Aspirin Treatment for Small Unruptured InTracranial Aneurysms With Ischemic cereBrovascuLar diseasE (AT-SUITABLE)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Intracranial Aneurysm; Cerebrovascular Disease
• Intervention / Treatment: Drug: Aspirin Enteric-coated Tablets

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.

• Study Type: Interventional
• Enrollment (Estimated): 824
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yong Cao, MD; Phone Number: +86 (010)59976510; Email: caoyong6@hotmail.com
• Study Contact Backup: Name: Fa Lin, MD; Phone Number: +86 13681107240; Email: 13681107240@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 102218
      • Beijing Tsinghua Changgung Hospital
      • Contact: Yi Guo, MD; Email: ghuoyi@gmail.com
      • Principal Investigator: Yi Guo, MD
    • Beijing, Beijing, China, 100730
      • Beijing tongren Hospital, Capital Medical University
      • Contact: Jun Kang, MD; Email: junkang2015@163.com
      • Principal Investigator: Jun Kang, Kang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin; low-dose aspirin, 100 mg once daily, one 100mg tablet	Drug: Aspirin Enteric-coated Tablets; low-dose aspirin 100 mg once daily (one 100mg tablet).; Other Names: Bayer
No Intervention: standard protocol; standard of care, UIA management according to guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of participants with aneurysm rupture	Individual components of the primary composite outcome, aneurysm rupture within 24 months after randomization.	24 months
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
degree of C-reaction protein level change	change of inflammatory biomarkers, serum C-reaction protein level	24 months
degree of cytokines level change	change of inflammatory biomarkers, cytokines including TNF-α, IL-6, IL-8, IL-10, IL-1β, IL-2R etc.	24 months
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
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
any systematic bleeding	the incidence of systematic bleeding	24 months
all cause mortality	rate of overall mortality	24 months
number of participants with de novo aneurysm on repeated angiography	development of de novo aneurysm on serial imaging	24 months
adverse events (AEs)/serious adverse events (SAEs)	all adverse and serious adverse events pertaining to the aspirin	24 months

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Yong Cao, MD, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University

Publications and helpful links

General Publications

• 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: 10.1212/WNL.0000000000010997. Epub 2020 Oct 14.
• 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 Oct;51(10):3045-3054. doi: 10.1161/STROKEAHA.120.029967. Epub 2020 Sep 3.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: May 22, 2023
• First Submitted That Met QC Criteria: June 14, 2023
• First Posted (Estimated): June 16, 2023

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; aspirin; Intracranial Aneurysm; ischemic cerebrovascular disease; Cerebrovascular Diseases
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Aneurysm; Cerebrovascular Disorders; Intracranial Aneurysm; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: 2022-I2M-C&T-B-114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No