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

NCT06308952 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2024SL0006
• Study Type: interventional
• Target: 354
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Atorvastatin; Intracranial aneurysm; Flow-diverter devices; Stroke

Outcome Measures

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).

  1 year

Secondary Outcomes (1)

• Safety endpoint

  1 year

Study Arms (2)

Control group

PLACEBO COMPARATOR

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

Drug: Atorvastatin 20mg

Experimental group

EXPERIMENTAL

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

Drug: Atorvastatin 20mg

Interventions

Atorvastatin 20mg DRUG

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

Control group; Experimental group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients will be excluded if they meet any of the following criteria:
• Contraindications to atorvastatin treatment or known allergy to atorvastatin;
• Pregnancy or lactation;
• Presence of other vascular lesions (coronary artery disease, abdominal aortic aneurysm, intracranial atherosclerotic stenosis, arteriovenous malformation, dural arteriovenous fistula, Moyamoya disease, etc.);
• Prolonged statin therapy (≥30 days) or prior indications for atorvastatin therapy according to the Chinese guidelines for lipid management (2023) 21;
• Ruptured aneurysms or target aneurysm received previous operative or endovascular treatment;
• 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.);
• Patients diagnosed with multiple intracranial aneurysms who require treatment for two or more intracranial aneurysms within a one-year period;
• The target aneurysm is non-saccular (dissecting, fusiform, pseudo, infectious, etc.)
• Patient was determined that intravenous general anesthesia or general anesthesia with tracheal intubation could not be tolerated.
• Unwilling to be followed up or likely to have poor treatment compliance at initial screening;
• Life expectancy less than 3 years;
• Severe neurological deficit that renders the patient unable to live independently (modified Rankin score ≥4);
• Enrollment in another trial.
• Withdrawal criteria

Sponsors & Collaborators

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

Study Sites (1)

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510280, China

RECRUITING

Related Publications (20)

• Luo B, Kang H, Zhang H, Li T, Liu J, Song D, Zhao Y, Guan S, Maimaitili A, Wang Y, Feng W, Wang Y, Wan J, Mao G, Shi H, Yang X. Pipeline Embolization device for intracranial aneurysms in a large Chinese cohort: factors related to aneurysm occlusion. Ther Adv Neurol Disord. 2020 Nov 2;13:1756286420967828. doi: 10.1177/1756286420967828. eCollection 2020.

  PMID: 33224273 BACKGROUND

• 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.

  PMID: 26590269 RESULT

• Huang C, Ma G, Tong X, Feng X, Wen Z, Huang M, Xu A, Yuan H, Shi H, Lin J, Li C, Ge R, Huang J, Peng C, Zhu Y, Wang T, Huang C, Guo Z, Liang S, Su S, Zhang X, Li X, Liu A, Duan CZ. Comparison of Pipeline embolization device versus Tubridge embolization device in unruptured intracranial aneurysms: a multicenter, propensity score matched study. J Neurointerv Surg. 2024 May 6;17(5):467-474. doi: 10.1136/jnis-2024-021623.

  PMID: 38719444 RESULT

• Hanel RA, Cortez GM, Lopes DK, Nelson PK, Siddiqui AH, Jabbour P, Mendes Pereira V, Istvan IS, Zaidat OO, Bettegowda C, Colby GP, Mokin M, Schirmer CM, Hellinger FR, Given C, Krings T, Taussky P, Toth G, Fraser JF, Chen M, Priest R, Kan P, Fiorella D, Frei D, Aagaard-Kienitz B, Diaz O, Malek AM, Cawley CM, Puri AS, Kallmes DF. Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification. J Neurointerv Surg. 2023 Mar;15(3):248-254. doi: 10.1136/neurintsurg-2021-018501. Epub 2022 Mar 15.

  PMID: 35292570 RESULT

• 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.

  PMID: 37324979 RESULT

• 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.

  PMID: 36375835 RESULT

• 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.

  PMID: 33447904 RESULT

• 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.

  PMID: 25355814 RESULT

• 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.

  PMID: 29327999 RESULT

• 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.

  PMID: 36700744 RESULT

• 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.

  PMID: 22472556 RESULT

• Wang J, Vargas J, Spiotta A, Chaudry I, Turner RD, Lena J, Turk A. Stent-assisted coiling of cerebral aneurysms: a single-center clinical and angiographic analysis. J Neurointerv Surg. 2018 Jul;10(7):687-692. doi: 10.1136/neurintsurg-2017-013272. Epub 2017 Nov 16.

  PMID: 29146831 RESULT

• 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.

  PMID: 30565953 RESULT

• Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-188. doi: 10.1093/eurheartj/ehz455. No abstract available.

  PMID: 31504418 RESULT

• Dawson LP, Lum M, Nerleker N, Nicholls SJ, Layland J. Coronary Atherosclerotic Plaque Regression: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022 Jan 4;79(1):66-82. doi: 10.1016/j.jacc.2021.10.035.

  PMID: 34991791 RESULT

• 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.

  PMID: 11498461 RESULT

• Wagner AH, Kohler T, Ruckschloss U, Just I, Hecker M. Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol. 2000 Jan;20(1):61-9. doi: 10.1161/01.atv.20.1.61.

  PMID: 10634801 RESULT

• Qiao L, Wang S, Jia Q, Bian J, Fan Y, Xu X. Clinical efficacy and safety of statin treatment after carotid artery stenting. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3110-3115. doi: 10.1080/21691401.2019.1645149.

  PMID: 31352800 RESULT

• Tentzeris I, Rohla M, Jarai R, Farhan S, Freynhofer MK, Unger G, Nurnberg M, Geppert A, Wessely E, Wojta J, Huber K. Influence of high-dose highly efficient statins on short-term mortality in patients undergoing percutaneous coronary intervention with stenting for acute coronary syndromes. Am J Cardiol. 2014 Apr 1;113(7):1099-104. doi: 10.1016/j.amjcard.2013.12.012. Epub 2014 Jan 14.

  PMID: 24462073 RESULT

• Lilja F, Wanhainen A, Mani K. Statin therapy after elective abdominal aortic aneurysm repair improves long-term survival. Br J Surg. 2024 Jan 3;111(1):znad383. doi: 10.1093/bjs/znad383.

  PMID: 38198155 RESULT

MeSH Terms

Conditions

Ischemic Stroke; Hemorrhagic Stroke; Brain Death; Intracranial Aneurysm; Stroke

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Coma; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intracranial Arterial Diseases; Aneurysm

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Chuanzhi Duan, MD

  Southern Medical University, China

  STUDY DIRECTOR

Central Study Contacts

Chuanzhi Duan, MD

CONTACT

02062782757; doctor_duanzj@163.com

Xin Feng, MD

CONTACT

13681134001; 13681134001@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The subject numbers and corresponding medication numbers are permanently identified and unique for each successfully randomized patient. If any patients who have been successfully randomized do not receive the trial medication or cannot be reassigned to others, their medication and medication numbers will be invalidated by the medication administrator. To ensure blinding during the trial execution, unblinded personnel responsible for administering and configuring the trial drug must sign a confidentiality agreement.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: The subject numbers and corresponding medication numbers are permanently identified and unique for each successfully randomized patient. If any patients who have been successfully randomized do not receive the trial medication or cannot be reassigned to others, their medication and medication numbers will be invalidated by the medication administrator. To ensure blinding during the trial execution, unblinded personnel responsible for administering and configuring the trial drug must sign a confidentiality agreement. Investigators, other blinded investigators, subjects, and sponsors will not have access to any information regarding group assignment or related documents pertaining to the trial drug.

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 13, 2024
• Study Start: July 30, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)