Angiotensin Receptor Blockade an Anti-Fibrotic Intervention in Patients With Chronic Hepatitis C
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Primary: • Stellate cell activity by alpha SMA stain quantitated by morphometry
研究概览
简要总结
Hepatitis C is the most common reason for liver transplantation in the United States and affects nearly 4 million Americans. Treatments for hepatitis C are available but are poorly tolerated and are not always effective. Morbidity and mortality from hepatitis C are related to the development and progression of hepatic fibrosis to cirrhosis and end stage liver disease. Efforts to block progression of liver disease would thus result in prevention of morbidity and mortality as well as costs incurred by the health system in the care of these conditions.
Scar tissue in the liver is secreted by a type of cell, called the stellate cell, in an activated state. This cell carries a receptor for angiotensin, a hormone, when activated. If this receptor is blocked, the cell becomes inactive and does not participate in scar tissue formation. Thus, we hypothesize that using a drug such as candesartan, which blocks angiotensin receptors, should result in less scar tissue formation in the livers of patients with hepatitis C.
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)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults, age 21 and older
- •Patients with viral hepatitis C that are not on interferon based therapy.
- •Detectable viral load
- •Baseline biopsy within six months or willing to undergo biopsy prior to drug initiation
- •At least grade 2 inflammation on biopsy, fibrosis of stage 1 or higher
- •Willing to undergo biopsy at the end of treatment
- •No interferon for at least 6 months prior to or after initial biopsy for study
排除标准
- •Renal impairment defined by a serum creatinine of >1.8
- •Congestive heart failure
- •Hepatocellular cancer
- •Concurrent treatment with pentoxyfylline, steroids, interferon alpha or interferon gamma.
- •Active psychosis (affective disorders without loss of reality testing acceptable)
- •Active IV drug use
- •Prior liver transplant
- •Pregnancy
- •Decompensated cirrhosis as defined by the presence of ascites, hepatic encephalopathy or coagulopathy with an INR>1.4
- •HIV seropositivity
- •Hypotension defined by a baseline systolic blood pressure of less than 90mm of mercury
- •Contraindication to ARB use or allergy to medication
- •Treatment with potassium sparing diuretics
研究组 & 干预措施
A
干预措施: Candesartan (Drug)
B
干预措施: Placebo (Drug)
结局指标
主要结局
Primary: • Stellate cell activity by alpha SMA stain quantitated by morphometry
时间窗: 48 weeks
• Hepatic fibrosis by morphometry
时间窗: 48 weeks
次要结局
- Surrogate markers for fibrosis (liver TGF-beta levels, serum procollagen-III peptide levels)(48 weeks)
- Functional status- Albumin, INR, T. Bilirubin, MELD score(48 weeks)