Prevention of Progression of Portal Hypertension in Compensated Cirrhosis Using Selective Hepatic Vasodilators. A Double-blind, Multicenter,Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension
研究概览
简要总结
The purpose of this study is to determine whether simvastatin is effective in the prevention of progression of porta hypertension in compensated cirrhosis patients.
详细描述
Decompensation of cirrhosis is associated with a dramatic reduction of survival. Progression of portal hypertension (PHT) is the main determinant of decompensation that appears when portal pressure gradient (PPG) is ≥10mmHg (clinically significant HTP). 40% of compensated cirrhotic patients have mild PHT. However, with progression of disease 41% develop clinically significant PHT. In cirrhosis, PHT results from increased resistance to blood flow, with a dynamic component due to decreased nitric oxide (NO) bioavailability. In advanced disease increased portal venous inflow also contributes to PHT. Beta-blockers have not been useful in compensated cirrhosis with mild PHT. In early cirrhosis, vasodilators may be more adequate. Statins, drugs that inhibit the activity of HMG-CoA reductase, induce selective hepatic vasodilation due to an enhanced bioavailability of NO. Acutely, they decreases hepatic resistance, while with long-term use statins decreases PPG without deleterious effects on systemic circulation. This multicenter, randomized, double-blind placebo-controlled study is aimed at assessing whether treatment with simvastatin may prevent progression of mild PHT (with PPG between 6 and 10 mmHg) to clinically significant PHT. Patients with compensated cirrhosis, without previous decompensation, without esophageal varices at risk and with PPG between 6 and 10 mmHg will be included. The calculated sample size is 80 patients and the duration of the study 4 years (2 years including and a follow-up of at least 2 year).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Liver cirrhosis diagnosed by previous biopsy or by clinical, laboratory, ultrasound
- •Portal hypertension gradient between6 mmHg and10 mmHg
- •Absence of esophageal and gastric varices or small esophageal varices without red signs
- •Absence previous episodes of gastrointestinal hemorrhage, ascites, encephalopathy or jaundice
- •Written informed consent
排除标准
- •Age <18 and> 80 years,
- •Presence or history of ascites, clinical or ultrasound,
- •Previous decompensation of liver cirrhosis, ascites or SBP, bleeding varices, large varices, hepatic encephalopathy, jaundice,
- •Thrombosis splenoportal,
- •Hepatocellular carcinoma;
- •Child-Pugh >7 point
- •Any comorbidity that leads to a restriction therapy and / or a life expectancy <12 months
- •Absolute contraindication to treatment with statins or allergy Simvastatin;
- •Concomitant potent CYP3A4 inhibitors (eg., itraconazole, ketoconazole, protease inhibitors, HIV, erythromycin, clarithromycin, telithromycin and nefazodone),
- •Pretreatment (<1 month) with simvastatin or other lipid-lowering,
- •Previous episodes of rhabdomyolysis,
- •Active alcoholic hepatitis,
- •Refusal to participate in the study or the informed consent claim;
- •Pre-treatment with beta blockers or nitrates, or endoscopic treatment for varicose veins or portosystemic derivations;
- •Pregnancy and lactation.
研究组 & 干预措施
simvastatin
The experimental group will take simvastatin 40mg for at least two years.
干预措施: Simvastatin (Drug)
placebo
the control group wiil take placebo pills for at least two years.
干预措施: placebo (Drug)
结局指标
主要结局
the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension
时间窗: 4 years
The main objective is to assess whether, in patients with compensated cirrhosis and mild portal hypertension (GPP between 6 and 10mmHg), the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension and prevent the development of clinically significant HTP (defined GPP by a ≥ 10 mmHg)
次要结局
- Portal hypertension complications(four years)
- Adverse effects(four years)