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

NCT06649240 | Recruiting DMC

• 2 other identifiers: H-2310-119-1479KCT0009043
• Study Type: interventional
• Target: 4,016
• Locations: 1 country
• Sites: 46

Brief Summary

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.

Conditions

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

Keywords

Cerebral Small Vessel Diseases; Ischemic Stroke; Secondary Prevention; Cholesterol, LDL; Statins

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiovascular event

  Major adverse cardiovascular event (MACE) includes cardiovascular death, stroke, and acute coronoary syndrome (i.e., ST-elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina).

  4 years

Secondary Outcomes (6)

• Any stroke

  4 years

• Ischemic stroke or transient ischemic attack

  4 years

• Cardiovascular death

  4 years

• Myocardial infarction

  4 years

• Any death

  4 years

Study Arms (2)

Intensive group

EXPERIMENTAL

Target LDL-cholesterol \<70 mg/dL

Drug: Statins and/or Ezetimibe; Drug: PCSK9 inhibitor

Standard group

ACTIVE COMPARATOR

Target LDL-cholesterol 90-110 mg/dL

Drug: Statins and/or Ezetimibe; Drug: PCSK9 inhibitor

Interventions

Statins and/or Ezetimibe DRUG

Statin ± Ezetimibe to achieve target LDL-cholesterol level

Intensive group; Standard group

PCSK9 inhibitor 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.

Intensive group; Standard group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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)
• Women who are pregnant, breastfeeding, or intending to become pregnant during the study period
• Deemed unsuitable for participation in the study for more than four years, as per the investigators' discretion

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Hanmi Pharmaceutical co., ltd.: collaborator

Study Sites (46)

Korea University Ansan Hospital

Ansan, South Korea

RECRUITING

Hallym University Sacred Heart Hospital

Anyang, South Korea

RECRUITING

Pusan National University Hospital

Busan, South Korea

RECRUITING

Gyeongsang National University Changwon Hospital

Changwon, South Korea

RECRUITING

Samsung Changwon Hospital

Changwon, South Korea

RECRUITING

Chungbuk National University Hospital

Cheongju-si, South Korea

RECRUITING

Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, South Korea

RECRUITING

Kangwon National University Hospital

Chuncheon, South Korea

RECRUITING

Daegu Catholic University Medical Center

Daegu, South Korea

RECRUITING

Keimyung University Dongsan Medical Center

Daegu, South Korea

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, South Korea

RECRUITING

Kyungpook National University Hospital

Daegu, South Korea

RECRUITING

Chungnam National University Hospital

Daejeon, South Korea

RECRUITING

Daejeon Eulji Medical Center

Daejeon, South Korea

RECRUITING

Dongguk University Ilsan Hospital

Goyang, South Korea

RECRUITING

Ilsan Paik Hospital

Goyang, South Korea

RECRUITING

National Health Insurance Service Ilsan Hospital

Goyang, South Korea

RECRUITING

Hanyang University Guri Hospital

Guri-si, South Korea

RECRUITING

Chonnam National University Hospital

Gwangju, South Korea

RECRUITING

Chosun University Hospital

Gwangju, South Korea

RECRUITING

Chung-Ang University Gwangmyeong Hospital

Gwangmyeong, South Korea

RECRUITING

Dongtan Sacred Heart Hospital

Hwaseong, South Korea

RECRUITING

Wonkwang University Hospital

Iksan, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, South Korea

RECRUITING

Inha University Hospital

Incheon, South Korea

RECRUITING

International St. Mary's Hospital

Incheon, South Korea

RECRUITING

Jeju National University Hospital

Jeju City, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

NOT YET RECRUITING

Chung-Ang University Hospital

Seoul, South Korea

RECRUITING

Ewha Womans University Mokdong Hospital

Seoul, South Korea

RECRUITING

Ewha Womans University Seoul Hospital

Seoul, South Korea

RECRUITING

Gangnam Severance Hospital

Seoul, South Korea

RECRUITING

Hallym University Kangdong Sacred Heart Hospital

Seoul, South Korea

RECRUITING

Hanyang University Seoul Hospital

Seoul, South Korea

RECRUITING

Konkuk University Medical Center

Seoul, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, South Korea

RECRUITING

Kyung Hee University Medical Center

Seoul, South Korea

RECRUITING

National Medical Center

Seoul, South Korea

RECRUITING

Nowon Eulji Medical Center

Seoul, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Seoul Metropolitan Government-Seoul National University Boramae Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Severance Hospital

Seoul, South Korea

RECRUITING

Yeouido St. Mary's Hospital

Seoul, South Korea

RECRUITING

Yongin Severance Hospital

Yŏngin, South Korea

RECRUITING

Related Publications (11)

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• 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.

  PMID: 19228842 BACKGROUND

• 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.

  PMID: 37236211 BACKGROUND

• 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.

  PMID: 18077795 BACKGROUND

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  PMID: 26060798 BACKGROUND

• 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.

  PMID: 26501105 BACKGROUND

• 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.

  PMID: 23899749 BACKGROUND

• 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.

  PMID: 31738483 BACKGROUND

• 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.

  PMID: 34024117 BACKGROUND

• 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.

  PMID: 16899775 BACKGROUND

• 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.

  PMID: 30558400 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke; Cerebral Small Vessel Diseases; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Study Officials

• Seung-Hoon Lee, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wookjin Yang, MD, PhD

CONTACT

+82-70-4352-2482; ywj_2002@naver.com

Seung-Hoon Lee, MD, PhD

CONTACT

+82-2-2072-1014

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) trial
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 18, 2024
• Study Start: October 4, 2024
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (46)