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RecruitingNCT06308952Updated Mar 3, 2026

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

A Phase 4 interventional study of Atorvastatin 20mg in Cerebrovascular Event, Stent Stenosis and Ischemic Stroke, sponsored by Duan Chuanzhi. Recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-03-03.

Sponsored by Duan Chuanzhi · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
354
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Cerebrovascular Event
  • Stent Stenosis
  • Ischemic Stroke
  • Hemorrhagic Stroke
  • Stent Thrombosis
  • Death, Brain
  • Endothelial Dysfunction

Keywords

  • Atorvastatin
  • Intracranial aneurysm
  • Flow-diverter devices
  • Stroke
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
354 participants (estimated)

Study arms

  • Placebo comparator
    Control group

    placebo (composed mainly of starch, Frontage Pharma, Jiangsu, China) 20mg orally once daily for 180 days

    Drug: Atorvastatin 20mg

  • Experimental
    Experimental group

    atorvastatin (Pfizer, New York, USA) 20mg orally once daily for 180 days

    Drug: Atorvastatin 20mg

Interventions

  • DrugAtorvastatin 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).

    Also known as: Lipitor

05

What researchers measure

Primary outcomes

  1. Efficacy endopoint

    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).

    Time frame: 1 year

Secondary outcomes

  1. Safety endpoint

    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.

    Time frame: 1 year

06

Study locations

1 of 1 sites recruiting
  • Zhujiang Hospital of Southern Medical University
    Guangzhou, Guangdong 510280, China
    Recruiting
07

References and documents

Publications

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  • Vergouwen MD, Jong-Tjien-Fa AV, Algra A, Rinkel GJ. Time trends in causes of death after aneurysmal subarachnoid hemorrhage: A hospital-based study. Neurology. 2016 Jan 5;86(1):59-63. doi: 10.1212/WNL.0000000000002239. Epub 2015 Nov 20. PubMed 26590269 ↗
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  • Qi P, Tong X, Liang X, Xue X, Wu Z, Feng X, Zhang M, Jiang Z, Wang D, Liu A. Flow diversion for posterior circulation aneurysms: a multicenter retrospective study. Ther Adv Neurol Disord. 2023 Jun 8;16:17562864231176187. doi: 10.1177/17562864231176187. eCollection 2023. PubMed 37324979 ↗
  • Hanel RA, Cortez GM, Coon AL, Kan P, Taussky P, Wakhloo AK, Welch BG, Dogan A, Bain M, De Vries J, Ebersole K, Meyers PM; SCENT Investigator Group. Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide-Neck Aneurysms - SCENT: 3-year outcomes. J Neurointerv Surg. 2023 Nov;15(11):1084-1089. doi: 10.1136/jnis-2022-019512. Epub 2022 Nov 14. PubMed 36375835 ↗
  • Kang H, Zhou Y, Luo B, Lv N, Zhang H, Li T, Song D, Zhao Y, Guan S, Maimaitili A, Wang Y, Feng W, Wang Y, Wan J, Mao G, Shi H, Yang X, Liu J. Pipeline Embolization Device for Intracranial Aneurysms in a Large Chinese Cohort: Complication Risk Factor Analysis. Neurotherapeutics. 2021 Apr;18(2):1198-1206. doi: 10.1007/s13311-020-00990-8. Epub 2021 Jan 14. PubMed 33447904 ↗
  • Kallmes DF, Hanel R, Lopes D, Boccardi E, Bonafe A, Cekirge S, Fiorella D, Jabbour P, Levy E, McDougall C, Siddiqui A, Szikora I, Woo H, Albuquerque F, Bozorgchami H, Dashti SR, Delgado Almandoz JE, Kelly ME, Turner R 4th, Woodward BK, Brinjikji W, Lanzino G, Lylyk P. International retrospective study of the pipeline embolization device: a multicenter aneurysm treatment study. AJNR Am J Neuroradiol. 2015 Jan;36(1):108-15. doi: 10.3174/ajnr.A4111. Epub 2014 Oct 29. PubMed 25355814 ↗
  • Colby GP, Bender MT, Lin LM, Beaty N, Caplan JM, Jiang B, Westbroek EM, Varjavand B, Campos JK, Huang J, Tamargo RJ, Coon AL. Declining complication rates with flow diversion of anterior circulation aneurysms after introduction of the Pipeline Flex: analysis of a single-institution series of 568 cases. J Neurosurg. 2018 Dec 1;129(6):1475-1481. doi: 10.3171/2017.7.JNS171289. Epub 2018 Jan 12. PubMed 29327999 ↗
  • Zhang H, Zhang H, Liu J, Song D, Zhao Y, Guan S, Maimaitili A, Wang Y, Feng W, Wang Y, Wan J, Mao G, Shi H, Luo B, Shao Q, Chang K, Zhang Q, He Y, Zhang P, Yang X, Li L, Li TX. Pipeline Embolization Device for Small and Medium Vertebral Artery Aneurysms: A Multicenter Study. Neurosurgery. 2023 May 1;92(5):971-978. doi: 10.1227/neu.0000000000002319. Epub 2022 Dec 29. PubMed 36700744 ↗
  • Fargen KM, Hoh BL, Welch BG, Pride GL, Lanzino G, Boulos AS, Carpenter JS, Rai A, Veznedaroglu E, Ringer A, Rodriguez-Mercado R, Kan P, Siddiqui A, Levy EI, Mocco J. Long-term results of enterprise stent-assisted coiling of cerebral aneurysms. Neurosurgery. 2012 Aug;71(2):239-44; discussion 244. doi: 10.1227/NEU.0b013e3182571953. PubMed 22472556 ↗
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  • Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1046-e1081. doi: 10.1161/CIR.0000000000000624. Epub 2018 Nov 10. No abstract available. PubMed 30565953 ↗
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  • Diomede L, Albani D, Sottocorno M, Donati MB, Bianchi M, Fruscella P, Salmona M. In vivo anti-inflammatory effect of statins is mediated by nonsterol mevalonate products. Arterioscler Thromb Vasc Biol. 2001 Aug;21(8):1327-32. doi: 10.1161/hq0801.094222. PubMed 11498461 ↗
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Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT06308952
Lead sponsor
Duan Chuanzhi
Collaborators
Shenzhen Second People's Hospital, First Affiliated Hospital of Harbin Medical University, ZhuHai Hospital, First Hospital of Shijiazhuang City, Eighth Affiliated Hospital, Sun Yat-sen University, First Affiliated Hospital of Jinan University, Dongguan Kanghua Hospital, Beijing Tiantan Hospital, Guangdong 999 Brain Hospital, The First Affiliated Hospital of Zhengzhou University, First Affiliated Hospital of Chongqing Medical University, Dongguan People's Hospital, Xinqiao Hospital of Chongqing, Shanxi Cardiovascular Hospital, Peking Union Medical College Hospital, Tianjin Huanhu Hospital
Responsible party
Duan Chuanzhi (Professor, Zhujiang Hospital) — Sponsor-investigator
First posted
Mar 13, 2024
Start date
Jul 30, 2024
Primary completion
Dec 1, 2027 (estimated)
Completion
Dec 31, 2027 (estimated)
Last update
Mar 3, 2026

Study contacts

Chuanzhi Duan, MD
Contact
doctor_duanzj@163.com
02062782757
Xin Feng, MD
Contact
13681134001@163.com
13681134001
Chuanzhi Duan, MD
study director · Southern Medical University, China

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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