ESOPHAGEAL VARICES BY B-ADRENERGIC BLOCKERS

B-肾上腺素能阻滞剂治疗食管静脉曲张

• 批准号: 2614182
• 负责人: ROBERTO J GROSZMANN
• 金额: $ 57.01万
• 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 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2614182
• 关键词: ascites; beta antiadrenergic agent; clinical trials; disease /disorder prevention /control; endoscopy; esophageal varices; hepatic coma /encephalopathy; human mortality; human subject; human therapy evaluation; liver cirrhosis; liver disorder chemotherapy; liver transplantation; placebos; portal hypertension; propranolol

Cirrhosis is the fifth 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. Non-selective beta- adrenergic blockers decrease portal pressure and have been shown to prevent the first variceal hemorrhage in patients with cirrhosis and varices. Early portal hypotensive therapy, before the patients develop varices, would be beneficial not only because it may prevent or delay the formation of varices (and variceal hemorrhage) but because it may prevent or delay the development of other complications of portal hypertension, such a ascites. This ongoing multi-center, prospective, randomized, placebo-controlled, double-blind trial was designed with the primary aim of investigating if early therapy with timolol, a non- selective beta-adrenergic blocker, can prevent or delay the development of varices in patients with cirrhosis and portal hypertension. Secondary aims will examine whether timolol 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 portal hypertension (portal pressure greater than 6 mmHg) are included in the study. This grant application was funded in April of 1993 and patient randomization began in August of 1993. Patient accrual took longer than originally estimated, however it is now certain that the number of 190 patients required for the study will have been randomized by the end of the current funding period (March 1998), since at the writing of this proposal 158 patients had already been randomized. In calculating sample size, we assumed a rate of development of varices of 50 percent at 4 years in the control arm, to be reduced to 30 percent in the timolol arm. So far our observed rates for development of varices are consistent with our planned estimates. However, we have now estimated that a minimum follow-up of 4 years (after last patient is recruited) is necessary to ensure high statistical power (80 percent at the 2-sided 0.05 level). 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.

肝硬化是美国第五大死亡原因， 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。 非选择性β- 肾上腺素能阻滞剂降低门静脉压力， 预防肝硬化患者的首次静脉曲张出血， 静脉曲张 早期门静脉扩张治疗，在患者发生 静脉曲张，将是有益的，不仅因为它可以防止或延迟 静脉曲张（和静脉曲张出血）的形成，但因为它可能 预防或延缓门脉其他并发症的发生 高血压，如腹水。这项正在进行的多中心，前瞻性， 随机、安慰剂对照、双盲试验设计， 主要目的是研究噻吗洛尔（一种 选择性β-肾上腺素能阻滞剂，可以预防或延迟发展 肝硬化和门静脉高压症患者静脉曲张的发生率。二次 aims将检查噻吗洛尔是否能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。 患者 肝硬化，内镜检查无静脉曲张， 高血压（门静脉压力大于6 mmHg）包括在 study. 这项拨款申请于1993年4月获得资助， 随机化开始于1993年8月。 患者累积时间超过 最初估计，但现在可以肯定的是， 研究所需的患者将在 目前的供资期间（1998年3月），因为在编写本报告时， 158名患者已被随机分组。 在计算 样本量，我们假设静脉曲张的发生率为50 在对照组的4年中， 到目前为止，我们观察到的静脉曲张发生率为 这与我们的预期相符。 然而，我们现在估计 至少随访4年（招募最后一例患者后） 是确保高统计功效（双侧80%）所必需的 0.05水平）。 这次审判对它所带来的希望意义重大 用于治疗所有病因的肝硬化， 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。