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NCT Number: NCT01668563

International Subarachnoid Aneurysm Trial II

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Foothills Medical Centre, Calgary, Alberta, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Surgical management

Procedure

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 management

Procedure

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 outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

Sponsors and collaborators

Lead sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Other

Registry information

Official study 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.

Acronym: ISATII

Important dates

Study start
2012
Primary completion
2024
Study completion
2024
First posted
Aug 20, 2012
Registry last updated
Aug 15, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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