A trial of transplanting Hepatitis C-viremic kidneys into Hepatitis C-Negative kidney recipients (THINKER-NEXT)

将丙型肝炎病毒血症肾脏移植到丙型肝炎阴性肾脏接受者的试验（THINKER-NEXT）

• 批准号: 10392517
• 负责人: David Seth Goldberg
• 金额: $ 149.33万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10392517
• 关键词: Acute Hepatitis C; Address; Allografting; American; Americas; Antiviral Agents; Antiviral Therapy; Benefits and Risks; Biopsy; Blinded; Cholestasis; Chronic Disease; Chronic Kidney Failure; Clinical Trials; Communicable Diseases; Confidence Intervals; Consent; Cytomegalovirus; Cytomegalovirus Infections; Data; Elderly; End stage renal failure; Ethicists; Evaluation; Fibrosis; Glomerular Filtration Rate; Glomerulonephritis; Goals; Health Care Costs; Hepatitis C; Hepatitis C Therapy; Hepatitis C Transmission; Hepatitis C virus; High Prevalence; Incidence; Inferior; Informed Consent; Injury; Institutional Review Boards; Insurance Carriers; Kidney; Kidney Transplantation; Knowledge; Life; Liver diseases; Mediating; Membranoproliferative Glomerulonephritis; Monitor; Multi-Institutional Clinical Trial; Multicenter Trials; Organ; Outcome; Overdose; Pathologic; Pathologist; Pathology; Patients; Perception; Persons; Pharmaceutical Preparations; Phenotype; Prevalence; Prospective Studies; Protocols documentation; Provider; Quality of life; Renal function; Reporting; Risk; Safety; Series; Societies; Specimen; Standardization; System; Testing; Transplant Recipients; Transplantation; Treatment Failure; Uncontrolled Study; Vascular Diseases; Viral; Viremia; Virus; Virus Diseases; Waiting Lists; Work; clinical care; cohort; comparison group; early experience; glomerulosclerosis; graft failure; implantation; improved; interstitial; kidney allograft; kidney biopsy; off-label use; opioid epidemic; post-transplant; side effect; standard of care; success; transplant centers

Project Summary/Abstract Kidney transplant extends life, improves quality of life, and reduces healthcare costs. Unfortunately, the waiting list exceeds 94,000 people while only approximately 14,000 deceased donor kidney transplants (DDKT) occur annually and many patients wait >5 years for a DDKT. For the elderly and some other patient groups, it is common to die waiting. Yet, nearly 600 kidneys from donors infected hepatitis C virus (HCV) were discarded in 2018 (50.1% of the total number of kidneys from HCV-viremic donors); hundreds more kidneys are never procured because of the perception that no center will accept them. Early successes of pilot clinical trials and single-center series of transplanting kidneys from HCV-viremic donors have demonstrated the potential for this practice to increase the number of lifesaving kidney transplants by more than 1,000 kidney transplants each year. However, the dominant system for assessing kidney quality also applies a lower quality score to any kidney from an HCV-viremic donor, thereby promoting organ discard. Also, early experiences from uncontrolled studies without well-matched comparator groups has led to reports of unexpected complications and/or higher than anticipated rates of treatment failures that underscore the need for a formal multi-center clinical trial. Recent reports have highlighted a series of post-transplant complications that necessitate evaluation in a large multi-center trial, for example: a) fibrosing cholestatic HCV in several HCV-negative recipients of an HCV-viremic donor; b) increased incidence of CMV viremia in recipients of HCV-viremic kidneys; and c) membranoproliferative glomerulonephritis. While these complications are rare, they underscore the view from transplant leaders, including the American Society of Transplantation, the American Association for the Study of Liver Diseases, and the Infectious Disease Society of America that this practice is considered `experimental' and is best performed under IRB-approved protocols with rigorous informed consent and assurances of access to HCV treatment. Furthermore, despite increased transplantation of kidneys from HCV- viremic donors into HCV-negative patients, there remain persistent knowledge gaps that need to be addressed for this practice to be accepted as routine clinical care from the perspective of patients, providers, and payers. This multi-center trial seeks to provide significant knowledge gaps that remain by addressing these specific aims: a) estimate HCV cure rates in HCV-negative recipients of HCV-viremic kidneys with a narrow confidence interval; b) determine whether consenting to receiving an HCV-viremic kidney improves survival; c) evaluate 1- year renal function of HCV-viremic kidneys compared to matched comparators; d) assess whether HCV- negative recipients of HCV-viremic kidneys have increased risks of CMV infection; and e) determine if the prevalence of chronic kidney disease pathology is similar in HCV-viremic vs HCV-negative kidney donors. The overarching goal is to determine if kidneys from HCV-viremic donors can safely be transplanted into HCV- negative patients with end-stage renal disease.

