Pilot CMV Prevention Trial in Pediatric Lung Transplant

儿童肺移植 CMV 预防试点试验

• 批准号: 7658943
• 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 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7658943
• 关键词: Acute; Acyclovir; Adjuvant; Adult; Adverse effects; Adverse event; Antiviral Agents; Biochemical; Biometry; Bone Marrow; Bronchiolitis Obliterans; 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; Epidemiologic Methods; 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; Odds Ratio; Oral; Organ Transplantation; Patients; Personal Communication; Pharmaceutical Preparations; Physicians; Pilot Projects; Population; Predisposition; Preparation; Prevention; Principal Investigator; Prophylactic treatment; Randomized; Reporting; Research Methodology; Risk; Risk Factors; Role; Safety; Scientist; Sepsis; Severities; Site; Solid; Staging; Structure; Syndrome; Target Populations; Testing; Time; Toxic effect; Training; Transplant Recipients; Transplantation; Treatment Protocols; Valganciclovir; Viral; Viremia; base; career development; clinical research site; experience; gastrointestinal; high risk; interest; liver transplantation; mortality; patient oriented research; pilot trial; prevent; programs; prophylactic; prospective; retransplantation; standard care; 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.

这项建议的总体目标是确定流行病学和最佳预防方案， 小儿肺移植受者的巨细胞病毒（CMV）感染。在小儿肺移植中，CMV 感染发生在23%的受者中，并且与死亡或再次移植的四倍增加相关。 单中心研究。预防CMV感染的最佳方法尚不确定。第二，具体方面 CMV预防方案在该人群中的效果特征尚未记录。在追求中获得的数据 这些研究将为前瞻性临床试验的发展提供背景信息， 如何最好地预防小儿肺移植受者感染相关的发病率和死亡率的问题。的 将实现以下目标：1）扩展申请人发起的单中心初步试验，以评估 长期静脉注射更昔洛韦的可行性、毒性和近期疗效; 2）评价缬更昔洛韦 （VGCV）在成人肺移植受者中的副作用;和3）多中心研究，受试者来自至少11个 临床现场。该试点研究旨在确定延长更昔洛韦的可行性、安全性和短期疗效 在儿科肺移植受者中预防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的副作用特征。多中心研究旨在评估 CMV感染对移植后第一年死亡/再次移植和其他移植相关发病率的影响 目的：观察巨细胞病毒（CMV）超免疫球蛋白（CMVIG）对CMV感染率的影响， 感染在实现这些目标的同时，申请人将有机会完成一个结构化的5年 职业发展计划，以发展成为一个独立的临床研究者。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，以确认儿科可改变感染的影响 儿童肺移植后第一年的肺移植受者，并确定各种 小儿肺移植后第一年CMV的预防方案，3）使用 以患者为导向的研究，开发前瞻性干预试验，以降低发病率和死亡率 与小儿肺移植受者中的CMV相关，以及4）发展成为儿科医生科学家 传染病在一个主要的学术中心进行独立的以病人为导向的研究。具体研究 在儿科肺移植受者中，评估长期预防方案的可行性， 感染和各种预防方案的作用，以减少发病率和死亡率后，小儿肺 移植评估VGCV在成人肺受体中的副作用将加速向口服药物的过渡 小儿完成后，申请人将有足够的初步数据，提出多中心预防 小儿肺移植受者巨细胞病毒感染的临床试验

项目成果

Long-term impact of respiratory viral infection after pediatric lung transplantation.

• DOI: 10.1111/j.1399-3046.2010.01296.x
• 发表时间: 2010-05
• 期刊: Pediatric transplantation
• 影响因子: 1.3
• 作者: Liu M;Mallory GB;Schecter MG;Worley S;Arrigain S;Robertson J;Elidemir O;Danziger-Isakov LA
• 通讯作者: Danziger-Isakov LA

Cytomegalovirus immunoglobulin decreases the risk of cytomegalovirus infection but not disease after pediatric lung transplantation.

巨细胞病毒免疫球蛋白可降低巨细胞病毒感染的风险，但不能降低小儿肺移植后疾病的风险。

• DOI: 10.1016/j.healun.2009.04.032
• 发表时间: 2009
• 期刊: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
• 作者: Ranganathan,Kavitha;Worley,Sarah;Michaels,MarianG;Arrigan,Susana;Aurora,Paul;Ballmann,Manfred;Boyer,Debra;Conrad,Carol;Eichler,Irmgard;Elidemir,Okan;Goldfarb,Samuel;MalloryJr,GeorgeB;Mogayzel,PeterJ;Parakininkas,Daiva;Solom
• 通讯作者: Solom

Fungal infections in pediatric lung transplant recipients: colonization and invasive disease.

儿科肺移植受者的真菌感染：定植和侵袭性疾病。

• DOI: 10.1016/j.healun.2009.06.006
• 发表时间: 2009
• 期刊: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
• 作者: Liu,Michael;Worley,Sarah;MalloryJr,GeorgeB;Arrigain,Sarah;Robertson,John;Schecter,MarcG;Elidemir,Okan;Danziger-Isakov,LaraA
• 通讯作者: Danziger-Isakov,LaraA

Tissue and species differences in bile salt-dependent neutral cholesteryl ester hydrolase activity and gene expression.

• DOI: 10.1161/01.atv.12.3.295
• 发表时间: 1992-03
• 期刊: Arteriosclerosis and thrombosis : a journal of vascular biology
• 作者: R. Zolfaghari;E. Harrison;J. Han;W. Rutter;E. Fisher

Minimal acute rejection in pediatric lung transplantation--does it matter?

小儿肺移植中的急性排斥反应最小——这重要吗？

• DOI: 10.1111/j.1399-3046.2009.01268.x
• 发表时间: 2010
• 期刊: Pediatric transplantation
• 影响因子: 1.3
• 作者: Benden,Christian;Faro,Albert;Worley,Sarah;Arrigain,Susana;Aurora,Paul;Ballmann,Manfred;Boyer,Debra;Conrad,Carol;Eichler,Irmgard;Elidemir,Okan;Goldfarb,Samuel;Mallory,GeorgeB;Mogayzel,PeterJ;Parakininkas,Daiva;Solomon,Melinda
• 通讯作者: Solomon,Melinda