Surveillance Versus Treatment of Unruptured Intracranial Aneurysms of Fortuitous Discovery

Over the past two decades, the development of non-invasive cerebral vascular imaging and the ageing of the Western population have contributed to the diagnosis of an increasing number of fortuitous unruptured intracranial aneurysms (UIAs), of which approximately 80% measure less than 8 mm in diameter. Neuroradiology and neurosurgery teams have long considered that these UIAs should be treated to protect patients from the risk of subarachnoid haemorrhage (SAH).

The medical community is currently deeply divided regarding the management of these incidentally discovered lesions, with some teams advocating systematic treatment, while others favor radiological surveillance. This divergence reflects a significant degree of uncertainty, thereby justifying the undertaking of a prospective randomized study comparing treatment strategies with surveillance.

The STAF study is designed to evaluate whether a conservative management strategy based on watchful waiting and imaging surveillance is superior to immediate aneurysm treatment with regard to long-term neurological outcomes. The study hypothesis is that patients undergoing immediate aneurysm treatment will experience a higher rate of clinically significant neurological disability than patients managed conservatively. Clinically significant disability is defined as a modified Rankin Scale (mRS) score ≥2 persisting for more than 90 days.

STAF is a prospective, national, multicenter, randomized, open-label, parallel-group trial with adjudication of events ("Prospective Randomized Open-label Blinded Endpoint" PROBE study design). Approximately 7 to 10 neuroradiology and neurosurgery centers across France will participate and recrute in the study.

This study enrolls adult participants with incidentally discovered UIAs. Following incidental aneurysm detection during routine clinical care, patients will be referred to an interventional neuroradiologist or neurosurgeon. During the screening visit, aneurysm characteristics and eligibility criteria will be assessed, and study information will be provided.

Eligible patients will return for an inclusion visit within three months, during which eligibility will be confirmed, written informed consent obtained, and randomization performed. Randomization will be conducted through an Interactive Web Response System (IWRS) using a 1:1 allocation ratio between the two study groups. Randomization will be stratified by participating center, age category (35-55 years versus 56-75 years), and aneurysm size (<5 mm versus ≥5 mm).

Participants randomized to the intervention strategy will undergo selective aneurysm treatment according to standard clinical practice, including either endovascular or neurosurgical treatment as determined by the treating physicians. Participants randomized to the watchful waiting strategy will receive no initial selective aneurysm treatment.

All participants will be followed according to routine clinical practice, including annual consultation visits and cerebral imaging performed in accordance with current American Heart Association/American Stroke Association recommendations. To ensure regular assessment of functional status from screening to the end-of-study visit, participants will also be contacted annually by a brief telephone follow-up, scheduled approximately 6 months after their previous on-site visit.

All randomized patients will be followed for a minimum of 3,5 years (i.e. 42 months for the last included patients) to a maximum of 6,5 years (i.e. 78 months for the first included patients) with a mean follow-up of 5 years.

Because of the prolonged follow-up period and the possibility of clinical events unrelated to aneurysm disease or treatment, all major study outcomes will be independently adjudicated to determine whether they are related or unrelated to aneurysm progression or treatment.

The primary objective is to compare the effect of immediate aneurysm treatment versus watchful waiting on neurological dependency during follow-up. Secondary objectives include comparison of subarachnoid hemorrhage rates, evaluation of the safety, assessment of treated aneurysm anatomical outcomes through imaging review and economic evaluation of the two management strategies.