Why IUAT

The scientific and clinical rationale for IUAT, including the evidence gap, contemporary surgical risk data, the mRS ceiling effect and unwarranted practice variation.

A common condition with an unresolved treatment decision

Unruptured intracranial aneurysms affect an estimated 2–5% of adults. Most will never rupture, but rupture carries high case fatality and substantial morbidity among survivors. Treatment itself carries procedural risk, particularly in neurologically intact elective patients.

The central clinical problem is not rare. It is common, consequential and unresolved.

The evidence gap

TEAM

TEAM attempted to randomise patients to endovascular treatment or conservative management. It stopped after enrolling only 80 of a planned 2,002 patients. The lesson is important for IUAT: treatment-versus-observation is extremely difficult to recruit once a patient knows they have an aneurysm.

CURES

CURES showed that a clipping-versus-endovascular trial is deliverable, but it was a pilot study. It enrolled 291 patients, used a 1-year imaging-dominated endpoint, and did not test the contemporary endovascular portfolio now used in routine practice.

PRAEMIUM

PRAEMIUM provides contemporary surgical risk benchmarks from expert centres. This matters because a rigorous new trial needs credible, contemporary estimates of procedural risk.

Cochrane and contemporary reviews

Systematic reviews continue to confirm the absence of definitive randomised evidence in this area. Further meta-analysis of non-randomised data will not resolve the question.

Why now

• Contemporary EVT now includes intrasaccular devices and flow diversion, not just conventional coiling.
• The CURES pilot has already shown that treatment-versus-treatment randomisation is possible.
• PRAEMIUM provides surgical risk benchmarks that were previously missing.
• There is substantial unwarranted variation in practice across countries and centres.
• Patient-centred outcomes now allow a better trial endpoint than mRS alone.

The practice variation problem

There are marked regional differences in clipping and coiling rates, ranging from near-complete endovascular practice in some settings to high clipping rates in others. This degree of variation is difficult to justify..

IUAT is designed to replace centre culture with randomised evidence.

The endpoint problem

Traditional mRS outcomes have a ceiling effect in elective unruptured aneurysm patients. Many patients remain mRS 0–2 regardless of treatment, while differences in fatigue, cognition, anxiety, participation and return to work may still be clinically meaningful.

IUAT addresses this by using a hierarchical outcome structure:

1. Safety first: death or major disabling stroke.
2. Patient-centred function: COSMOS at 12 months.
3. Recovery trajectory: length of stay, days at home and time to return to work or role.

This structure makes the trial clinically safer and more interpretable: recovery benefit cannot outweigh major harm.