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Aspirin Treatment for Small Unruptured InTracranial Aneurysms With Ischemic cereBrovascuLar diseasE

Phase 3
Not yet recruiting
Conditions
Cerebrovascular Disease
Intracranial Aneurysm
Interventions
Registration Number
NCT05907902
Lead Sponsor
Beijing Tiantan Hospital
Brief Summary

The management of small unruptured intracranial aneurysms (UIA) with ischemic cerebrovascular disease (ICVD) has been a very controversial topic in neurosurgery. Thus, we initiated a multicenter, prospective, randomized controlled trial (PROBE) design to elucidate in UIA patients with ICVD who do not qualify for preventive endovascular or neurosurgical intervention whether aspirin treatment decreases the risk of aneurysm growth and rupture.

Detailed Description

Unruptured IAs are prevalent cerebrovascular disorders affecting approximately 3%-5% of the general population. The mortality rate associated with the rupture of UIAs stands at around 30%-40%, with over one-third of survivors experiencing significant neurological deficits. Currently, there are no established guidelines for the management of UIAs with ICVD. Our AIUIA trial is the inaugural randomized study investigating the potential of an anti-inflammatory strategy in mitigating aneurysm growth or rupture in patients with UIAs and ICVD who do not undergo preventive occlusion. It has the potential to provide level-A evidence that supports the aforementioned patient management approach.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
824
Inclusion Criteria
  • patients aged more than 18 and less than 80 years
  • patients with UIAs < 5 and ≥2 mm in the greatest diameter confirmed by MR angiography (MRA), computed tomography angiography (CTA) , or digital subtraction angiography (DSA)
  • patients with either symptomatic ICVD (ischemic stroke or transient ischemic attack) or asymptomatic ICVD (clinically silent lacunar infarction identified on brain CT/MR imaging)
  • last aneurysm imaging with either CTA or MRA or DSA within the last 3 months
  • ability of the subject to understand character and individual consequences of clinical trial
  • patients who provided written informed consent
  • patients who consented to follow-up imaging with the same MR angiography or CT angiography modality
Exclusion Criteria
  • multiple aneurysms
  • a history of intracranial aneurysm rupture-related hemorrhage
  • a family history of intracranial aneurysm
  • a history of vascular malformation (brain arteriovenous malformation, moyamoya disease, arteriovenous fistula, etc.), brain tumor, hydrocephalus, or hypertensive cerebral hemorrhage etc.
  • MR contraindications (metallic implant, contrast medium allergy, claustrophobia, etc).
  • a precondition modified Rankin Scale (mRS) score > 2
  • fusiform or daughter sac UIAs
  • an allergy to aspirin
  • other contraindications for aspirin not yet mentioned, in the dosage of 100 mg/day (e.g. bleeding disorders, gastric or intestinal ulcers, acute liver failure or kidney failure, severe heart failure, treatment with methotrexate in a dosage 15 mg/week or above)
  • pregnancy and lactation
  • participation in another clinical trial or observation period of competing trials
  • residence in a rural area that prevented regular follow-up
  • poor compliance

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AspirinAspirin Enteric-coated Tabletslow-dose aspirin, 100 mg once daily, one 100mg tablet
Primary Outcome Measures
NameTimeMethod
number of participants with aneurysm rupture or growth24 months

primary composite outcome involving aneurysm growth ((1) ≥1.0mm in at least 1 direction by identical imaging modalities, (2) ≥0.5 mm in 2 directions by identical imaging modalities, and (3) an indisputable change in aneurysm shape) or rupture on repeated magnetic resonance- or CT-angiography within 24 months after randomization.

Secondary Outcome Measures
NameTimeMethod
number of participants with aneurysm rupture24 months

Individual components of the primary composite outcome, aneurysm rupture within 24 months after randomization.

degree of C-reaction protein level change24 months

change of inflammatory biomarkers, serum C-reaction protein level

degree of cytokines level change24 months

change of inflammatory biomarkers, cytokines including TNF-α, IL-6, IL-8, IL-10, IL-1β, IL-2R etc.

any hemorrhagic stroke24 months

the incidence of any hemorrhagic stroke, defined as the acute extravasation of blood into the brain parenchyma or subarachnoid space with associated neurological symptoms and a bleeding area far from the aneurysm location

any systematic bleeding24 months

the incidence of systematic bleeding

all cause mortality24 months

rate of overall mortality

number of participants with de novo aneurysm on repeated angiography24 months

development of de novo aneurysm on serial imaging

number of participants with aneurysm growth on repeated angiography24 months

Individual components of the primary composite outcome, aneurysm growth ((1) ≥1.0mm in at least 1 direction by identical imaging modalities, (2) ≥0.5 mm in 2 directions by identical imaging modalities, and (3) an indisputable change in aneurysm shape) on repeated magnetic resonance- or CT-angiography or DSA within 24 months after randomization.

recurrent or new ischemic events24 months

the incidence of recurrent or new ischemic events (symptoms suggestive of ischemic stroke or transient ischemic attack (TIA) and confirmed by neurologists in the town/village clinic of their choice)

adverse events (AEs)/serious adverse events (SAEs)24 months

all adverse and serious adverse events pertaining to the aspirin

Trial Locations

Locations (2)

Beijing Tsinghua Changgung Hospital

🇨🇳

Beijing, Beijing, China

Beijing Tongren Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

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