To Study the Safety and Efficacy of Simvastatin in Patients With Hepatopulmonary Syndrome in Cirrhosis- A Double Blind Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Achievement of complete response by the end of 6 months
研究概览
简要总结
Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of end-stage liver disease that is characterized by decreased arterial oxygenation caused by intrapulmonary vascular dilatation. Due to the different diagnostic criteria used in different studies, its prevalence ranges from 4% to 47% in patients with cirrhosis. Main underlaying pathogensis for HPS being activation of macrophages which are responsible for iNOS, PDGF and VEGF release contributing to development of intrapulmonary vascular dilatation(IPVD) , and neoangiogenesis leading to anatomical shunt resulting decreased oxygenation. Sphingosine 1 phosphate (S1P) is an essential compound produced and secreted by endothelial cells, platelets and RBC's. S1P prevents adhesion, transmigration and release of inflammatory mediators from macrophages. S1P levels are decreased in cirrhotics. Simvastatin, a HMG CoA inhibitor has many pleotropic effects, Of which one is by agonizing the S1P response and improving oxygenation in HPS patients. Simvastatin at a optimal dose of 40mg/day for 6months. Pre and post simvastatin treatment related oxygenation changes and concurrently its effect on liver fibrosis will be evaluated.
详细描述
Methodology:
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Study population:All the consecutive patients of cirrhosis admitted to Hepatology department of ILBS will be evaluated for inclusion.
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Study design: Double Blind randomized control trial: Superiority trial. The study will be conductedin Department of Hepatology ILBS.
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Study period: 2 years
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Sample size:
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Assuming 40% as the response rate to simvastatin and 1% to standard medical treatment with α 5% , power 80% and superiority marging as 10% ,we need to enroll 36 cases 18 in each arm.Further considering 10% drop rate, decided to enroll 40 cases with 20 randomised to 2 groups using block randomisation method taking block score of 4.It is decided to allocate the cases in 2:1 ratio (Simvastatin 2: 1 Placebo) decided to enroll 45 cases so that 30 in simvastatin arm and 15 in standard medical therapy
(Not on pentoxiphylline) arm with block size 15
- Intervention:
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed case of Hepato-pulmonary syndrome AaPO2 > 15 mm Hg on standing room air arterial blood gas (ABG). PaO2<80 mmHg for clinical HPS between 18-70 years of years
- •Child A/B cirrhosis, Child C with CTP score of =/<10
- •Patient with no liver transplant option
排除标准
- •Child-C cirrhosis CTP >10
- •Very Severe HPS
- •Acute-on-chronic liver failure
- •Thrombosis of splenoportal axis
- •Hepatocellular carcinoma
- •Renal dysfunction
- •Patients intolerant to beta blockers (history of hypotension or bradycardia)
- •Contraindication for beta-blockers (history of chronic obstructive pulmonary disease, atrioventricular block)
- •Pregnant females
- •Refusal to participate in the study
- •Hepatic Hydrothorax
研究组 & 干预措施
Simvastatin with Standard Medical Treatment
Simvastatin 40mg OD plus standard treatment plus standard treatment (excluding Pentoxiphylline)
干预措施: Simvastatin 40mg (Drug)
Simvastatin with Standard Medical Treatment
Simvastatin 40mg OD plus standard treatment plus standard treatment (excluding Pentoxiphylline)
干预措施: Standard medical Treatment (Other)
Placebo with Standard Medical Treatment
Matched placebo plus standard treatment (excluding Pentoxiphylline)
干预措施: Placebo (Other)
Placebo with Standard Medical Treatment
Matched placebo plus standard treatment (excluding Pentoxiphylline)
干预措施: Standard medical Treatment (Other)
结局指标
主要结局
Achievement of complete response by the end of 6 months
时间窗: 6 months
次要结局
- Severity of Liver Disease(6 months)
- Development of serious adverse effects leading to withdrawal of the drug or death from any cause.(2 years)
- Transplant free survival(6 months)