Efficacy and Safety of Methylprednisolone After Flow-Diverter Stent Implantation in Unruptured Intracranial Aneurysms

Overview

Study Title: Testing Methylprednisolone to Prevent Strokes After a Stent Procedure for Brain Aneurysms What is the purpose of this study? This study aims to find out if a short course of a steroid medicine called methylprednisolone can help prevent strokes and other brain-related complications in patients who have a "flow diverter" stent placed to treat an unruptured brain aneurysm. The main goal is to see if this treatment reduces the combined number of new strokes (both clot-related and bleeding-related) or brain injury-related deaths within the first 30 days after the procedure. Who can participate? Adults aged 18 or older with an unruptured brain aneurysm (size 3-25mm) who are scheduled to receive a flow-diverting stent and can provide informed consent may be eligible. Key reasons someone might not be able to join include: having multiple aneurysms needing quick treatment, being pregnant or breastfeeding, having a history of recent stroke, having active infections or stomach ulcers, having severe kidney disease, having very high/uncontrolled blood pressure or blood sugar, or already being on long-term steroid therapy. What will happen in the study? This is a multicenter, randomized, double-blind study. This means: Participants will be randomly assigned (like flipping a coin) to one of two groups. One group will receive methylprednisolone. The other group will receive a placebo (an inactive substance that looks identical). Neither the participants nor their doctors will know which treatment is being given. All participants will receive the standard care for the stent procedure and aftercare. How long will the study last? The treatment period is short (around the time of the procedure). Participants will be closely monitored in the hospital and will have a follow-up visit around 30 days after the procedure to check their health status. What will be measured? The researchers will mainly track whether participants have any stroke or brain injury-related death in the first 30 days. They will also check for other complications like bleeding, infections, and changes in daily function and quality of life. Safety will be monitored throughout. How many people will take part? The study plans to enroll approximately 864 participants across multiple hospitals. Study Dates: The study is expected to start enrolling patients in January 2026 and finish in August 2027. Who is organizing the study? This study is sponsored and led by Zhujiang Hospital, Southern Medical University.

