PLANNING A CLINICAL TRIAL TO PREVENT POSTTRANSPLANT ALD

规划预防移植后酒精性肝病 (ALD) 的临床试验

• 批准号: 2766664
• 负责人: THOMAS P BERESFORD
• 金额: $ 6.3万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2766664
• 关键词: alcoholic hepatitis; alcoholic liver cirrhosis; alcoholism /alcohol abuse; alcoholism /alcohol abuse therapy; behavioral /social science research tag; clinical research; clinical trials; ethanol; health care service planning; health services research tag; homologous transplantation; human subject; liver transplantation; longitudinal human study; mental health services; psychopharmacology

Hepatic transplant for persons suffering from alcohol dependence (AD) remains controversial medical issue. Despite three year data collected by the present PI and associates showing uniquely high abstinent rates in this highly selected population, any alcohol use post-transplant reaches as high as 35-40 percent. While rates of alcohol related mortality post-transplant, such as that from Alcoholic Liver Disease (ALD), remain low at about 1-5 percent, any mortality due to a preventable return to ethanol ingestion in an AD group is medically unacceptable and a threat to providing liver transplant for ALD. The outcome figures cited above suggest two phenomena: 1) the limit of AD patient selection in assuring long term abstinence, and 2) the need for specific treatment of this unique population whose natural abstinence rate far exceeds those found in non-transplant AD cases. Further, longitudinal data suggest 3) that alcohol related mortality occurs after the first year post-transplant, so called late deaths. A clear need exists to design and implement effective treatment for this unique clinical population that takes into account their already high abstinent rate and their course of increasing risk for alcoholic relapse and late death due to recurrent ALD or other AD related injury. The consortium of liver transplant centers proposes to design and propose a randomized clinical trial of focused, active, long-term follow-up care in a test group of 205 AD liver transplant recipients versus standard care given to a control group of 205 AD liver graft recipients; ethanol use will be the primary outcome variable. This study, conducted in seven Centers, would be executed over five years with a goal of at least seven years treatment exposure. While intent, good will, and patient flow are in place, the consortium Centers unanimously believe that proper organization is not in place and must be developed. Therefore, the group of Centers supports the present proposal for a planning grant that would establish the structures, communications, methods, policies and procedures for the successful completion of a clinical trial specifically designed for AD liver transplant recipients. The present proposal seeks to create among the Centers 1) an organizational structure, 2) a shared theoretical framework, 3) mutually agreed upon treatment and control protocols 4) detailed logistical planning for the protocols, 5) reliable measures of ethanol use, 6) effective communications, data transfer and analysis capabilities and 7) an external review panel of experts. On completion of these tasks, the PI and consortium members expect to have in place not only a well constructed proposal but a demonstrably active, well functioning clinical research consortium capable of executing the proposed clinical trial.

酒精依赖者的肝移植 仍然是有争议的医疗问题。尽管收集了三年的数据 由目前的PI和同伙显示出独特的高禁欲率 在这个高度挑选的人群中，任何在移植后使用酒精的人 高达35%-40%。而酒精率与 移植后死亡率，如酒精性肝病 (ALD)，保持在约1%-5%的低水平，任何因 AD组可预防的酒精摄取从医学上讲是可以预防的 这是不可接受的，也是对ALD提供肝脏移植的威胁。这个 上面引用的结果数据表明了两个现象：1)AD的限度 在确保长期戒酒方面的患者选择，以及2)需要 对这一独特的自然禁欲人群的特殊待遇 这一比例远远超过非移植AD病例。此外， 纵向数据表明，与酒精有关的死亡会发生 移植后第一年，即所谓的晚期死亡。一目了然 需要设计和实施有效的治疗方法来治疗这种独特的 考虑到他们已经很高的禁欲的临床人口 酗酒复发和晚期酗酒风险增加的比率和过程 因ALD复发或其他AD相关损伤而死亡。 肝脏移植中心联盟建议设计和 提出一项集中、积极、长期的随机临床试验 205例AD肝移植受者的随访护理 对比给予205例AD肝移植的对照组的标准护理 接受者；乙醇的使用将是主要的结果变量。这 这项研究在七个中心进行，将在五年内完成 目标是至少七年的治疗暴露。在意图的同时， 善意和耐心流已经到位，财团中心 一致认为适当的组织没有到位，必须 被开发出来。 因此，该中心集团支持目前的提案，即 规划拨款，将建立结构，通信， 成功地完成一项 专为AD肝移植受者设计的临床试验。 本提案寻求在各中心之间创建1)一个 组织结构，2)共享的理论框架，3)相互 商定治疗和控制方案4)详细的后勤 规划方案，5)可靠的乙醇使用措施，6) 有效的通信、数据传输和分析能力以及 7)由专家组成的外部审查小组。在完成这些任务后， PI和财团成员希望不仅有一口井 构思的提案，但显然是积极的，运作良好的 有能力执行拟议临床研究的临床研究联合体 审判。