International Subarachnoid Aneurysm Trial II (ISATII)

August 13, 2024 updated by: Centre hospitalier de l'Université de Montréal (CHUM)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

1724

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Foothills Medical Centre
      • Edmonton, Alberta, Canada
        • University of Alberta Hospital
    • Quebec
      • Montreal, Quebec, Canada, H2X 0C1
        • Centre Hospitalier de l'Université de Montréal - Hôpital Notre Dame
  • Spain
      • Barcelona, Spain
        • Vall d'Hebron Hospital
      • Valladolid, Spain
        • University of Valladolid
  • United States
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of an intracranial hemorrhage following treatment
Time Frame: one year
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.
one year
Failure of aneurysm occlusion using the intended treatment modality
Time Frame: within 48 hours after attempted treatment
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.
within 48 hours after attempted treatment
Overall mortality and morbidity
Time Frame: one year and five years
Mortality and morbidity from all causes will be recorded, along with cause of death, at one and five years.
one year and five years
Occurence of a "major" (saccular) aneurysm recurrence
Time Frame: 12 months (+/- 2 months)
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.
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
Will be recorded by the local treating physician upon discharge.
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)
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.
Within a few hours (while awaiting treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 12, 2012

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

August 15, 2012

First Submitted That Met QC Criteria

August 16, 2012

First Posted (Estimated)

August 20, 2012

Study Record Updates

Last Update Posted (Actual)

August 15, 2024

Last Update Submitted That Met QC Criteria

August 13, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CE 12.136

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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