Clinical trial NCT06649240: Optimal Target Low-density Lipoprotein Cholesterol Level for Small Vessel Occlusion Stroke
Official title: Optimal Target Low-density Lipoprotein Cholesterol Level for Small Vessel Occlusion Stroke (SVO70)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Hanmi Pharmaceutical co., ltd.
First posted: 2024-10-18
Enrollment: 4016
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Major adverse cardiovascular event
timeFrame: 4 years
Secondary outcomes:
measure: Any stroke
timeFrame: 4 years
measure: Ischemic stroke or transient ischemic attack
timeFrame: 4 years
measure: Cardiovascular death
timeFrame: 4 years
measure: Myocardial infarction
timeFrame: 4 years
measure: Any death
timeFrame: 4 years
measure: Acute coronary syndrome
timeFrame: 4 years
Other outcomes:
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Anyang
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Changwon
country: Korea, Republic of
facility: Gyeongsang National University Changwon Hospital
city: Changwon
country: Korea, Republic of
facility: Samsung Changwon Hospital
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Chuncheon
country: Korea, Republic of
facility: Hallym University Chuncheon Sacred Heart Hospital
city: Chuncheon
country: Korea, Republic of
facility: Kangwon National University Hospital
city: Daegu
country: Korea, Republic of
facility: Daegu Catholic University Medical Center
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Daejeon Eulji Medical Center
city: Goyang
country: Korea, Republic of
facility: Dongguk University Ilsan Hospital
city: Goyang
country: Korea, Republic of
facility: Ilsan Paik Hospital
city: Goyang
country: Korea, Republic of
facility: National Health Insurance Service Ilsan Hospital
city: Guri
country: Korea, Republic of
facility: Hanyang University Guri Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chosun University Hospital
city: Gwangmyeong
country: Korea, Republic of
facility: Chung-Ang University Gwangmyeong Hospital
city: Hwaseong
country: Korea, Republic of
facility: Dongtan Sacred Heart Hospital
city: Iksan
country: Korea, Republic of
facility: Wonkwang University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Incheon
country: Korea, Republic of
facility: International St. Mary's Hospital
city: Jeju
country: Korea, Republic of
facility: Jeju National University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Hallym University Kangdong Sacred Heart Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Medical Center
city: Seoul
country: Korea, Republic of
facility: National Medical Center
city: Seoul
country: Korea, Republic of
facility: Nowon Eulji Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul Metropolitan Government-Seoul National University Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Yeouido St. Mary's Hospital
city: Yongin
country: Korea, Republic of
facility: Yongin Severance Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Seung-Hoon Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.