Aspirin Treatment for Small Unruptured InTracranial Aneurysms With Ischemic cereBrovascuLar diseasE

Intracranial Aneurysm Clinical Trial

— AT-SUITABLE  

Official title:

Aspirin Treatment for Small Unruptured InTracranial Aneurysms With Ischemic cereBrovascuLar diseasE (AT-SUITABLE): a Phase 3, Multicenter, Prospective, Randomized, Open-label, Blinded-endpoint Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05907902
• Other study ID #: 2022-I2M-C&T-B-114
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 1, 2023
• Est. completion date: July 1, 2025

Study information

• Verified date: June 2023
• Source: Beijing Tiantan Hospital
• Contact: Yong Cao, MD
• Phone: +86 (010)59976510
• Email: caoyong6[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 824
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Aneurysm
• Cerebrovascular Disease
• Cerebrovascular Disorders
• Intracranial Aneurysm

Intervention

Drug:
• Aspirin Enteric-coated Tablets
low-dose aspirin 100 mg once daily (one 100mg tablet).

Locations

Country	Name	City	State
China	Beijing Tongren Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Tsinghua Changgung Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

Weng JC, Wang J, Du X, Li H, Jiao YM, Fu WL, Huo R, Yan ZH, Xu HY, Wang S, Cao Y, Zhao JZ; Small Unruptured Aneurysms Study Group. Safety of Aspirin Use in Patients With Stroke and Small Unruptured Aneurysms. Neurology. 2021 Jan 5;96(1):e19-e29. doi: 10.1 — View Citation

Weng JC, Wang J, Li H, Jiao YM, Fu WL, Huo R, Yan ZH, Xu HY, Zhan J, Wang S, Du X, Cao Y, Zhao JZ; Small Unruptured Aneurysms Study Group. Aspirin and Growth of Small Unruptured Intracranial Aneurysm: Results of a Prospective Cohort Study. Stroke. 2020 Oc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of participants with aneurysm rupture or growth	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.	24 months
Secondary	number of participants with aneurysm rupture	Individual components of the primary composite outcome, aneurysm rupture within 24 months after randomization.	24 months
Secondary	number of participants with aneurysm growth on repeated angiography	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.	24 months
Secondary	degree of C-reaction protein level change	change of inflammatory biomarkers, serum C-reaction protein level	24 months
Secondary	degree of cytokines level change	change of inflammatory biomarkers, cytokines including TNF-a, IL-6, IL-8, IL-10, IL-1ß, IL-2R etc.	24 months
Secondary	recurrent or new ischemic events	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)	24 months
Secondary	any hemorrhagic stroke	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	24 months
Secondary	any systematic bleeding	the incidence of systematic bleeding	24 months
Secondary	all cause mortality	rate of overall mortality	24 months
Secondary	number of participants with de novo aneurysm on repeated angiography	development of de novo aneurysm on serial imaging	24 months
Secondary	adverse events (AEs)/serious adverse events (SAEs)	all adverse and serious adverse events pertaining to the aspirin	24 months