Statins for Prevention of Disease Progression and Hospitalization in Liver Cirrhosis: A Multi-center, Randomized, Double Blind, Placebo-controlled Trial. The STATLiver Trial
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Composite endpoint of numbers of death or liver transplantation
研究概览
简要总结
In a randomized, doubleblind and placebo-controlled trial we assess both clinical and cellular effects of atorvastatin in patients with liver cirrhosis.
162 participants will be allocated to atorvastatin 10-20 mg or placebo for 18 months. Clinical outcomes of survival, hospitalizations and safety will be evaluated. Also, the trial will investigate cellular functions in the liver by mass spectrometry proteomics, and single cell transcriptomics as well as exploring atorvastatin effects on different fenotypes by metagenomics.
详细描述
Introduction Several studies have demonstrated the beneficial effects of statins in vascular and heart disease. Statins have antithrombotic effects, decrease oxidative stress and inflammation at the vessel wall, and improve endothelial dysfunction by increasing Nitric Oxide (NO) production in endothelial cells.
Statins may also inhibit fibrogenesis in cirrhotic rats. In recent years, a series of pilot studies have assessed the effects of simvastatin on portal hypertension and risk of variceal bleeding.
Only a few studies have evaluated the efficacy of statins in cirrhosis of mixed etiology and decompensated cirrhosis. High quality clinical trials have focused on the hemodynamic effects of simvastatin on portal hypertension. Evidence supporting the use of statins in a real-world clinical setting, and data on the effects on inflammation and generation of fibrosis in the liver in humans is in high demand.
Study setting The trial will take place in university hospitals with tertiary referral from other hospitals, departments and general practice. Patients referred to the outpatient clinics or hospitalized in the Gastro Unit, Amager Hvidovre Hospital (AHH) and Department of Hepatology and Gastroenterology, Aarhus University Hospital (AUH), all Denmark are eligible for inclusion.
Study Part One
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Allocation and randomisation is blinded. Participants are only identified by randomisation number (no group names) Allocation ratio is 1:1 All personnel and participants are blinded through the study period. All outcome assessors are blinded to treatment, and initial data analysis is performed blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients in the age of 18 to 80 years
- •Patients with liver cirrhosis, diagnosed by liver biopsy or ultrasound or CT scan of the liver and clinical biochemistry compatible with cirrhosis within the past 3 months.
- •In women, documented absence of pregnancy and unless in menopause commitment to use adequate contraception.
- •Clinically significant portal hypertension with a hepatic venous pressure gradient measured by liver vein catheterization >10 mmHg.
- •Ability to read and understand project information in Danish and give written, informed consent.
排除标准
- •People treated with statins within the last year.
- •People with liver cirrhosis, with a clinically verified infection (standard biochemistry, culture) within the last four weeks.
- •Pregnancy or lactation.
- •Hepatocellular carcinoma
- •HIV infection and treatment with protease inhibitors
- •People in whom the clinician and investigators may have reason to doubt compliance to trial medication
- •Clinical and biochemical signs of hepato-renal syndrome defined by current guidelines (EASL) within the last 14 days
- •A MELD score above 23, or Child-Pugh score higher than
- •Hepatic encephalopathy grade 2 or higher
研究组 & 干预措施
Atorvastatin
Atorvastatin 10-20 mg for 18 months of treatment. Start dose is 10 mg, adjusted to 20 mg after 15-30 days if no sideeffects occurs.
干预措施: Atorvastatin 10mg (Drug)
Control
Placebo of atorvastatin 10 mg, 1-2 tablets for 18 months of treatment. Start dose is 1 tablet (10 mg placebo), adjusted to 2 tablets (20 mg placebo) after 15-30 days if no side effects occurs.
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Composite endpoint of numbers of death or liver transplantation
时间窗: 1.5 years
Number of hospitalizations with liver related complications
时间窗: 1.5 years
次要结局
- Number of Patients developing decompensation of liver cirrhosis(1.5 and 5 years)
- Number of adverse events(1.5 years (18 months))
- Inflammation and macrophage activation(0.5 and 1.5 years)
- Change in clinical score(0.5, 1.5 years)
- Numbers of episodes of decompensation(1.5 and 5 years)
- Change in clinical score Child-Turcotte-Pugh(0.5 and 1.5 years)
- Protein activity in the hepatic stellate cell(0.5 years)
- Cell activation(0.5 years)
- Time to first hospital admission due to decompensation or complications of liver cirrhosis(1.5 and 5 years)
- Patient survival(1.5 and 5 years)
- Composite endpoint of numbers of death or liver transplantation(5 years)
- Number of hospitalization with liver related complications(5 years)
- Change in clinical score, Frailty Index(0.5, 1.5 years)
研究者
Nina Kimer
MD, PhD, Clinician Researcher
Copenhagen University Hospital, Hvidovre