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: 2145812
• 负责人: ROBERTO J GROSZMANN
• 金额: $ 41.36万
• 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: 1993-04-20 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2145812
• 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，即生命的生产力年龄。 它 平等地影响男性和女性，并影响所有种族和社会 经济水平。 门静脉高压症是其主要并发症 肝硬化，无论病因如何。 胃食管静脉曲张和静脉曲张 出血是门静脉高压症的直接后果 很大程度上是因为肝硬化的高死亡率。 静脉曲张源于 随着门静脉压力增加而形成的门体循环。 非选择性β-肾上腺素能阻滞剂减少门脉 压力并已被证明可以预防第一次静脉曲张 肝硬化和静脉曲张患者的出血。 然而，一个 对生存的有益影响尚未得到明确证明。 这 可能与当时的肝硬化晚期有关 开始阻滞剂治疗，因为在这些研究中，患者已经 有静脉曲张并且经常有腹水。 实验研究有 研究表明，在早期阶段进行普萘洛尔治疗 门脉高压症，可预防门体系统疾病的发展 抵押品。 早期门脉低血压治疗是有益的 只是因为它可以预防或延缓静脉曲张的形成（并且 静脉曲张出血的结果），但因为它可以预防或延迟 门静脉高压症其他并发症的发展，例如 腹水和门体脑病。 该试验被设计为一项前瞻性、随机、安慰剂对照、 212 名肝硬化门脉患者的双盲试验 高血压。 其主要目的是研究早期β-肾上腺素能是否 治疗可以预防或延缓胃食管静脉曲张的发展 肝硬化和门脉高压患者。 次要目标将 检查这种疗法是否可以预防或延迟其他并发症 门脉高压，如腹水和门体性脑病， 以及肝移植或死亡。 肝硬化患者， 内窥镜检查无静脉曲张且门静脉压力大于 或等于 6 mmHg 将被包括在内，并将被跟踪最多 5 年。 在计划试验时，我们假设开发速度为 4 年时静脉曲张发生率为 50%。 计算出的样本量为 2123，确保 高统计功效 (80%) 可检测静脉曲张减少至 30% 普萘洛尔组。 此次审判对承诺意义重大 它适用于所有病因的肝硬化的治疗和 了解疾病的自然史。 四个中心 所涉及的人员在该领域的研究中享有盛誉，并且 过去曾进行过富有成效的合作，包括唯一发表的 普萘洛尔预防首次静脉曲张的双盲试验 肝硬化和静脉曲张患者的出血。