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.

年，肝硬变是美国第四大死因 65岁以下的人，是人生的生产年限。它 对男性和女性的影响是平等的，对所有种族和社会- 经济水平。门静脉高压症是门静脉高压症的主要并发症 肝硬变，不分病因。胃食道静脉曲张和静脉曲张 出血是门静脉高压症的直接后果，并说明 这在很大程度上是因为肝硬变的高死亡率。精索静脉曲张由 门脉--随着门脉压力的增加而发展的系统性侧支。 非选择性β-肾上腺素能阻滞剂降低门脉 压力，并已被证明可以预防第一次静脉曲张 肝硬变和静脉曲张患者的出血。然而，a 对生存的有益影响还没有得到明确的证明。这 可能与贝塔时间的晚期肝硬化有关- 阻滞剂治疗开始了，因为在这些研究中，患者已经 有静脉曲张，经常有腹水。实验研究已经 显示心得安治疗，在早期给予心得安治疗 门静脉高压症，可预防门静脉全身性病变的发展 抵押品。早期门静脉降压治疗将是有益的 仅仅是因为它可以防止或延缓静脉曲张的形成(和 因此导致静脉曲张出血)，但因为它可以预防或延迟 门静脉高压症的其他并发症的发展，如 腹水和门脉全身性脑病。 这项试验设计为前瞻性、随机、安慰剂对照、 212例肝硬变门脉病变患者的双盲试验 高血压。其主要目的是研究早期的β-肾上腺素能 治疗可以预防或延缓胃食道静脉曲张的发展 在有肝硬变和门脉高压的患者中。次要目标将 检查这种疗法是否预防或延缓了其他并发症 门静脉高压症，如腹水和门脉系统性脑病， 以及肝移植或死亡。患有肝硬变的患者， 内窥镜检查无静脉曲张且门脉压力大于 或等于6毫米汞柱将包括在内，并将被跟踪最多5 好几年了。在计划试验时，我们假设开发速度为 术后4年静脉曲张发生率为50%。2123的计算样本量确保 高统计能力(80%)，检测静脉曲张减少到30% 普萘洛尔组。这场审判对这一承诺意义重大 它适用于各种原因的肝硬变的治疗和一种 了解该病的自然病史。四大中心 他们在这一领域的研究广为人知，并拥有 在过去进行了富有成效的合作，包括唯一出版的 普奈洛尔预防首次精索静脉曲张的双盲试验 肝硬变和静脉曲张患者的出血。