PEDIATRIC LATE OUTCOMES PROTOCOL

儿科晚期结果方案

• 批准号: 7375575
• 负责人: GRAEME S WILSON
• 金额: $ 0.44万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375575
• 关键词: PEDIATRIC; LATE; OUTCOMES; PROTOCOL

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. The purpose of this study is to follow children and adolescents who are currently enrolled in or were previously enrolled in pediatric ACTG treatment perinatal or drug research studies to look for any late consequences of therapy in growth, neurologic and neuropsychologic function, long term survival, and quallity of life. The child is eligible for this study if the child is currently enrolled in, or was previously enrolled in a pediatric ACTG protocol or is currently enrolled in the Long Term Survivors of the Pediatric AIDS Foundation study being conducted at an ACTG site. This includes infants born to HIV infected mothers who were enrolled in an ACTG drug study when they were pregnant, regardless of whether or not definite HIV infection status in the infant is known. All children are eligible to be followed until their 21st birthday. There are several key hypotheses listen below that this late outcomes protocol plans to address in relation to pediatric interventions. In addition, it is also anticipated that the longitudinal data gathered in this protocol will enable investigators in the pediatric ACTG to answer other research questions and hypotheses specific to treatment in perinatal protocols in which they are involved. Perinatal Group: There will be no signficiantly increased prevalence of late organ abnormality/toxicity (focus on system with high mitochondrial contact - heart, liver, muscle), birth defects or neoplasms (i.e. vaginal tumor, pap smear abnormality) among ultimately uninfected infants exposed to zidovudine (or other study treatments) in utero compared to prevalence rates among comparable pediatric populations in the United States who were not exposed in utero to zidovudine (or other study treatments). For infants enrolled in ACTG 076, the comparison to prevalence rates will be for uninfected children who received placebo. For other future studies, comparison to national prevalence rates may need to be used. Among uninfected infants on ACTG 076, there will be no significant differences in growth or development among infants whose mothers received ZDV compared to those whose mother's received placebo during pregnancy: a.) growth (weight, height, head circumference) b.) pubertal development (Tanner staging, age of first menses) c.) mean neurocognitive scores on Bayley and later cognitive tests. Among infected children from ACTG 185, there will be no difference in disease progession betweent hose whose mothers received HIVIG compared to those whose mothers received IVIG. Disease progression is defined by clinical (i.e. AIDS-defining illness, death), immunologic (i.e. age-adjusted CD4+count), and virologic (quantitative central load via testing of ACTG 219 stored specimens, test to be determined) parameters. HIV Infected Group: There will be differences in rates of long term cumulative dose-related drug specific organ system toxicities related to specific drug