Pilot CMV Prevention Trial in Pediatric Lung Transplant

儿童肺移植 CMV 预防试点试验

• 批准号: 7271417
• 负责人: Lara A DANZIGER-ISAKOV
• 金额: $ 12.91万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7271417
• 关键词: Acute; Acyclovir; Adjuvant; Adult; Adverse effects; Adverse event; Antiviral Agents; Biochemical; Biometry; Bone Marrow; Bronchiolitis Obliterans; Caring; Cessation of life; Child; Childhood; Clinic; Clinical Investigator; Clinical Trials; Cohort Studies; Communicable Diseases; Confidence Intervals; Cytomegalovirus; Cytomegalovirus Infections; Data; Development; Development Plans; Disease; Drug Formulations; End Point; Epidemiology; Foundations; Frequencies; Ganciclovir; Globulins; Heart; Hepatic; Immunology; Immunosuppression; Infection; Infection prevention; Institution; Intervention; Intervention Trial; Intravenous; Kidney; Laboratories; Lung; Lung Transplantation; Lung diseases; Lymphoproliferative Disorders; Methods; Modeling; Monitor; Morbidity - disease rate; Mycoses; Neoadjuvant Therapy; Nephrotoxic; Neurologic; Numbers; Odds Ratio; Oral; Organ Transplantation; Patients; Personal Communication; Pharmaceutical Preparations; Physicians; Pilot Projects; Population; Predisposition; Preparation; Prevention; Principal Investigator; Program Development; Prophylactic treatment; Purpose; Randomized; Range; Rate; Reporting; Research Methodology; Risk; Risk Factors; Role; Safety; Scientist; Score; Sepsis; Severities; Site; Solid; Staging; Standards of Weights and Measures; Structure; Syndrome; Target Populations; Testing; Therapeutic immunosuppression; Time; Toxic effect; Training; Transplant Recipients; Transplantation; Treatment Protocols; Valganciclovir; Viral; Viremia; Week; base; career; clinical research site; experience; gastrointestinal; interest; liver transplantation; mortality; patient oriented research; pilot trial; prevent; programs; prophylactic; prospective; retransplantation; virology

The overall objectives of this proposal are to determine the epidemiology and best prevention regimens tor cytomegalovirus (CMV) infection for pediatric lung transplant recipients. In pediatric lung transplantation, CMV infection occurs in 23% of recipients and was associated with a four-fold increase in death or retransplantation in a single-center study. The optimal methods for prevention of CMV infection are uncertain. F'urther, the specific side effect profile of CMV prevention regimens has not been documented in this population. The data gained in pursuit of these studies will provide background information for the development of prospective clinical trials to answer the questions of how to best prevent infection related morbidity and mortality in pediatric lung transplant recipients. The following aims will be accomplished 1) extension of the single-center pilot trial initiated by the applicant to evaluate the feasibility, toxicity and short-term efficacy of prolonged intravenous ganciclovir; 2) assessment of valganciclovir (VGCV) side effects in adult lung transplant recipients; and 3) a multi-center study with subjects from at least 11 clinical sites. The pilot study aims to determine the feasibility, safety and short-term efficacy of prolonging ganciclovir prophylaxis from 6 weeks to 12 weeks in pediatric lung transplant recipients. The adult pilot study aims to assess the side effect profile of oral VGCV in adult lung transplant recipients. The multi-center study aims to evaluate the impact of CMV infection on death/retransplantation and other transplant-related morbidity in the first year after transplantation as well as to evaluate the impact of CMV hyperimmune globulin (CMVIG) on the rate of CMV infection. While accomplishing these aims, the applicant will have the opportunity to complete a structured 5-year career development program to develop into an independent clinical investigator. The objectives of the career development plan include 1) advanced training in research methods, epidemiology, biostatistics, virology and immunology, 2) use of patient-oriented research approach to confirm the impact of a modifiable infection in pediatric lung transplant recipients in the first year after pediatric lung transplantation and to determine the impact of various preventative regimens for CMV during the first year after pediatric lung transplantation, 3) using the results of the patient-oriented research to develop prospective intervention trials to decrease the morbidity and mortality associated with CMV in pediatric lung transplant recipients, and 4) development into a physician scientist in Pediatric Infectious Diseases performing independent patient-oriented research in a major academic center. Specific studies in pediatric lung transplant recipients evaluating the feasibility of prolonged prevention regimens, the impact of CMV infection and role of various prevention regimens are needed to reduce morbidity and mortality after pediatric lung transplantation. Estimating the side effects of VGCV in adult lung recipients will expedite the transition to oral agents in children. After completion, the applicant will have sufficient preliminary data to propose a multi-center prevention trial for CMV infection in pediatric lung transplant recipients.

该提案的总体目标是确定流行病学和最佳预防方案 儿童肺移植受者的巨细胞病毒（CMV）感染。在小儿肺移植中，CMV 23% 的受者发生感染，并且与死亡或再移植率增加四倍相关 单中心研究。预防 CMV 感染的最佳方法尚不确定。另外，具体方面 尚未记录 CMV 预防方案在该人群中的效果。追求中获得的数据 这些研究将为前瞻性临床试验的发展提供背景信息，以回答这个问题 如何最好地预防儿科肺移植受者感染相关的发病率和死亡率的问题。这 将实现以下目标 1）延长申请人发起的单中心试点试验的评估 长期静脉注射更昔洛韦的可行性、毒性和短期疗效； 2) 缬更昔洛韦的评估 (VGCV) 成人肺移植受者的副作用； 3) 一项多中心研究，受试者至少来自 11 个国家 临床场所。该试点研究旨在确定延长更昔洛韦疗程的可行性、安全性和短期疗效 小儿肺移植受者的预防时间为 6 周至 12 周。成人试点研究旨在评估 成人肺移植受者口服 VGCV 的副作用概况。这项多中心研究旨在评估 CMV 感染对术后第一年死亡/再移植和其他移植相关发病率的影响 移植以及评估 CMV 超免疫球蛋白 (CMVIG) 对 CMV 发生率的影响 感染。在实现这些目标的同时，申请人将有机会完成结构化的 5 年计划 发展成为独立临床研究者的职业发展计划。职业目标 发展计划包括1）研究方法、流行病学、生物统计学、病毒学和 免疫学，2) 使用以患者为导向的研究方法来确认可改变的感染对儿科的影响 肺移植受者在儿科肺移植后第一年的情况，并确定各种因素的影响 小儿肺移植后第一年的 CMV 预防方案，3) 使用 以患者为导向的研究，开展前瞻性干预试验，以降低发病率和死亡率 与儿科肺移植受者的 CMV 相关，以及 4) 发展成为儿科医师科学家 传染病在主要学术中心进行独立的以患者为导向的研究。具体研究 在儿科肺移植受者中评估延长预防方案的可行性、CMV 的影响 需要了解感染和各种预防方案的作用，以降低小儿肺结核后的发病率和死亡率 移植。评估 VGCV 对成年肺受体的副作用将加快向口服药物的过渡 在儿童中。完成后，申请人将有足够的初步数据来提出多中心预防方案 儿科肺移植受者 CMV 感染试验。