Optimal Target Low-density Lipoprotein Cholesterol Level for Small Vessel Occlusion Stroke

NCT ID: NCT06649240

Last Updated: 2025-05-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

4016 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-04

Study Completion Date

2030-09-30

Brief Summary

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Lipid-lowering therapy constitutes a cornerstone of secondary prevention in ischemic stroke; however, current stroke guidelines remain deficient in providing optimal target low-density lipoprotein (LDL)-cholesterol levels tailored to the stroke subtypes. Most clinical trials on LDL-cholesterol management have not differentiated between stroke subtypes or have primarily focused on large artery atherosclerosis (LAA) stroke, leaving a gap in evidence for managing LDL-cholesterol in other stroke subtypes, e.g., small vessel occlusion (SVO) stroke. While hypertension is the leading risk factor for SVO strokes, the link between elevated LDL-cholesterol and SVO stroke is also recognized. Establishing optimal LDL-cholesterol targets for SVO stroke would significantly enhance secondary prevention strategies and improve patient outcome. Thus, the investigators aim to compare intensive versus standard lipid-lowering in patients with SVO stroke. SVO70 is a multicenter, prospective, randomized, open, blinded-endpoint clinical trial. Adult participants with objectively confirmed SVO stroke within 180 days of randomization will be included. Exclusion criteria include those with predefined LDL-cholesterol targets for other conditions, statin contraindications, or women who are pregnant, breastfeeding, or planning pregnancy during the study period. Eligible participants will be randomized 1:1 to target LDL-cholesterol \<70 mg/dL (intensive group) or 90-110 mg/dL (standard group). The trial plans to enroll 4,016 participants, with the primary outcome being major adverse cardiovascular events-cardiovascular death, stroke, and acute coronary syndrome-during a follow-up period of at least 4 years. This study would provide valuable information for determining the optimal LDL-cholesterol target for patients with SVO stroke.

Detailed Description

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Conditions

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Ischemic Stroke Small Vessel Cerebrovascular Disease Cholesterol, LDL Secondary Prevention Cardiovascular Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors
Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) trial

Study Groups

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Intensive group

Target LDL-cholesterol \<70 mg/dL

Group Type EXPERIMENTAL

Statins and/or Ezetimibe

Intervention Type DRUG

Statin ± Ezetimibe to achieve target LDL-cholesterol level

PCSK9 inhibitor

Intervention Type DRUG

The use of PCSK9 inhibitors is permitted to achieve target LDL-cholesterol levels in participants who did not reach the target with statins ± ezetimibe.

Standard group

Target LDL-cholesterol 90-110 mg/dL

Group Type ACTIVE_COMPARATOR

Statins and/or Ezetimibe

Intervention Type DRUG

Statin ± Ezetimibe to achieve target LDL-cholesterol level

PCSK9 inhibitor

Intervention Type DRUG

The use of PCSK9 inhibitors is permitted to achieve target LDL-cholesterol levels in participants who did not reach the target with statins ± ezetimibe.

Interventions

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Statins and/or Ezetimibe

Statin ± Ezetimibe to achieve target LDL-cholesterol level

Intervention Type DRUG

PCSK9 inhibitor

The use of PCSK9 inhibitors is permitted to achieve target LDL-cholesterol levels in participants who did not reach the target with statins ± ezetimibe.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age 19 years or older
2. Patients with objectively confirmed small vessel occlusive infarctions in the subcortical or brainstem regions, identified through neuroimaging (MRI or CT)
3. Patients with a history of symptomatic ischemic stroke caused by the lesion described in 2), occurring within 180 days prior to enrollment
4. Patients or guardians who agree to the study protocol and sign with informed consent

Exclusion Criteria

1. Patients requiring intensive LDL cholesterol management (LDL-C \<70 mg/dL) due to another condition, with LDL cholesterol targets specified in the guidelines for that condition
2. Patients contraindicated for statin use (e.g., active liver disease, serum transaminase levels elevated more than three times the normal limit, muscle disorders, hypersensitivity to statins, or taking medications contraindicated for use with statins)
3. Women who are pregnant, breastfeeding, or intending to become pregnant during the study period
4. Deemed unsuitable for participation in the study for more than four years, as per the investigators' discretion
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hanmi Pharmaceutical co., ltd.

