Atorvastatin Pretreatment in Cerebrovascular Events (APICES) After Flow Diverter Implantation

February 27, 2026 updated by: Duan Chuanzhi

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

APICES trial is an investigator-initiated, multicenter, multicenter, randomized, double-blind, placebo-controlled clinical trial that plans to enroll 396 patients with a 1-year follow-up, including a neurovascular imaging examination [digital subtraction angiography (DSA), CT angiography (CTA) or magnetic resonance angiography (MRA)] at 6 months after index treatment. It was designed in compliance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The study was approved by the Ethics Committee of Zhujiang Hospital of South Medical University (2024-KY-032-02) and registered at ClinicalTrials.gov (NCT06308952). The participants will be recruited from twelve advanced stroke centers in China.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Aneurysmal subarachnoid hemorrhage (aSAH) is a disastrous subtype of stroke, which is associated with high mortality and morbidity. With the advancement of endovascular techniques, flow diverter (FD) devices have emerged as a preventive treatment for unruptured intracranial aneurysms (UIAs). Although a series of studies have demonstrated that FDs can achieve high rates of aneurysmal occlusion, the safety of FDs remains a concern, with a non-negligible risk of complications (5%-12%). Furthermore, previously published studies have also confirmed that FDs have a significantly higher rate of in-stent stenosis (ISS) compared with conventional stents, which remains a clinical issue requiring attention and resolution. However, there are currently no guideline recommendations or clinical evidence available on how to prevent complications in patients with IA after undergoing FD implantation, apart from conventional dual antiplatelet therapy.

Elevated low-density lipoprotein cholesterol (LDLC) levels increase the risk of vascular events. Lipid-lowing treatment with β-Hydroxy β-methylglutaryl-CoA reductase inhibitors (such as statins) is a cornerstone in avoiding such events. Several studies indicate that the advantages of statins could surpass their traditional role in lowering cholesterol levels, encompassing a range of additional benefits known as pleiotropic effects. Those multiple effects include anti-inflammatory function, vasodilation, anticoagulation, platelet inhibition, and antioxidants. Although the clinical benefit of statin pretreatment has been clarified in carotid artery stenting, percutaneous coronary intervention, and abdominal aortic aneurysm repair, its effect on endovascular treatment of UIAs remains unclear.

Due to the pleiotropic benefits beyond lipid lowering, the effect of statin pretreatment may theoretically contribute to the reduction of cerebrovascular events after FD implantation. Nevertheless, there is currently a lack of high-quality clinical evidence supporting this hypothesis. Thus, we designed the atorvastatin pretreatment in cerebrovascular events (APICES) randomized controlled trial (RCT) to explore whether statin pretreatment is superior to placebo in patients undergoing FD treatment for UIAs.

Study Type

Interventional

Enrollment (Estimated)

354

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510280
        • Recruiting
        • Zhujiang Hospital of Southern Medical University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control group
placebo (composed mainly of starch, Frontage Pharma, Jiangsu, China) 20mg orally once daily for 180 days
Drug: Atorvastatin 20mg
Eligible subjects screened will enter the pretreatment period (at least 24 hours) and be randomly assigned to the trial group (oral atorvastatin) or the control group (placebo) to start receiving the trial drug (20mg, qd). Additionally, the patient was started on basic dual anti-platelet (aspirin 75mg qd + clopidogrel 75mg qd/ticagrelor 45mg bid).
Other Names:
  • Lipitor
Experimental: Experimental group
atorvastatin (Pfizer, New York, USA) 20mg orally once daily for 180 days
Drug: Atorvastatin 20mg
Eligible subjects screened will enter the pretreatment period (at least 24 hours) and be randomly assigned to the trial group (oral atorvastatin) or the control group (placebo) to start receiving the trial drug (20mg, qd). Additionally, the patient was started on basic dual anti-platelet (aspirin 75mg qd + clopidogrel 75mg qd/ticagrelor 45mg bid).
Other Names:
  • Lipitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy endopoint
Time Frame: 1 year

Patients without new-onset cerebrovascular events within 12 months:

  1. Any documented stroke (clinical and imaging): hemorrhage stroke (any intracranial hemorrhage subtype confirmed by CT scan) or ischemic stroke (neurological dysfunction more than 24 hours after onset or new acute cerebral infarction lesion confirmed by imaging);
  2. the incidence of significant in-stent stenosis (a narrowing of the FD diameter exceeding 50% without pre-existing significant artery stenosis detected by 12-month angiographic follow-up).
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety endpoint
Time Frame: 1 year
  1. muscle-related adverse events (excluding those due to exercise or trauma);
  2. digestive system adverse events (dyspepsia, unexplained abdominal pain, biliary colic, gastrointestinal bleeding);
  3. Newly diagnosed cancer, diabetes, neurocognitive disorders, cataracts;
  4. all-caused death;
  5. the incidence and the degree of ISS;
  6. incomplete aneurysm occlusion;
  7. new-onset in-stent thrombosis.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duan Chuanzhi

Collaborators

Peking Union Medical College Hospital
Beijing Tiantan Hospital
The First Affiliated Hospital of Zhengzhou University
First Affiliated Hospital of Jinan University
Xinqiao Hospital of Chongqing
Shenzhen Second People's Hospital
Dongguan People's Hospital
First Hospital of Shijiazhuang City
First Affiliated Hospital of Chongqing Medical University
First Affiliated Hospital of Harbin Medical University
Guangdong 999 Brain Hospital
Shanxi Cardiovascular Hospital
ZhuHai Hospital
Dongguan Kanghua Hospital
Tianjin Huanhu Hospital
Eighth Affiliated Hospital, Sun Yat-sen University

Investigators

  • Study Director: Chuanzhi Duan, MD, Southern Medical University, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2024

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

March 5, 2024

First Submitted That Met QC Criteria

March 5, 2024

First Posted (Actual)

March 13, 2024

Study Record Updates

Last Update Posted (Actual)

March 3, 2026

Last Update Submitted That Met QC Criteria

February 27, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024SL0006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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