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Cerebrovascular EventPhase 4NCT06308952

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

A Phase 4 study testing Atorvastatin 20mg in people with Cerebrovascular Event and Stent Stenosis, run by Duan Chuanzhi at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Atorvastatin 20mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
354 participants
Where
1 siteChina
Study dates
30 Jul 2024to 31 Dec 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 23Show fewer
  • 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.)
  • 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).
  • 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
  • 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:
  • The participants voluntarily quit the trial for various reasons;
  • 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;
  • Early termination of the process based on the investigator's judgment in order to prevent development of severe complications;
  • Significant deviation in implementation, or the subject failed to comply with the scheduled protocol;
  • 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;
  • Flawed or absence of informed consents.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Chuanzhi Duan, MD contact

02062782757

doctor_duanzj@163.com

Xin Feng, MD contact

13681134001

13681134001@163.com

China1 site, 1 recruiting

  • Zhujiang Hospital of Southern Medical University

    Guangzhou, Guangdong, 510280

    Chuanzhi Duan, MD, 02062782757, doctor_duanzj@163.com

    Xin Feng, MD, 13681134001, 13681134001@163.com

    Recruiting

Other trials in China

About this study

Official title: 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.

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.

Being tested
Atorvastatin 20mg
Keywords
Atorvastatin, Intracranial aneurysm, Flow-diverter devices, Stroke
Medical subject headings
Ischemic Stroke, Hemorrhagic Stroke, Brain Death, Intracranial Aneurysm, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atorvastatin 20mgDrug

    Also called Lipitor

    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).

Study groups in NCT06308952
Study groupRoleWhat they receive
Control groupPlacebo comparatorplacebo (composed mainly of starch, Frontage Pharma, Jiangsu, China) 20mg orally once daily for 180 days
Receives: Drug: Atorvastatin 20mg
Experimental groupExperimentalatorvastatin (Pfizer, New York, USA) 20mg orally once daily for 180 days
Receives: Drug: Atorvastatin 20mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 1 year

Secondary outcomes (1)

  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.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2024
  2. Study start30 Jul 2024
  3. Primary completion1 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
354 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06308952
Sponsor's protocol ID
2024SL0006
Status last verified
Feb 2026
First submitted
5 Mar 2024
Last updated
3 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33224273

  • 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

  • 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.

    PubMed 38719444

  • 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.

    PubMed 35292570

  • 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

  • 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.

    PubMed 29146831

  • 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

  • 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.

    PubMed 31504418

  • 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.

    PubMed 34991791

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Atorvastatin 20mg in people with Cerebrovascular Event and Stent Stenosis, run by Duan Chuanzhi at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Chuanzhi Duan, MD (02062782757, doctor_duanzj@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy endopoint (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06308952, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2026.

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