Using Atorvastatin to Prevent Stroke After Flow Diverter Implantation

Atorvastatin Pretreatment in Cerebrovascular Events (APICES) After Flow Diverter Implantation: Protocol of a Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

This study is testing if the cholesterol-lowering drug atorvastatin can help prevent strokes in patients who have had a flow diverter implanted for unruptured brain aneurysms.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 354 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhujiang Hospital (Academic / other)
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06308952 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of atorvastatin, a cholesterol-lowering medication, in preventing cerebrovascular events in patients with unruptured intracranial aneurysms who have undergone flow diverter implantation. The study is designed as a multicenter, randomized, double-blind, placebo-controlled trial, focusing on the incidence of adverse cerebrovascular events within one year post-implantation. Participants will receive either atorvastatin or a placebo, and their outcomes will be monitored at various intervals to assess both efficacy and safety. The trial aims to fill a gap in current guidelines regarding post-operative care for these patients.

Who should consider this trial

Good fit: Ideal candidates are males or non-pregnant women aged 18-75 with confirmed unruptured intracranial aneurysms suitable for stent treatment.

Not a fit: Patients with contraindications to atorvastatin, those with ruptured aneurysms, or those already indicated for atorvastatin treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly reduce the risk of strokes and other cerebrovascular complications in patients undergoing flow diverter implantation.

How similar studies have performed: While atorvastatin has been widely studied for cardiovascular prevention, this specific application in the context of flow diverter implantation is novel and has not been extensively tested.

Eligibility criteria

Inclusion criteria:

1. Aged 18 to 75 years old, male or non-pregnant female;
2. UIA diagnosed by CTA, MRA, or DSA;
3. Maximal aneurysmal diameter between 3 and 25mm;
4. Understands the nature of the procedure and provision of written informed consent;
5. Indications for FD implantation with or without adjunctive coiling;
6. Is willing to return to the investigational site for follow-up according to our protocol.

Exclusion criteria:

Patients will be excluded if they meet any of the following criteria:

1. Contraindications to atorvastatin treatment or known allergy to atorvastatin;
2. Pregnancy or lactation;
3. Presence of other vascular lesions (coronary artery disease, abdominal aortic aneurysm, intracranial atherosclerotic stenosis, arteriovenous malformation, dural arteriovenous fistula, Moyamoya disease, etc.);
4. Prolonged statin therapy (≥30 days) or prior indications for atorvastatin therapy according to the Chinese guidelines for lipid management (2023) 21;
5. Ruptured aneurysms or target aneurysm received previous operative or endovascular treatment;
6. Patient currently using drugs that interact with atorvastatin metabolism (including transporter inhibitors, cyclosporine, protease inhibitors, other lipid-lowering medications (such as fibrates, ezetimibe, pcsk9 inhibitor, etc.), antacids, erythromycin, cytochrome P450 enzyme, colchicine, etc.);
7. Patients diagnosed with multiple intracranial aneurysms who require treatment for two or more intracranial aneurysms within a one-year period;
8. The target aneurysm is non-saccular (dissecting, fusiform, pseudo, infectious, etc.)
9. Other situations that the researcher deems unsuitable for inclusion in the study (inability to receive anti-platelet or anticoagulant medication; allergy or contraindication for the use of FD alloy, history of life-threatening allergy to contrast dye, ect).
10. Patient was determined that intravenous general anesthesia or general anesthesia with tracheal intubation could not be tolerated.
11. Unwilling to be followed up or likely to have poor treatment compliance at initial screening;
12. Life expectancy less than 3 years;
13. Severe neurological deficit that renders the patient unable to live independently (modified Rankin score ≥4);
14. Enrollment in another trial.

Withdrawal criteria

In this trial, participants who have provided written informed consent but are unable to complete the entire study for any reason will be withdrawn. These circumstances include the following:

1. The participants voluntarily quit the trial for various reasons;
2. Occurrence of serious adverse events (SAEs). The study may be terminated by the participants, principal investigators, ethics committee, sponsor, or regulatory authorities based on ethical considerations;
3. Early termination of the process based on the investigator's judgment in order to prevent development of severe complications;
4. Significant deviation in implementation, or the subject failed to comply with the scheduled protocol;
5. Miss the follow-up due to changes in working/living places, or fortuitous accident (traffic accident, bone fracture, accidental death, ect.). Thus, close follow-up should be conducted to determine their relationship with the usage of FD and experimental drug;
6. Flawed or absence of informed consents.

Where this trial is running

Guangzhou, Guangdong

• Zhujiang Hospital of Southern Medical University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Chuanzhi Duan, MD

Conditions Cerebrovascular Event; Stent Stenosis; Ischemic Stroke; Hemorrhagic Stroke; Stent Thrombosis; Death, Brain; Endothelial Dysfunction; Atorvastatin