OTHER

Sponsor Role collaborator

Seoul National University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Seung-Hoon Lee

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Seung-Hoon Lee, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

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Korea University Ansan Hospital

Ansan, , South Korea

Site Status RECRUITING

Hallym University Sacred Heart Hospital

Anyang, , South Korea

Site Status RECRUITING

Pusan National University Hospital

Busan, , South Korea

Site Status RECRUITING

Gyeongsang National University Changwon Hospital

Changwon, , South Korea

Site Status RECRUITING

Samsung Changwon Hospital

Changwon, , South Korea

Site Status RECRUITING

Chungbuk National University Hospital

Cheongju-si, , South Korea

Site Status RECRUITING

Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, , South Korea

Site Status RECRUITING

Kangwon National University Hospital

Chuncheon, , South Korea

Site Status RECRUITING

Daegu Catholic University Medical Center

Daegu, , South Korea

Site Status RECRUITING

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Site Status RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, , South Korea

Site Status RECRUITING

Kyungpook National University Hospital

Daegu, , South Korea

Site Status RECRUITING

Chungnam National University Hospital

Daejeon, , South Korea

Site Status RECRUITING

Daejeon Eulji Medical Center

Daejeon, , South Korea

Site Status RECRUITING

Dongguk University Ilsan Hospital

Goyang, , South Korea

Site Status RECRUITING

Ilsan Paik Hospital

Goyang, , South Korea

Site Status RECRUITING

National Health Insurance Service Ilsan Hospital

Goyang, , South Korea

Site Status RECRUITING

Hanyang University Guri Hospital

Guri-si, , South Korea

Site Status RECRUITING

Chonnam National University Hospital

Gwangju, , South Korea

Site Status RECRUITING

Chosun University Hospital

Gwangju, , South Korea

Site Status RECRUITING

Chung-Ang University Gwangmyeong Hospital

Gwangmyeong, , South Korea

Site Status RECRUITING

Dongtan Sacred Heart Hospital

Hwaseong, , South Korea

Site Status RECRUITING

Wonkwang University Hospital

Iksan, , South Korea

Site Status RECRUITING

Gachon University Gil Medical Center

Incheon, , South Korea

Site Status RECRUITING

Inha University Hospital

Incheon, , South Korea

Site Status RECRUITING

International St. Mary's Hospital

Incheon, , South Korea

Site Status RECRUITING

Jeju National University Hospital

Jeju City, , South Korea

Site Status RECRUITING

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status NOT_YET_RECRUITING

Chung-Ang University Hospital

Seoul, , South Korea

Site Status RECRUITING

Ewha Womans University Mokdong Hospital

Seoul, , South Korea

Site Status RECRUITING

Ewha Womans University Seoul Hospital

Seoul, , South Korea

Site Status RECRUITING

Gangnam Severance Hospital

Seoul, , South Korea

Site Status RECRUITING

Hallym University Kangdong Sacred Heart Hospital

Seoul, , South Korea

Site Status RECRUITING

Hanyang University Seoul Hospital

Seoul, , South Korea

Site Status RECRUITING

Konkuk University Medical Center

Seoul, , South Korea

Site Status RECRUITING

Korea University Anam Hospital

Seoul, , South Korea

Site Status RECRUITING

Kyung Hee University Medical Center

Seoul, , South Korea

Site Status RECRUITING

National Medical Center

Seoul, , South Korea

Site Status RECRUITING

Nowon Eulji Medical Center

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Seoul Metropolitan Government-Seoul National University Boramae Medical Center

Seoul, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital

Seoul, , South Korea

Site Status RECRUITING

Yeouido St. Mary's Hospital

Seoul, , South Korea

Site Status RECRUITING

Yongin Severance Hospital

Yŏngin, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Wookjin Yang, MD, PhD

Role: CONTACT

+82-70-4352-2482

Seung-Hoon Lee, MD, PhD

Role: CONTACT

+82-2-2072-1014

References

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Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993 Jan;24(1):35-41. doi: 10.1161/01.str.24.1.35.

Reference Type BACKGROUND
PMID: 7678184 (View on PubMed)

Amarenco P, Benavente O, Goldstein LB, Callahan A 3rd, Sillesen H, Hennerici MG, Gilbert S, Rudolph AE, Simunovic L, Zivin JA, Welch KM; Stroke Prevention by Aggressive Reduction in Cholesterol Levels Investigators. Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes. Stroke. 2009 Apr;40(4):1405-9. doi: 10.1161/STROKEAHA.108.534107. Epub 2009 Feb 19.

