PEGYLATED INTERFERON +/- RIBAVIRIN FOR CHILDREN WITH HCV (PEDS-C)

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 美国约有15万名婴儿、儿童和青少年患有慢性丙型肝炎病毒（CHC）感染。 α-干扰素（IFN）单独或与利巴韦林和聚乙二醇化干扰素（PEG）与RV组合已被FDA批准用于18岁以上的受试者。 Rebtrol（利巴韦林和Intron A）最近已被批准用于治疗至少3岁及以上儿童的丙型肝炎。 已发表的报告表明，IFN单药治疗儿童CHC的反应率高于成人。 PEG + RV是成人CHC最有效的治疗方法。 考虑到RV是一种致畸剂，并且<18岁的受试者可能对PEG单独治疗有较高的应答率，本提案的目的是进行一项随机对照试验，以比较PEG +安慰剂与PEG +RV（1：1随机化）的安全性和疗效。112名5-18岁的HCV RNA+ IFN初治儿童将入组这项多中心III期临床试验。 11个儿科中心将与NIDDK和罗氏实验室公司合作，后者将提供聚乙二醇干扰素（PegasysT），剂量为180 mcg/1.73平方米，每周x 48周，随访24周。 RV将以15 mg/kd/天p.o.给药。分开的b.i.d. (not> 1200 mg/天）X 48周，无治疗随访24周。 随机分配至PEG+安慰剂组的儿童，如果在第24周时未能表现出病毒消失（通过AmplicorT聚合酶链反应测定HCV RNA <100拷贝/ml），则将交叉至PEG+RV组（同情联合治疗组）。 这些儿童将在联合治疗24周后进行评估。 如果在联合治疗24周后未出现病毒消失，则将停用Peg-2a和RV，并对其进行密切随访24周。如果在24周的联合治疗后，他们表现出病毒消失，他们将再接受24周的治疗，并随后停止治疗24周。 在随机分配至PEG+RV组的儿童中，如果在第24周时未显示病毒消失，则将停用药物。 主要分析将基于意向治疗;主要终点将是停药24周（自基线72周）的持续病毒应答。其他终点包括生化和临床安全性评估以及身体组成和生长以及健康相关的生活质量。治疗试验将在第1年至第3年进行，并在第4年和第5年进行长期随访。因此，该试验将提供急需的数据，以指导CHC的安全有效治疗，CHC是儿童肝脏疾病的主要原因。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are approximately 150,000 infants, children, and adolescents in the United States with chronic hepatitis C virus (CHC) infection. Alpha-interferon(IFN) alone or in combination with ribavirin and pegylated interferon (PEG) in combination with RV have been approved by the FDA for use in subjects over 18 years of age. Rebtrol (ribavirn and Intron A) has recently been approved for use in treating hepatitis C in children at least 3 years of age and older. Published reports of IFN monotherapy in children with CHC have suggested that response rates are higher than in adults. PEG + RV is the most effective therapy for adults with CHC. Given that RV is a teratogen, and that subjects <18years of age may have high response rates to PEG alone, the purpose of this proposal is to perform a randomized controlled trial to compare the safety and efficacy of PEG + placebo vs. PEG +RV (1:1 randomization). 112 HCV RNA+ IFN-na¿ve children 5-18 years of age will be enrolled in this multi-center Phase III clinical trial. 11 pediatric centers will work in collaboration with the NIDDK and Roche Laboratories Inc, which will supply the pegylated interferon (PegasysT), to be given at a dose of 180mcg/1.73m2 sq week x 48 weeks, with a treatment-free follow-up of 24 weeks. RV will be given at 15 mg/kd/day p.o. divided b.i.d. (not >1200mg/day) X 48 weeks with a treatment free follow-up of 24 weeks. Children randomized to PEG+ placebo who fail to exhibit viral disappearance (HCV RNA <100copies/ml by AmplicorT polymerase chain reaction assay) at week 24 will be crossed over to PEG+RV (a compassionate combination therapy arm). These children will be assessed after 24 weeks of combination therapy. If they do not exhibit viral disappearance after 24 weeks of combination therapy, Peg-2a and RV will be stopped and they will be followed closely for 24 weeks. If after 24 weeks of combination therapy they exhibit viral disappearance, they will be treated for an additional 24 weeks and followed for 24 weeks off therpay. In children who were randomized to PEG+RV who fail to exhibit viral disappearance at week 24 the drugs will be discontinued. The primary analysis will be on an intent to treat basis; the primary endpoint will be sustained viral response 24 weeks off therapy (72 weeks from baseline). Other endpoints include biochemical and clinical safety assessments as well as body composition and growth and health related quality of life. The treatment trial will take place over years 1 through 3 with the longterm follow-up off treatment in years 4 and 5.This trial would thus provide critically needed data to guide safe and effective treatment of CHC, a major cause of liver disease in children.