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.

年，肝硬变是美国第五大死因 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。非选择性测试版- 肾上腺素能阻滞剂可降低门脉压力，并已被证明 预防肝硬变患者首次静脉曲张破裂出血 静脉曲张。早期门静脉降压治疗，在患者病情发展之前 静脉曲张，是有益的，不仅因为它可以防止或延迟 静脉曲张的形成(和静脉曲张出血)，但因为它可能 预防或延缓门脉其他并发症的发展 高血压，这样的腹水。这个正在进行的多中心、前瞻性、 随机、安慰剂对照、双盲试验设计为 主要目的是研究是否早期使用噻吗洛尔治疗，一种非 选择性β-肾上腺素能阻滞剂，可防止或延缓疾病的发展 肝硬变和门脉高压症患者的静脉曲张。次要的 AIMS将检查噻吗洛尔是否可以预防或延迟其他并发症 门静脉高压症，如腹水和门体静脉高压 脑病，以及肝移植或死亡。病人 有肝硬变，内窥镜检查无静脉曲张，有门脉 高血压(门脉压力大于6毫米汞柱)包括在 学习。这项拨款申请是在1993年4月资助的，患者 随机化于1993年8月开始。患者收益花费的时间比 最初估计，但现在可以肯定的是，190人的数量 这项研究所需的患者将在#年末被随机分组。 本供资期间(1998年3月)，因为在撰写本文件时 建议158名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育率为50% 在控制臂工作4年，减少到30% 硫吗心安手臂。到目前为止，我们观察到的静脉曲张发育率是 与我们的计划估计一致。然而，我们现在已经估计 至少随访4年(最后一位患者入选后) 是确保高统计能力所必需的(80%在双面 0.05水平)。这场审判具有非常重要的意义，因为它所拥有的承诺 治疗各种原因的肝硬变 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。