项目摘要/摘要 肾移植延长了生命，提高了生活质量，并降低了医疗成本。不幸的是，等待 名单上有超过94,000人，而只有大约14,000人进行了已故捐赠者肾脏移植(DDKT) 每年，许多患者都要等上5年才能接受DDKT治疗。对于老年人和其他一些患者群体来说，它是 在等待中死去是很常见的。然而，近600个来自感染丙型肝炎病毒(丙型肝炎病毒)的捐赠者的肾脏被丢弃在 2018年(占丙型肝炎病毒捐献者肾脏总数的50.1%)；另外数百个肾脏永远不会 采购是因为人们认为没有中心会接受他们。试点临床试验的早期成功和 来自丙型肝炎病毒携带者的单中心系列肾脏移植已经证明了这一潜力。 救命肾移植增加1,000余例的实践 年。然而，评估肾脏质量的主要系统也适用于较低的质量分数 来自丙型肝炎病毒携带者的肾脏，从而促进器官丢弃。此外，早期的经验来自 没有良好匹配的比较组的未对照研究导致了意外并发症的报告 和/或比预期更高的治疗失败率，这强调了正式的多中心的必要性 临床试验。最近的报道强调了移植后的一系列并发症，这些并发症使 一项大型多中心试验的评估，例如：a)几个丙型肝炎病毒阴性患者的胆汁淤积性丙型肝炎纤维化 丙型肝炎病毒携带者的受者；b)丙型肝炎病毒携带者受者巨细胞病毒血症发生率增加 C)膜增生性肾小球肾炎。虽然这些并发症很少见，但它们强调了 来自移植领袖的观点，包括美国移植学会、美国协会 对于肝病的研究，美国传染病学会认为这种做法 根据IRB批准的协议，最好在获得严格知情同意的情况下执行 获得丙型肝炎病毒治疗的保证。此外，尽管来自丙型肝炎病毒的肾脏移植增加了- 在向丙型肝炎病毒阴性患者注入病毒供体的情况下，仍然存在着需要解决的长期知识差距 从患者、提供者和付款人的角度来看，这种做法被接受为常规的临床护理。 这项多中心试验旨在通过解决以下具体问题来提供仍然存在的重大知识差距 目的：a)以狭隘的置信度估计丙型肝炎病毒感染肾的丙型肝炎病毒阴性受者的丙型肝炎病毒治愈率 间隔；b)确定同意接受丙型肝炎病毒肾是否可以提高存活率；c)评估1- 年丙型肝炎病毒携带者肾脏的肾功能与匹配的对照组比较；d)评估丙型肝炎病毒是否- 接受丙型肝炎病毒感染的肾脏阴性者巨细胞病毒感染的风险增加；以及e)确定 在丙型肝炎病毒携带者和丙型肝炎病毒阴性肾捐献者中，慢性肾脏疾病病理的患病率相似。这个 首要目标是确定来自丙型肝炎病毒携带者的肾脏是否可以安全地移植到丙型肝炎病毒中。 终末期肾病阴性患者。