PREVENTION OF ESOPHAGEAL VARICES BY B-ADRENERGIC BLOCKER

B-肾上腺素能阻滞剂预防食管静脉曲张

• 批准号: 3247981
• 负责人: ROBERTO J GROSZMANN
• 金额: $ 40.6万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1998-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3247981
• 关键词: ascites; beta antiadrenergic agent; clinical trials; disease /disorder prevention /control; esophageal varices; hepatic coma /encephalopathy; human mortality; human subject; human therapy evaluation; liver cirrhosis; liver disorder chemotherapy; liver transplantation; portal hypertension; propranolol

Cirrhosis is the fourth leading cause of death in the United States in individuals under the age of 65, the productive years of life. It affects men and women equally, and impacts on all races and socio- economical levels. Portal hypertension is the main complication of cirrhosis, regardless of etiology. Gastroesophageal varices and variceal hemorrhage are a direct consequence of portal hypertension and account in large part for the high mortality of cirrhosis. Varices result from porto-systemic collaterals that develop as portal pressure increases. Non-selective beta-adrenergic blockers decrease portal pressure and have been shown to prevent the first variceal hemorrhage in patients with cirrhosis and varices. However, a beneficial effect on survival has not been clearly demonstrated. This is probably related to the advanced stage of cirrhosis at the time beta- blocker therapy is initiated, since in these studies patients already have varices and frequently have ascites. Experimental studies have shown that propranolol therapy, administered in the early stages of portal hypertension, can prevent the development of porto-systemic collaterals. Early portal hypotensive therapy would be beneficial not only because it may prevent or delay the formation of varices (and consequently of variceal hemorrhage), but because it may prevent or delay the development of other complications of portal hypertension, such as ascites and porto-systemic encephalopathy. This trial is designed as a prospective, randomized, placebo-controlled, double-blind trial of 212 patients with cirrhosis and portal hypertension. Its primary aim is to investigate if early beta-adrenergic therapy can prevent or delay the development of gastroesophageal varices in patients with cirrhosis and portal hypertension. Secondary aims will examine whether this therapy prevents or delays other complications of portal hypertension such as ascites and porto-systemic encephalopathy, as well as liver transplantation or death. Patients with cirrhosis, without varices on endoscopy and with a portal pressure of greater than or equal to 6 mmHg will be included and will be followed for up to 5 years. In planning the trial, we assumed a rate of development of varices of 50% at 4 years. The calculated sample size of 2123 ensures high statistical power (80%) to detect a reduction in varices to 30% in the propranolol group. The trial is highly significant for the promise it holds for the treatment of cirrhosis of all etiologies and for an understanding of the natural history of the disease. The four centers involved are widely renown for their studies in this area and have collaborated productively in the past, including the only published double-blind trial of propranolol in the prevention of first variceal hemorrhage in patients with cirrhosis and varices.

肝硬化是美国第四大死亡原因 65岁以下的个人是生命的生产年份。 它 平等影响男人和女人，并对所有种族和社会的影响 经济水平。 门户高血压是 肝硬化，无论病因如何。 胃管静脉曲张和静脉曲张 出血是门户高血压和账目的直接结果 在很大程度上是肝硬化死亡率。 静脉曲张由 随着门户压力增加而发展的港口系统侧支。 非选择性β-肾上腺素能阻滞剂减少门户 压力并已被证明可以防止第一个静脉曲张 肝硬化和静脉曲张患者的出血。 但是， 对生存的有益影响尚未清楚地证明。 这 可能与当时的肝硬化的晚期阶段有关 启动阻滞剂治疗，因为在这些研究中已经患者 有静脉曲张，经常有腹水。 实验研究已有 表明普萘洛尔疗法在早期的早期阶段进行 门户高血压，可以防止港口系统的发展 抵押品。 早期的门户降压疗法将是有益的 仅仅因为它可能会阻止或延迟静脉曲张的形成（和 因此，静脉曲张出血），但因为它可能预防或延迟 门户高血压的其他并发症的发展，例如 腹水和港口系统脑病。 该试验被设计为一个前瞻性，随机，安慰剂对照， 212例肝硬化患者和门户的双盲试验 高血压。 它的主要目的是调查早期β-肾上腺素能是否 治疗可以预防或延迟胃食管反尼的发展 肝硬化和门静脉高血压患者。 次要目标将 检查该疗法是否预防或延迟其他并发症 门户高血压，例如腹水和港口系统性脑病， 以及肝移植或死亡。 肝硬化患者 没有静脉曲张的内窥镜检查，门户压力大于 或等于6 mmHg，将遵循最多5 年。 在计划试验时，我们假设 4年时的50％的静脉曲张。 计算的样本量为2123确保 高统计功率（80％），以检测静脉曲张的降低至30％ 普萘洛尔组。 审判对于承诺非常重要 它具有治疗所有病因的肝硬化和 了解该疾病的自然史。 四个中心 涉及在这一领域的研究中广为人知，并且 过去有效地合作，包括唯一出版的 普萘洛尔的双盲试验预防第一静脉曲张 肝硬化和静脉曲张患者的出血。