therapies. For example, hepatic, cardiac or muscle toxicity will be more likely to occur with chronic ZDV therapy compared to other antiretroviral therapies; peripheral neuropathy will be more likely to be seen with chronic ddI, or ddC use; and ddI, ddC or 3TC will be more likely to be associated with pancreatic abnormalities. Initial combination therapy as compared to montherapy (e.g., using a randomization treatment protocol such as ACTG 152, 239 and 300) will result in significantly increased long term survival and improved physical growth and quality of life, as measured by length of survival, mean growth percentiles for height, weight and head circumference, and median scores on quality of life instruments. Initial use of combination therapy in infancy (0-24 months) (e.g., ACTG 152 or 239) will result in fewer neurology diagnoses and signficiantly higher mean neurocognitive scores at age 4 and 7 years compared to initial use of antiretroviral monotherapies. For children from Protocol 128 (followed up at 5-7 years post enrollment on 128) there will continue to be no significant differences in neurocognitive scores on the WISC-R between treatment arms. Advances in drug/biologic interventions, prophylaxis and treatment regimens for opportunistic infecious diseases and improved supportive care over time will result in significantly increased survival, improved growth adn development, decreased morbidity, and improved quality of life for successive cohorts of children involved in ACTG protocols. This will be assessed by comparing survival, median growth percentiles, median CD4+ percentages and quality of life scores at ages 2, 4, 7, 15, and 20 years for successive cohorts (e.g., assessed serially every 3 to 5 years) of pediatric subjects exposed to drugs/biologics in ACTG protocols.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心机构，不一定为研究者机构。本研究的目的是随访目前参加或以前参加过儿科ACTG治疗围产期或药物研究的儿童和青少年，以寻找治疗对生长、神经和神经心理功能、长期生存和生活质量的任何晚期后果。如果儿童目前已入组或之前已入组儿科ACTG方案，或目前已入组正在ACTG研究中心进行的儿科艾滋病基金会长期生存者研究，则该儿童有资格参加本研究。这包括HIV感染母亲所生的婴儿，这些母亲在怀孕时参加了ACTG药物研究，无论婴儿的HIV感染状态是否明确。所有的孩子都有资格被跟踪到他们的21岁生日。有几个关键的假设听下面，这个后期结果协议计划解决有关儿科干预。此外，还预计本方案中收集的纵向数据将使儿科ACTG的研究者能够回答他们参与的围产期方案中特定治疗的其他研究问题和假设。围产期组：晚期器官异常/毒性的患病率不会显著增加（重点关注线粒体接触率高的系统-心脏、肝脏、肌肉）、出生缺陷或肿瘤（即阴道肿瘤，在接触齐多夫定的最终未感染婴儿中，（或其他研究治疗）与在子宫内未暴露于齐多夫定（或其他研究治疗）的美国可比儿科人群的患病率相比。对于入组ACTG 076的婴儿，将与接受安慰剂的未感染儿童的患病率进行比较。对于今后的其他研究，可能需要与国家流行率进行比较。在接受ACTG 076的未感染婴儿中，与母亲在妊娠期间接受安慰剂的婴儿相比，母亲接受ZDV的婴儿的生长或发育将没有显著差异：a）生长（体重、身高、头围）B.）青春期发育（坦纳分期，第一次月经的年龄）c.）贝利和后来的认知测试的平均神经认知分数。在来自ACTG 185的感染儿童中，母亲接受HIVIG的儿童与母亲接受IVIG的儿童之间的疾病进展没有差异。疾病进展由临床（即AIDS定义疾病、死亡）、免疫学（即年龄校正的CD 4+计数）和病毒学（通过检测ACTG 219储存标本定量中心负荷，检测待定）参数定义。HIV感染者：与特定药物治疗相关的长期累积剂量相关药物特异性器官系统毒性的发生率将存在差异。例如，与其他抗逆转录病毒治疗相比，ZDV长期治疗更可能发生肝脏、心脏或肌肉毒性;长期使用ddI或ddC更可能观察到周围神经病变; ddI、ddC或3 TC更可能与胰腺异常相关。初始联合治疗与单药治疗相比（例如，使用随机化治疗方案，如ACTG 152、239和300）将导致显著增加的长期存活率和改善的身体生长和生活质量，如通过存活时间、身高、体重和头围的平均生长曲线以及生活质量工具的中值评分所测量的。在婴儿期（0-24个月）首次使用联合治疗（例如，ACTG 152或239）将导致更少的神经学诊断和显着更高的平均神经认知评分在4岁和7岁相比，最初使用抗逆转录病毒单药治疗。对于来自方案128的儿童（在128入组后5-7年随访），治疗组之间WISC-R的神经认知评分将继续无显著差异。随着时间的推移，药物/生物干预、机会性感染疾病的预防和治疗方案以及支持性护理的改善将显著提高参与ACTG方案的连续队列儿童的生存率、改善生长发育、降低发病率和改善生活质量。这将通过比较连续队列在2岁、4岁、7岁、15岁和20岁时的生存率、中位生长指数、中位CD 4+百分比和生活质量评分来评估（例如，每3 - 5年进行一次连续评估）。