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岁以下的人，生命的生产年数。 它 对男女的影响是平等的，对所有种族和社会都有影响， 经济水平。 门静脉高压症是肝硬化的主要并发症， 肝硬化，不论病因。 胃食管静脉曲张 出血是门静脉高压直接后果， 在很大程度上是因为肝硬化的高死亡率。 静脉曲张是由 随着门静脉压力增加而形成的门体侧支循环。 非选择性β-肾上腺素能受体阻滞剂减少门静脉 压力，并已被证明可以防止第一次静脉曲张 肝硬化和静脉曲张患者出血。 但 对生存的有益影响尚未得到明确证实。 这 很可能与肝硬化晚期有关 开始阻滞剂治疗，因为在这些研究中， 有静脉曲张，经常有腹水。 实验研究 表明在早期阶段给予普萘洛尔治疗， 门静脉高压症，可防止门体循环的发展 侧枝。 早期门静脉扩张治疗是有益的， 只是因为它可以防止或延迟静脉曲张的形成（和 但由于它可以防止或延迟 门静脉高压症的其他并发症的发展，如 腹水和门体脑病。 本试验设计为前瞻性、随机、安慰剂对照， 212例肝硬化门脉高压患者的双盲试验 高血压 其主要目的是研究早期β-肾上腺素能 治疗可以预防或延缓胃食管静脉曲张的发展 肝硬化和门静脉高压症患者。 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， 门静脉高压症如腹水和门体脑病， 以及肝移植或死亡。 肝硬化患者， 内镜检查无静脉曲张，门静脉压力大于 或等于6 mmHg，并将随访最多5 年 在计划试验时，我们假设 4年时静脉曲张50%。 计算的样本量为2123， 检测静脉曲张减少至30%的统计功效较高（80%）， 普萘洛尔组。 这次审判对于实现 它适用于所有病因的肝硬化的治疗， 了解疾病的自然史。 四个中心 参与者因其在这一领域的研究而闻名， 在过去的合作富有成效，包括唯一出版的 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出血。