International Subarachnoid Aneurysm Trial II (ISAT II)

This study is currently recruiting participants.
Verified March 2014 by Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor:
Information provided by (Responsible Party):
Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier:
NCT01668563
First received: August 15, 2012
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Intracranial Hemorrhage Ruptured Aneurysm
Procedure: surgical management
Procedure: Endovascular management

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Centre hospitalier de l'Université de Montréal (CHUM):

Primary Outcome Measures:
  • poor clinical outcome(mRS>2) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: within 48 hours after attempted treatment ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: one year and five years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 12 months (+/- 2 months) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: within a month or at discharge if earlier ] [ Designated as safety issue: Yes ]
    Will be recorded by the local treating physician upon discharge.

  • Occurence of aneurysm re-rupture following randomization but before treatment initiation [ Time Frame: Within a few hours (while awaiting treatment) ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 1724
Study Start Date: October 2012
Estimated Study Completion Date: June 2024
Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Endovascular management
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.
Procedure: Endovascular management
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.
Active Comparator: Surgical management
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.
Procedure: surgical management
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.

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 wideneck 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01668563

Contacts
Contact: Jean Raymond, MD 514-890-8000 ext 27235 jraymond.nri@gmail.com
Contact: Suzanne Nolet 514-890-8000 ext 26359 Suzanne.Nolet@crchum.qc.ca

Locations
Canada, Alberta
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Brenda D Poworoznik    780-863-5354    brenda.poworoznik@albertahealthservices.ca   
Principal Investigator: Tim Darsaut, MD         
Canada, Quebec
Centre hospitalier de l'Université de Montréal Recruiting
Montreal, Quebec, Canada, H2L 4M1
Contact: Suzanne Nolet    514-890-8000 ext 26359    Suzanne.Nolet@crchum.qc.ca   
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Investigators
Principal Investigator: Tim Darsaut, MD University of Alberta
Principal Investigator: Max Findlay, MD University of Alberta
Principal Investigator: Jean Raymond, MD Centre Hospitalier de l'Université de Montréal
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT01668563     History of Changes
Other Study ID Numbers: CE 12.136
Study First Received: August 15, 2012
Last Updated: March 18, 2014
Health Authority: Canada: Ethics Review Committee

Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):
Aneurysm
Intracranial Aneurysm
Vascular Diseases
Cardiovascular Diseases
Intracranial Arterial Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

Additional relevant MeSH terms:
Aneurysm
Intracranial Aneurysm
Hemorrhage
Intracranial Hemorrhages
Aneurysm, Ruptured
Rupture
Vascular Diseases
Cardiovascular Diseases
Intracranial Arterial Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pathologic Processes
Wounds and Injuries

ClinicalTrials.gov processed this record on April 17, 2014