Surveillance Versus Treatment of Unruptured Intracranial Aneurysms of Fortuitous Discovery : a Randomized Controlled Trial STAF Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Occurrence of a clinically significant event
研究概览
简要总结
The goal of this clinical trial is to determine whether a watchful waiting strategy with imaging surveillance is superior to immediate aneurysm treatment in adults with incidentally discovered unruptured intracranial aneurysms (UIAs).
The main questions it aims to answer are:
- Does watchful waiting reduce the risk of clinically significant neurological disability compared with immediate treatment?
- How do the two strategies compare in terms of aneurysm rupture, treatment-related complications, quality of life, anatomical outcomes, and healthcare costs?
Researchers will compare two management strategies:
- Immediate selective treatment of the aneurysm (endovascular or neurosurgical treatment according to standard practice).
- Watchful waiting with regular clinical and imaging follow-up and no initial aneurysm treatment.
Participants will:
- Be randomly assigned to either immediate treatment or watchful waiting.
- Undergo routine clinical assessments and annual brain imaging for at least 42 months.
- Complete quality-of-life questionnaires (EQ-5D-5L) at baseline and annually during follow-up.
- Participate in annual telephone follow-up assessments, including evaluation of functional outcome using the modified Rankin Scale (mRS).
- Undergo a blood or urine pregnancy test at enrollment if they are women of childbearing potential.
The study includes adults aged 35 years or older with incidentally discovered, non-infectious, intradural saccular UIAs measuring between 2.0 mm and 7.9 mm and no history of subarachnoid hemorrhage. The primary objective is to compare the impact of the two management strategies on neurological dependency during follow-up.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
This is an open-label trial; participants and treating physicians are not blinded to treatment allocation. However, outcome assessment includes blinded and independent evaluation components. The modified Rankin Scale (mRS) is assessed by an independent neurologist blinded to treatment allocation at baseline, at hospital discharge after aneurysm treatment, at the final study visit, and in case of suspected neurological deterioration identified during follow-up.
In addition, all primary outcome events are reviewed by an independent adjudication committee. The committee is not blinded to treatment allocation and evaluates whether each clinically significant event (defined as mRS ≥2 persisting for more than 90 days) is attributable to the natural history of the aneurysm or to its preventive treatment.
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •UIA (Unruptured Intracranial Aneurysms) located in an intradural position, with confirmed presence on CT (Computed Tomography) angiography or conventional cerebral angiography.
- •Largest diameter between 2 mm and 7.9 mm inclusive in height or width (excluding oblique measurements).
- •Patients with one or more UIAs, provided that at least one aneurysm (index aneurysm) fulfills all inclusion criteria and is selected for study evaluation.
- •Patients aged ≥ 35 years to 75 years.
- •Patients must have signed informed consent.
- •Patients must be affiliated with the French healthcare system.
排除标准
- •Aneurysms deemed inoperable by endovascular or surgical techniques, and patients with absolute contraindications to anaesthesia.
- •Patients with a disease reducing life expectancy to less than 3 years.
- •Patients with a mRS score of ≥
- •Patients with a history of prior treatment for a cerebral aneurysm (ruptured or unruptured).
- •History of unexplained SAH (Subarachnoid Haemorrhage).
- •UIA discovered in the context of a recent thunderclap or exertional headache.
- •Fusiform, mycotic, or intracavernous UIAs.
- •Infundibulum of the posterior communicating artery (PcomA) and choroidal artery.
- •Very distal saccular UIAs: A3/A4, M3/M4, P3/P
- •UIA associated with brain AVM (Arteriovenous Malformation).
- •Patients presenting with multiple UIAs in whom at least one aneurysm measures ≥ 8 mm, in order to avoid inclusion of patients at higher overall rupture risk not compatible with the study population.
- •Pregnancy or a desire for pregnancy during the study period.
- •Patients with autosomal dominant polycystic kidney disease (ADPKD), hereditary connective tissue disorders (HCTDs), or sickle cell disease (SCD).
- •Current participation in another interventional research study.
- •Patients likely to fail to attend follow-up visits or adhere to the protocol.
- •Allergy to iodinated contrast material.
- •Severe renal impairment (Glomerular Filtration Rate (GFR) < 30 mL/min/1.73m2).
研究组 & 干预措施
Watchful waiting strategy
Participants randomized to the watchful waiting strategy will receive no immediate preventive treatment of the unruptured intracranial aneurysm.
This strategy consists of initial non-interventional management with standard clinical follow-up and annual brain imaging according to standard care.
In the case of patients with multiple aneurysms, all aneurysms will be monitored under the same watchful waiting protocol.
Selective treatment is not performed at baseline, but may be considered during follow-up if clinically indicated.
干预措施: Clinical and imaging surveillance (Other)
Intervention strategy
Participants undergo immediate preventive treatment of the incidentally discovered unruptured intracranial aneurysm using standard endovascular or neurosurgical techniques.
Post-procedural follow-up is conducted according to standard care (clinical follow-up and annual brain imaging).
干预措施: Endovascular or neurosurgical aneurysm treatment (Procedure)
结局指标
主要结局
Occurrence of a clinically significant event
时间窗: From randomization until the occurrence of a mRS score ≥ 2, assessed up to 90 days after occurence by an independent neurologist, blinded to treatment allocation
The primary outcome is the occurrence of a clinically significant event during follow-up (minimum duration 3.5 years - maximum 6.5 years, mean duration of 5 years). A clinically significant event is defined as the occurrence of a functional disability with a modified Rankin Scale (mRS) score ≥ 2, persisting for more than 90 days, attributable to the natural history of the aneurysm or to its preventive treatment, as adjudicated by an independent committee.
次要结局
- Distribution of modified Rankin Scale(Through study completion, an average of 5 years)
- Occurrence of a transient modified Rankin Scale ≥ 3(Up to the occurrence of a mRS score ≥ 3, assessed by an investigator)
- SAH occurrence(Through study completion, an average of 5 years)
- Rupture rate(Through study completion, an average of 5 years)
- Iatrogenic complications(Through study completion, an average of 5 years)
- Rate of Unruptured Intracranial Aneurysms-related (UIA) Adverse Events(Through study completion, an average of 5 years)
- Classification of treated aneurysms(through study completion, an average of 5 years)
- Economic evaluation (cost-utility analysis)(From inclusion visit until 42 months visit)
- Economic evaluation (cost-effectiveness analysis)(From inclusion visit until 42 months visit)
- Non-aneurysm-related death(Through study completion, an average of 5 years)