Pilot CMV Prevention Trial in Pediatric Lung Transplant

这项建议的总体目标是确定流行病学和最佳预防方案。 小儿肺移植受者巨细胞病毒感染的研究在儿童肺移植中，巨细胞病毒 感染发生在23%的受者身上，并与死亡或再次移植相关的四倍于 单中心研究。预防巨细胞病毒感染的最佳方法尚不确定。F‘urther，具体的一面 巨细胞病毒预防方案在该人群中的效果还没有记录在案。在追踪的过程中获得的数据 这些研究将为开发前瞻性临床试验提供背景信息，以回答 如何最好地预防儿童肺移植受者感染相关的发病率和死亡率的问题。这个 将实现以下目标：1)延长由申请人发起评估的单中心试点 更昔洛韦长期静脉滴注的可行性、毒性和短期疗效：2)万乃昔洛韦的评价 (VGCV)成人肺移植受者的副作用；以及3)一项多中心研究，受试者至少有11人 临床站点。这项初步研究旨在确定延长更昔洛韦的可行性、安全性和短期疗效 儿童肺移植受者的预防性治疗时间为6周至12周。这项成人试点研究旨在评估 口服vGCV在成人肺移植受者中的副作用概况。这项多中心研究旨在评估 巨细胞病毒感染对移植后第一年死亡/再移植和其他移植相关发病率的影响 并评价CMV高免疫球蛋白(CMVIG)对移植后CMV感染率的影响 感染。在实现这些目标的同时，申请者将有机会完成一个结构化的5年制课程。 职业发展计划，发展成为一名独立的临床研究员。职业生涯的目标 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)使用以患者为中心的研究方法来确认可改变的儿科感染的影响 肺移植受者在儿童肺移植后第一年及确定各种因素的影响 儿童肺移植后一年内巨细胞病毒的预防方案，3)使用 以患者为中心的研究，开发前瞻性干预试验，以降低发病率和死亡率 与儿童肺移植受者的巨细胞病毒相关，以及4)发展成为儿科的内科科学家 传染病在一个主要的学术中心进行以病人为中心的独立研究。具体研究 在评估延长预防方案的可行性的儿童肺移植受者中，巨细胞病毒的影响 减少小儿肺部感染和死亡率需要各种预防措施的作用 移植。评估vGCV对成人肺移植受者的副作用将加速向口服药物的过渡 在孩子们身上。完成后，申请人将有足够的初步数据提出多中心预防 儿童肺移植受者巨细胞病毒感染试验。

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.