Statin Therapy for patients with compensated Cirrhosis

他汀类药物治疗代偿性肝硬化患者

• 批准号: 10491758
• 负责人: Neehar Dilip Parikh
• 金额: $ 64.16万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10491758
• 关键词: Address; Adverse event; Alcohol abuse; Alcohols; American; Attention; Biological Markers; Blood; Cardiovascular system; Caregivers; Caring; Cessation of life; Child; Cicatrix; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Collection; Complex; Complication; Computerized Medical Record; Conflict (Psychology); Data; Data Collection; Data Coordinating Center; Development; Discrimination; Disease; Disease Progression; Distress; Dyslipidemias; Enrollment; Epidemiology; Etiology; Event; Exclusion Criteria; Fibrosis; Funding; Health Care Costs; Heart Diseases; Hepatic; Hepatic Encephalopathy; Hepatology; High Prevalence; Hypertension; Incidence; Individual; Laboratories; Link; Lipids; Liver; Liver Fibrosis; Liver diseases; Longitudinal cohort; Measurement; Measures; Medical; Medicare; Mental Depression; Metabolic; Methods; Michigan; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Observational Study; Outcome; Pathway interactions; Patient Outcomes Assessments; Patient risk; Patients; Placebo Control; Portal Hypertension; Positioning Attribute; Prevalence; Prevention therapy; Primary carcinoma of the liver cells; Provider; Quality of life; Randomized; Research Infrastructure; Resources; Risk; Role; Site; Stratification; Symptoms; Systemic blood pressure; Therapy trial; Twin Multiple Birth; United States; Universities; Vasodilation; Viral; Woman; Work; alcohol use disorder; associated symptom; base; cardiovascular risk factor; clinical practice; clinical risk; cohort; disability; disabling symptom; effective therapy; elastography; epidemiology study; experience; falls; frailty; high risk; hospital readmission; improved; inclusion criteria; indexing; innovative technologies; liver transplantation; mortality; novel; outcome prediction; patient population; predictive modeling; prevent; primary outcome; prognostic; prognostic index; prognostic model; prognostic value; programs; prospective; randomized placebo controlled trial; recruit; response; risk prediction; risk stratification; secondary outcome; tool; trial design

Project Abstract Cirrhosis is a highly morbid and resource intensive condition that afflicts an increasing number of individuals in the US. The epidemiology of cirrhosis, however is changing, with demographic shifts and increasing prevalence of metabolic and alcohol associated liver disease. We lack sufficient tools for risk stratification of the changing population of patients with cirrhosis, as our current prognostic models for compensated cirrhosis lack adequate discrimination. Furthermore, patients with cirrhosis have symptoms and quality of life deficits that are not routinely addressed in clinical practice. Patient reported outcomes (PROs) can be incorporated into risk models with excellent prognostic discrimination. Patients with cirrhosis have a risk of deadly complications such as hepatic decompensation or hepatocellular carcinoma, however we lack disease modifying agents that can forestall the development of these complication. Several epidemiological studies suggest statins may be associated with a decreased risk of cirrhosis related decompensation, however we lack prospective data to support its use for this indication. In Aim 1 of this proposal, as part of a multicenter consortium, we aim to recruit a large contemporary longitudinal cohort of patients with compensated cirrhosis from our Hepatology practice at the University of Michigan, which follows over 1,900 patients with cirrhosis longitudinally. We will perform serial measurements of clinical, liver fibrosis, PRO, functional, and laboratory parameters over the study period. As part of the PRO measurement, will develop automated alerts with care pathways within the electronic medical record to alert providers for alcohol use disorder in patients enrolled in the cohort. In Aim 2, we will develop and validate multidimensional risk models, incorporating the longitudinal parameters measured in Aim 1, in order to predict outcomes, including survival, hepatic decompensation, cardiovascular events, and disability. In Aim 3 we will perform a randomized placebo control trial of statins in patients with compensated cirrhosis. The primary outcome will be overall survival, with secondary outcomes of hepatic decompensation/hepatocellular carcinoma development and cardiovascular events. We will perform additional exploratory analyses to determine the impact of statins on fibrosis progression. This proposal will provide critical information that will have profound clinical impact on the management of patients with cirrhosis. We are well positioned to conduct this study given our Hepatology and clinical research infrastructure.

项目摘要 肝硬化是一种发病率很高且资源密集型的疾病，困扰着越来越多的人 美国。然而，随着人口结构的变化和人口的增加，肝硬化的流行病学正在发生变化。 代谢性和酒精相关性肝病的患病率。我们缺乏足够的工具来进行风险分层 肝硬化患者群体的变化，作为我们目前代偿性肝硬化的预后模型 缺乏足够的歧视。此外，肝硬化患者有症状和生活质量下降 临床实践中不常规解决的问题。患者报告的结果 (PRO) 可以纳入 具有出色预后辨别能力的风险模型。肝硬化患者有致命并发症的风险 例如肝功能失代偿或肝细胞癌，但是我们缺乏能够改变疾病的药物 可以预防这些并发症的发展。多项流行病学研究表明他汀类药物可能 与肝硬化相关失代偿风险降低相关，但是我们缺乏前瞻性数据 支持其用于该适应症。在本提案的目标 1 中，作为多中心联盟的一部分，我们的目标是 从我们的肝病科招募了一大批当代代偿性肝硬化患者的纵向队列 密歇根大学对 1,900 多名肝硬化患者进行了纵向跟踪。我们将 对临床、肝纤维化、PRO、功能和实验室参数进行连续测量 学习期间。作为 PRO 测量的一部分，将开发包含护理路径的自动警报 电子病历提醒提供者该队列中患者的酒精使用障碍。在目标 2 中， 我们将开发和验证多维风险模型，结合测量的纵向参数 在目标 1 中，为了预测结果，包括生存、肝代偿失调、心血管事件和 残疾。在目标 3 中，我们将对补偿性患者进行他汀类药物的随机安慰剂对照试验。 肝硬化。主要结局是总生存期，次要结局是肝脏疾病 失代偿/肝细胞癌的发展和心血管事件。我们将进行额外的 探索性分析以确定他汀类药物对纤维化进展的影响。该提案将提供 将对肝硬化患者的治疗产生深远临床影响的关键信息。我们是 鉴于我们的肝病学和临床研究基础设施，我们有能力开展这项研究。