Clinical Trial: International Subarachnoid Aneurysm Trial II

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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.

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 Summary:

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 impro
Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Current 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.


Original Secondary Outcome: Same as current

Information By: Centre hospitalier de l'Université de Montréal (CHUM)

Dates:
Date Received: August 15, 2012
Date Started: October 2012
Date Completion: June 2024
Last Updated: November 17, 2016
Last Verified: November 2016