Title: A Study on the Efficacy and Safety of Methylprednisolone in Preventing Cerebrovascular Adverse Events after Flow-Diverting Device Implantation in Patients with Unruptured Intracranial Aneurysms-A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Sponsor: Zhujiang Hospital, Southern Medical University Leading Institution: Zhujiang Hospital, Southern Medical University Research Objectives: Primary Objective: To evaluate the efficacy of methylprednisolone treatment on the composite outcome of any new cerebrovascular adverse event and neurologic death within 30 days after flow-diverting device implantation in patients with unruptured intracranial aneurysms (IAs). Secondary Objectives: 1. Incidence of any cerebrovascular adverse event (ischemic or hemorrhagic brain events) within 72 hours, 5 days, and 30 days post-operation. 2. Incidence of any ischemic brain event (ischemic stroke, in-stent thrombosis, urgent revascularization) within 72 hours, 5 days, and 30 days post-operation. 3. Incidence of any hemorrhagic brain event (intraparenchymal hemorrhage, subarachnoid hemorrhage, or subdural hematoma) within 72 hours, 5 days, and 30 days post-operation. 4. All-cause mortality within 30 days post-operation. 5. Proportion of patients with a modified Rankin Scale (mRS) score of 0-2 at 30 days post-operation. 6. Proportion of patients with an mRS score of 3-5 at 30 days post-operation. 7. Incidence of transient ischemic attack (TIA) within 72 hours post-operation. 8. EQ-5D score at 30 days post-operation. 9. Safety endpoint: Incidence of no new moderate or severe adverse events within 72 hours, 5 days, and 30 days post-operation. 10. Secondary safety endpoints: * Incidence of any intracranial hemorrhage within 72 hours post-medication. * Incidence of systemic bleeding complications (including gastrointestinal bleeding, systemic subcutaneous hemorrhage). * Incidence of non-hemorrhagic serious adverse events. * Incidence of gastrointestinal bleeding within 7 days post-operation. * Incidence of pulmonary infection during hospitalization. Research Hypothesis: Methylprednisolone treatment can effectively reduce the incidence of cerebrovascular adverse events and neurologic death within 30 days after flow-diverting device implantation in patients with unruptured intracranial aneurysms. Study Design: Multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. Sample Size: The study is designed as randomized, double-blind, parallel, placebo-controlled. The primary outcome is the composite cerebrovascular event within 30 days post-implantation, defined as any new target vessel-related event: (1) ischemic stroke, (2) hemorrhagic stroke, (3) neurologic death. Based on prior observational studies, the estimated primary outcome rate is 4.7% in the methylprednisolone group and 12.4% in the control group. With a two-sided significance level α=0.05 and power 1-β=0.80, the calculated sample size is approximately 203 per group. Accounting for a 5% dropout rate, 214 participants per group (428 total) are needed. Adopting a more conservative estimate (methylprednisolone group: 6.0%, placebo group: 11.5%), the calculated sample size is approximately 410 per group. With a 5% dropout rate, 432 participants per group (864 total) are needed. Study Population: Diagnostic Criteria: Patients with unruptured intracranial aneurysms confirmed by CTA, MRA, or DSA. Inclusion Criteria: 1. Age ≥ 18 years. 2. IA diagnosed by CTA, MRA, or DSA. 3. IA size between 3-25 mm. 4. Patient and/or legal representative understands the study purpose, volunteers to participate, and provides written informed consent. 5. Patients scheduled for flow-diverting device treatment. 6. Willing to undergo follow-up evaluations as per the study protocol. Exclusion Criteria: 1. Patients with two or more multiple aneurysms requiring treatment within one month. 2. Women who are planning pregnancy, pregnant, or breastfeeding. 3. Pre-morbid mRS score ≥ 2. 4. Patients with systemic infectious diseases (latent/active), ulcerative colitis, diverticulitis, liver cirrhosis, myasthenia gravis, ocular herpes simplex; contraindications to corticosteroids such as active peptic ulcer, severe fungal infection. 5. Ruptured, recurrent, infectious, or dissecting aneurysms; patients with arteriovenous malformation, dural arteriovenous fistula, spinal dural arteriovenous fistula, moyamoya disease, etc. 6. Symptomatic cerebral vascular stenosis ≥ 70%. 7. History of stroke (intracerebral hemorrhage, cerebral infarction) within the past 30 days. 8. Planned for other surgical/interventional procedures within 30 days. 9. Severe comorbidities unsuitable for anesthesia or surgery (e.g., major cardiac, pulmonary, hepatic, splenic, renal diseases, atrial fibrillation, brain tumor, severe active infection, DIC, severe psychiatric history). 10. Inability to receive antiplatelet or anticoagulant therapy. 11. Allergy to methylprednisolone sodium succinate. 12. Long-term preoperative hormone therapy (≥1 week) for other conditions. 13. Concomitant use of hepatic enzyme-inducing drugs (e.g., barbiturates, rifampin, carbamazepine, phenytoin) or inhibitors (e.g., erythromycin, ketoconazole). 14. Chronic hemodialysis or severe renal insufficiency (GFR \<30 ml/min or creatinine \>220 μmol/L). 15. Uncontrolled hypertension (SBP \>180 mmHg or DBP \>110 mmHg despite medication). 16. Blood glucose \<2.8 mmol/L or \>22.2 mmol/L. 17. Vaccination within the past month or planned vaccination. 18. Unwilling or unable to comply with follow-up requirements. 19. Life expectancy \<6 months due to any end-stage disease. 20. Participation in another clinical trial. Main Interventions: Experimental Group: Methylprednisolone treatment. Control Group: Placebo treatment. Follow-up: Within 24 hours post-surgery, within 72 hours post-surgery, at postoperative day 5/early discharge, and at 30±7 days. Evaluation Indicators: Primary Outcome: Incidence of the composite outcome of any new cerebrovascular adverse event and neurologic death within 30 days post-implantation. Secondary Outcomes: Incidence rates as specified in objectives (2) through (17) above at the defined time points. Statistical Methods: For the primary outcome, a Log-binomial regression model will be the primary method to calculate the Risk Ratio (RR) and 95% CI. A multivariate model adjusting for baseline variables (gender, age, aneurysm location, blood pressure grade) will be used. If convergence fails, robust Poisson regression or logistic regression will be employed as alternatives. A two-sided p-value \<0.05 will be considered statistically significant.