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International Subarachnoid Aneurysm Trial II (ISAT II)

Primary Purpose

Intracranial Hemorrhage Ruptured Aneurysm

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
surgical management
Endovascular management
Sponsored by
Centre hospitalier de l'Université de Montréal (CHUM)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intracranial Hemorrhage Ruptured Aneurysm focused on measuring Aneurysm, Intracranial Aneurysm, Vascular Diseases, Cardiovascular Diseases, Intracranial Arterial Diseases, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Montefiore Medical CenterRecruiting
  • Foothills Medical Centre
  • University of Alberta HospitalRecruiting
  • Centre Hospitalier de l'Université de Montréal - Hôpital Notre DameRecruiting
  • Vall d'Hebron HospitalRecruiting
  • University of ValladolidRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Endovascular management

Surgical management

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Overall mortality and morbidity
Mortality and morbidity from all causes will be recorded, along with cause of death, at one 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.
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.
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.

Full Information

First Posted
August 15, 2012
Last Updated
July 4, 2023
Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
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1. Study Identification

Unique Protocol Identification Number
NCT01668563
Brief Title
International Subarachnoid Aneurysm Trial II
Acronym
ISAT II
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.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 12, 2012 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracranial Hemorrhage Ruptured Aneurysm
Keywords
Aneurysm, Intracranial Aneurysm, Vascular Diseases, Cardiovascular Diseases, Intracranial Arterial Diseases, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1724 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Endovascular management
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Surgical management
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
surgical management
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Endovascular management
Intervention Description
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.
Primary Outcome Measure Information:
Title
poor clinical outcome(mRS>2)
Description
Number of patients experiencing a poor clinical outcome at one year post-treatment, defined as a modified Rankin Scale (mRS) score of >2.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Occurrence of an intracranial hemorrhage following treatment
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.
Time Frame
one year
Title
Failure of aneurysm occlusion using the intended treatment modality
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.
Time Frame
within 48 hours after attempted treatment
Title
Overall mortality and morbidity
Description
Mortality and morbidity from all causes will be recorded, along with cause of death, at one and five years.
Time Frame
one year and five years
Title
Occurence of a "major" (saccular) aneurysm recurrence
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.
Time Frame
12 months (+/- 2 months)
Title
Peri-treatment hospitalization lasting more than 20 days and/or discharge to a location other than home
Description
Will be recorded by the local treating physician upon discharge.
Time Frame
within a month or at discharge if earlier
Title
Occurence of aneurysm re-rupture following randomization but before treatment initiation
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.
Time Frame
Within a few hours (while awaiting treatment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Roland Jabre, MD
Phone
514-890-8000
Ext
27235
Email
roland.jabre.med@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Guylaine Gevry
Phone
514-890-8000
Ext
27235
Email
guylaine.gevry.chum@ssss.gouv.qc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tim Darsaut, MD
Organizational Affiliation
University of Alberta
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Max Findlay, MD
Organizational Affiliation
University of Alberta
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David J Altschul, MD
Phone
718-920-7498
Email
DALTSCHU@montefiore.org
First Name & Middle Initial & Last Name & Degree
David J Altschul, MD
Facility Name
Foothills Medical Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
Individual Site Status
Completed
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tim Darsaut, MD, MSc
Email
tdarsaut@ualberta.ca
First Name & Middle Initial & Last Name & Degree
Tim Darsaut, MD, MSc
Facility Name
Centre Hospitalier de l'Université de Montréal - Hôpital Notre Dame
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 0C1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guylaine Gevry
Phone
1-514-890-8000
Ext
27235
Email
guylaine.gevry.chum@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name & Degree
Jean Raymond, MD
First Name & Middle Initial & Last Name & Degree
Daniel Roy, MD
First Name & Middle Initial & Last Name & Degree
Alain Weill, MD
First Name & Middle Initial & Last Name & Degree
Michel Bojanowski, MD
First Name & Middle Initial & Last Name & Degree
Chiraz Chaalala, MD
Facility Name
Vall d'Hebron Hospital
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jordi Vilalta, MD
Phone
93 489 38 91
Email
pelagatosiv@gmail.com
Facility Name
University of Valladolid
City
Valladolid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Herrero Rosario Sarabia, MD
First Name & Middle Initial & Last Name & Degree
Ignacio Arrese Reganon, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
12414200
Citation
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.
Results Reference
background
PubMed Identifier
16364540
Citation
Gnanalingham 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.
Results Reference
background
PubMed Identifier
22054213
Citation
McDougall 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.
Results Reference
background
PubMed Identifier
22481029
Citation
Raymond 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.
Results Reference
background
PubMed Identifier
23714335
Citation
Darsaut 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.
Results Reference
derived

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International Subarachnoid Aneurysm Trial II

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