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）

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要肾脏移植可延长生命、提高生活质量并降低医疗费用。不幸的是，等待名单超过 94,000 人，而只有约 14,000 名死者捐献肾移植 (DDKT) 发生每年，许多患者等待 DDKT 的时间超过 5 年。对于老年人和其他一些患者群体来说，常见的等死。然而，来自感染丙型肝炎病毒 (HCV) 的捐献者的近 600 个肾脏被丢弃 2018 年（来自 HCV 病毒血症捐献者的肾脏总数的 50.1%）；数百个肾脏永远不会之所以采购，是因为人们认为没有中心会接受它们。试点临床试验的早期成功和来自 HCV 病毒血症供体的单中心系列肾移植已经证明了这种潜力实践将挽救生命的肾移植数量增加1000例以上年。然而，评估肾脏质量的主导系统也对任何肾脏质量应用较低的质量评分。来自 HCV 病毒血症供体的肾脏，从而促进器官废弃。此外，早期的经验没有良好匹配的比较组的非对照研究导致了意外并发症的报告和/或治疗失败率高于预期，这凸显了对正式多中心的需要临床试验。最近的报告强调了一系列移植后并发症，需要在大型多中心试验中进行评估，例如：a) 数名 HCV 阴性患者中的纤维化胆汁淤积性 HCV HCV 病毒血症供体的接受者； b) HCV 病毒血症受者 CMV 病毒血症发生率增加肾脏； c) 膜增生性肾小球肾炎。虽然这些并发症很少见，但它们强调移植领导者的观点，包括美国移植学会、美国移植协会肝病研究和美国传染病学会认为这种做法 “实验性”，最好在 IRB 批准的协议下进行，并获得严格的知情同意和获得 HCV 治疗的保证。此外，尽管 HCV 肾移植有所增加，将病毒血症供体转入 HCV 阴性患者，仍然存在需要解决的持续知识差距从患者、提供者和付款人的角度来看，这种做法被接受为常规临床护理。这项多中心试验旨在通过解决这些具体问题来弥补仍然存在的重大知识差距目标：a) 以狭窄的置信度估计 HCV 病毒血症肾脏的 HCV 阴性受者的 HCV 治愈率间隔; b) 确定同意接受 HCV 病毒血症肾脏是否可以提高生存率； c) 评估 1- 与匹配的对照者相比，HCV 病毒血症肾脏的肾功能年数； d) 评估HCV是否- HCV 病毒血症肾脏阴性受者感染 CMV 的风险增加； e) 确定是否 HCV 病毒血症与 HCV 阴性肾捐献者的慢性肾病病理学患病率相似。这首要目标是确定 HCV 病毒血症供体的肾脏是否可以安全地移植到 HCV 病毒血症患者体内。阴性终末期肾病患者。