Statins In Intracerbral Hemorrhage

Официальное название

STATINS USE IN INTRACEREBRAL HEMORRHAGE PATIENTS

Обзор

The SATURN trial aims to determine whether continuation vs. discontinuation of statin drugs after spontaneous lobar intracerebral hemorrhage (ICH) is the best strategy; and whether the decision to continue/discontinue statins should be influenced by an individual's Apolipoprotein-E (APOE) genotype. An MRI ancillary study (SATURN MRI), in a subset of SATURN participants , will evaluate the effects of continuation vs. discontinuation of statin drugs on hemorrhagic and ischemic MRI markers of cerebral small vessel disease, and whether the presence/burden of hemorrhagic markers (i.e. cerebral microbleeds and/or cortical superficial siderosis) on baseline MRI influences the risk of ICH recurrence on/off statin therapy.

Подробное описание

SATURN is a multi-center, pragmatic, prospective, randomized, open-label, and blinded end-point assessment (PROBE) clinical trial. A total of 1,456 patients presenting within 7 days of a spontaneous lobar ICH while taking statins will be randomized to one of two treatment strategies: discontinuation vs. continuation of statin therapy (using the same agent and dose that they were using at ICH onset). Participating subjects will undergo baseline testing for APOE genotype and will be followed for 24 months to assess for the occurrence of recurrent symptomatic ICH or major adverse cerebro-/cardio-vascular events (MACCE) during the follow-up period. A subset of SATURN participants will participate in the optional MRI study, where they will undergo a baseline MRI within 7 days of randomization into SATURN and a repeat MRI at the end of the follow-up period.

Recruitment will take place at \~ 140 sites coordinated through the NIH/NINDS StrokeNet and the Canadian Stroke Consortium.

Вмешательства

• Препарат Statins
  Statin drugs (already prescribed) at ICH onset will be either continued or discontinued by the participants following qualifying ICH

Первичные конечные точки

• Recurrent symptomatic ICH [Срок оценки: within 24 months]

Вторичные конечные точки (1)

• Major Adverse Cerebro- and Cardio-Vascular Events [Срок оценки: Within 24 months]

Критерии участия

Критерии включения

• Age ≥ 50 years.
• Spontaneous lobar ICH confirmed by CT or MRI scan
• Patient was taking a statin drug at the onset of the qualifying/index ICH
• Randomization can be carried out within 7 days of the onset of the qualifying ICH
• Patient or legally authorized representative, after consultation with the statin prescriber, agrees to be randomized to statin continuation (restart) vs. discontinuation

Критерии исключения

• Suspected secondary cause for the qualifying ICH, such as an underlying vascular abnormality or tumor, trauma, venous infarction, or hemorrhagic transformation of an ischemic infarct.
• History of recent myocardial infarction (attributed to coronary artery disease) or unstable angina within the previous 3 months
• Diabetic patients with history of myocardial infarction or coronary revascularization
• History of familial hypercholesterolemia
• Patients receiving proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors
• Known diagnosis of severe dementia
• Inability to obtain informed consent
• Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, or other obvious reasons for noncompliance, such as unable to adhere to the protocol specified visits/assessments.
• Life expectancy of less than 24 months due to co-morbid terminal conditions.
• Pre-morbid mRS >3
• ICH score >3 upon presentation.
• Contraindications to continuation/resumption of statin therapy, such as significant elevations of serum creatinine kinase and/or liver transaminases, and rhabdomyolysis
• Woman of childbearing potential
• Concurrent participation in another research protocol for investigation of experimental therapy.
• Indication that withdrawal of care will be implemented for the qualifying ICH.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• Beth Israel Deaconess Medical Center — Boston

Публикации

• Marchina S, Yeatts SD, Foster LD, Janis S, Shoamanesh A, Khatri P, Bernstein K, Perlmutter A, Stever C, Heistand EC, Broderick JP, Greenberg SM, Leira EC, Rosand J, Lioutas VA, Salman RAS, Tirschwell D, Marti-Fabregas J, Selim M. Rationale and Design of the Statin Use in Intracerebral Hemorrhage Patients (SATURN) Trial. Cerebrovasc Dis. 2025;54(2):270-277. doi: 10.1159/000538195. Epub 2024 Mar 16. PMID 38493765
• Marchina S, Foster LD, Yeatts SD, Khatri P, Bernstein K, Perlmutter A, Heistand EC, Smith EE, Sharma M, Broderick JP, Lioutas VA, Marti-Fabregas J, Selim M, Shoamanesh A. SATURN MRI: study protocol for the statin use in intracerebral hemorrhage patients MRI ancillary study. Trials. 2025 Aug 30;26(1):323. doi: 10.1186/s13063-025-09024-0. PMID 40886018
• Zhao W, Yeatts SD, Broderick JP, Selim MH, Adeoye OM, Durkalski-Mauldin VL, Meinzer CN, Martin RH, Dillon CR, Cassarly CN, Pauls KH, Elm JJ. Optimal Randomization Designs for Large Multicenter Clinical Trials: From the National Institutes of Health Stroke Trials Network Funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke Experience. Stroke. 2023 Jul;54(7 PMID 37078281
• Lee TC, Leung WC, Ho C, Chiu MW, Leung IY, Wong YK, Roxanna LK, Sum CH, Lui DT, Cheung RT, Leung GK, Chan KH, Teo KC, Lau KK. Association of LDL-cholesterol <1.8 mmol/L and statin use with the recurrence of intracerebral hemorrhage. Int J Stroke. 2024 Jul;19(6):695-704. doi: 10.1177/17474930241239523. Epub 2024 Mar 23. PMID 38429252
• Szejko N, Kirsch E, Falcone GJ. Genetic determinants of LDL cholesterol and risk of intracerebral haemorrhage. Curr Opin Lipidol. 2021 Aug 1;32(4):244-248. doi: 10.1097/MOL.0000000000000761. PMID 34010223

Идентификаторы

NCT: NCT03936361 · 2018C000515

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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