at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada, Spain, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
poor clinical outcome(mRS>2) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01668563, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2024.