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: 6734371
• 负责人: ROBERTO J GROSZMANN
• 金额: $ 7.25万
• 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 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6734371
• 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。 非选择性β- 肾上腺素能阻滞剂降低了门户压力，并已证明 防止肝硬化患者的第一次静脉曲张出血 静脉曲张。 早期的门户降压疗法，在患者发展之前 静脉曲张，不仅是因为它可以防止或延迟 静脉曲张（和静脉曲张出血）的形成 防止或延迟门户其他并发症的发展 高血压，这样的腹水。这种持续的多中心，潜在的 随机，安慰剂对照，双盲试验设计了 研究是否早期治疗蒂莫洛（Timolol）的主要目的 选择性β-肾上腺素能阻断器，可以防止或延迟开发 肝硬化和门静脉高血压患者的静脉曲张。次要 目标会检查蒂莫洛是否阻止或延迟其他并发症 门户高血压，例如腹水和港口系统 脑病，以及肝移植或死亡。 患者 肝硬化，内窥镜检查没有静脉曲张和门户 高血压（门户压力大于6 mmHg）包括 学习。 该赠款申请于1993年4月和患者资助 随机分组始于1993年8月。患者的计费时间比 最初估计，但是现在可以肯定的是190 该研究所需的患者将在结束之前随机分组 当前的资金期（1998年3月），因为在撰写本文时 提案158例患者已经被随机分组​​。 在计算中 样本量，我们假设静脉曲张的发展速率为50％ 在控制臂的4年中，将减少到30％ 蒂莫洛臂。 到目前为止，我们观察到的静脉曲张发展速度是 与我们计划的估计一致。 但是，我们现在估计 最小随访4年（招募了最后一个患者） 对于确保高统计能力是必要的（2面的80％ 0.05级）。 审判对于其持有的承诺非常重要 用于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。

项目成果

The portal pressure response to beta-blockade is greater in cirrhotic patients without varices than in those with varices.

无静脉曲张的肝硬化患者对β受体阻滞剂的门静脉压力反应比有静脉曲张的患者更大。

• DOI: 10.1053/gast.1997.v112.pm9178694
• 发表时间: 1997
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Escorsell,A;Ferayorni,L;Bosch,J;García-Pagán,JC;García-Tsao,G;Grace,ND;Rodés,J;Groszmann,RJ
• 通讯作者: Groszmann,RJ

Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis.

• DOI: 10.1016/j.cgh.2009.02.021
• 发表时间: 2009-06
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 作者: Qamar AA;Grace ND;Groszmann RJ;Garcia-Tsao G;Bosch J;Burroughs AK;Ripoll C;Maurer R;Planas R;Escorsell A;Garcia-Pagan JC;Patch D;Matloff DS;Makuch R;Rendon G;Portal Hypertension Collaborative Group
• 通讯作者: Portal Hypertension Collaborative Group