Reference Type BACKGROUND
PMID: 19228842 (View on PubMed)

Duering M, Biessels GJ, Brodtmann A, Chen C, Cordonnier C, de Leeuw FE, Debette S, Frayne R, Jouvent E, Rost NS, Ter Telgte A, Al-Shahi Salman R, Backes WH, Bae HJ, Brown R, Chabriat H, De Luca A, deCarli C, Dewenter A, Doubal FN, Ewers M, Field TS, Ganesh A, Greenberg S, Helmer KG, Hilal S, Jochems ACC, Jokinen H, Kuijf H, Lam BYK, Lebenberg J, MacIntosh BJ, Maillard P, Mok VCT, Pantoni L, Rudilosso S, Satizabal CL, Schirmer MD, Schmidt R, Smith C, Staals J, Thrippleton MJ, van Veluw SJ, Vemuri P, Wang Y, Werring D, Zedde M, Akinyemi RO, Del Brutto OH, Markus HS, Zhu YC, Smith EE, Dichgans M, Wardlaw JM. Neuroimaging standards for research into small vessel disease-advances since 2013. Lancet Neurol. 2023 Jul;22(7):602-618. doi: 10.1016/S1474-4422(23)00131-X. Epub 2023 May 23.

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PMID: 37236211 (View on PubMed)

Goldstein LB, Amarenco P, Szarek M, Callahan A 3rd, Hennerici M, Sillesen H, Zivin JA, Welch KM; SPARCL Investigators. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology. 2008 Jun 10;70(24 Pt 2):2364-70. doi: 10.1212/01.wnl.0000296277.63350.77. Epub 2007 Dec 12.

Reference Type BACKGROUND
PMID: 18077795 (View on PubMed)

Mok V, Kim JS. Prevention and Management of Cerebral Small Vessel Disease. J Stroke. 2015 May;17(2):111-22. doi: 10.5853/jos.2015.17.2.111. Epub 2015 May 29.

Reference Type BACKGROUND
PMID: 26060798 (View on PubMed)

Hosomi N, Nagai Y, Kohriyama T, Ohtsuki T, Aoki S, Nezu T, Maruyama H, Sunami N, Yokota C, Kitagawa K, Terayama Y, Takagi M, Ibayashi S, Nakamura M, Origasa H, Fukushima M, Mori E, Minematsu K, Uchiyama S, Shinohara Y, Yamaguchi T, Matsumoto M; J-STARS Collaborators. The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study. EBioMedicine. 2015 Aug 6;2(9):1071-8. doi: 10.1016/j.ebiom.2015.08.006. eCollection 2015 Sep.

Reference Type BACKGROUND
PMID: 26501105 (View on PubMed)

Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Wolf ME, Hennerici MG. The ASCOD phenotyping of ischemic stroke (Updated ASCO Phenotyping). Cerebrovasc Dis. 2013;36(1):1-5. doi: 10.1159/000352050. Epub 2013 Jul 30.

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PMID: 23899749 (View on PubMed)

Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Bejot Y, Cabrejo L, Cha JK, Ducrocq G, Giroud M, Guidoux C, Hobeanu C, Kim YJ, Lapergue B, Lavallee PC, Lee BC, Lee KB, Leys D, Mahagne MH, Meseguer E, Nighoghossian N, Pico F, Samson Y, Sibon I, Steg PG, Sung SM, Touboul PJ, Touze E, Varenne O, Vicaut E, Yelles N, Bruckert E; Treat Stroke to Target Investigators. A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke. N Engl J Med. 2020 Jan 2;382(1):9. doi: 10.1056/NEJMoa1910355. Epub 2019 Nov 18.

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Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC Jr, Turan TN, Williams LS. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52(7):e364-e467. doi: 10.1161/STR.0000000000000375. Epub 2021 May 24. No abstract available.

Reference Type BACKGROUND
PMID: 34024117 (View on PubMed)

Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA; Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006 Aug 10;355(6):549-59. doi: 10.1056/NEJMoa061894.

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Kim JY, Kang K, Kang J, Koo J, Kim DH, Kim BJ, Kim WJ, Kim EG, Kim JG, Kim JM, Kim JT, Kim C, Nah HW, Park KY, Park MS, Park JM, Park JH, Park TH, Park HK, Seo WK, Seo JH, Song TJ, Ahn SH, Oh MS, Oh HG, Yu S, Lee KJ, Lee KB, Lee K, Lee SH, Lee SJ, Jang MU, Chung JW, Cho YJ, Choi KH, Choi JC, Hong KS, Hwang YH, Kim SE, Lee JS, Choi J, Kim MS, Kim YJ, Seok J, Jang S, Han S, Han HW, Hong JH, Yun H, Lee J, Bae HJ. Executive Summary of Stroke Statistics in Korea 2018: A Report from the Epidemiology Research Council of the Korean Stroke Society. J Stroke. 2019 Jan;21(1):42-59. doi: 10.5853/jos.2018.03125. Epub 2018 Dec 18.

Reference Type BACKGROUND
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Other Identifiers

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KCT0009043

Identifier Type: REGISTRY

Identifier Source: secondary_id

H-2310-119-1479

Identifier Type: -

Identifier Source: org_study_id

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