Randomized, Double-Blind Study of Timolol (A Nonselective Beta-Adrenergic Blocker) vs Placebo to Prevent Complications of Hepatic Portal Hypertension in Patients With Cirrhosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 213
- 试验地点
- 5
- 主要终点
- Varices
研究概览
简要总结
The purpose of this study is to learn whether timolol is useful in preventing or delaying the appearance of gastroesophageal varices, a complication that may develop in the future as a consequence of liver disease. Cirrhosis causes an increased resistance of blood flowing through the liver. This leads to an increased pressure in the portal vein (the vein that takes blood to your liver). High portal pressure is responsible for the appearance of complications of chronic liver disease such as varices and variceal bleeding (bleeding from veins in your esophagus). Timolol belongs to a group of medications called beta-blockers. Beta-blockers decrease high portal pressure and previous studies have shown that beta-blocker pills are useful in preventing bleeding from varices in patients who already have varices. A more desirable effect would be if these pills could prevent not only bleeding from varices but the appearance of varices (and therefore of bleeding).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Liver biopsy compatible with cirrhosis.
- •Absence of gastroesophageal varices.
- •An increased hepatic venous pressure gradient (HVPG) (6mmHg).
- •Age over 18 and below 76 years.
- •Informed, written consent.
- •Absence of exclusion criteria.
排除标准
- •Presence of ascites that requires specific treatment (diuretics, paracentesis, peritoneo-venous shunt, etc).
- •Proven hepatocellular carcinoma by radiological or histological criteria.
- •Splenic or portal vein thrombosis by Doppler-ultrasound.
- •Presence of any concurrent disease that is expected to decrease life expectancy to less than one year.
- •Patients taking diuretics, beta-blockers, clonidine, prazosin, nitrates, molsidomine and any drug which may have an effect on splanchnic hemodynamics/portal pressure.
- •Patients participating in other pharmacological randomized clinical trials.
- •Patients with primary biliary cirrhosis and primary sclerosing cholangitis will also be excluded since these entities have a slower progression of the disease, are usually enrolled in other clinical trials and are transplanted at an earlier stage.
- •Contraindications to beta-blockers: asthma, COPD with positive broncoconstrictive test, heart failure, A-V block, aortic valve stenosis, organic psychosis, insulin-dependent diabetes, hypersensitivity to beta-blockers.
- •Women who are pregnant, nursing or of childbearing potential and who are not using oral or mechanical contraception.
研究组 & 干预措施
Timolol Maleate
Dose titrated from 5 mg per day to up to 80 mg per day depending on heart rate
干预措施: Timolol Maleate (Drug)
Placebo
Timelol placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Varices
时间窗: 6 years
Development of varices
次要结局
未报告次要终点