NAC Attack, a phase-3, multicenter, randomized, placebo-controlled trial in patients with retinitis pigmentosa

摘要：视网膜色素变性（RP）是一种遗传性视网膜变性， 基因突变的数量。它是20-60岁人群失明和严重视力丧失的主要原因 年RP的第一个症状是由于突变引起的杆细胞死亡而导致的夜间视力丧失 光感受器随后的视锥光感受器的丧失导致视野逐渐收缩， 最终失明。目前，没有预防RP视力丧失的治疗方法。NAC攻击是第3阶段 多中心、随机、双盲、平行、安慰剂对照临床试验，以评价疗效 和口服N-乙酰半胱氨酸（NAC）在RP患者中的安全性。受试者将被随机分配接受 以2：1的比例口服NAC 1800 mg/bid或安慰剂，并将随访45个月。 协调中心（CC）与执行委员会密切合作，以确保成功 NAC攻击CC有助于研究领导，并提供试验设计、促进 招募和保留参与者，协调所有试验实体，实施和维护 高质量的数据管理系统、统计分析和质量保证。协调委员会将： 招募并保留具有经验丰富的研究者和足够招聘能力的临床研究中心; 确保临床研究中心人员完成认证要求并符合法规要求; 通过设计和实施数据收集表格，创建和维护研究数据库， 使用REDCap进行基于网络的数据采集、数据编辑和数据管理; 使用JHU OneDrive创建和维护基于云的研究门户，以接收和管理成像， 临床研究中心的测试文件; 建议临床研究中心解决实时问题和成功实施的总体策略 研究方案; 为临床研究中心提供研究管理辅助工具，如预约时间表、即将到来的 访视、表格缺失和研究材料提交不完整; 定期向临床研究中心和所有研究委员会提供研究进展和性能报告; 设计和实施一个完整的质量保证活动计划，包括人员认证， 临床研究中心、研究中心访视和性能监测; 提供研究数据的中期和最终统计分析; 3.准备各种委员会和学习会议; 参与并领导科学演示和报告的编写。 NAC攻击有可能确定一种使所有RP患者受益的药物治疗，无论 其致病突变的鉴定，从而影响RP的临床管理。

ABSTRACT: Retinitis Pigmentosa (RP) is an inherited retinal degeneration caused by one or more of a large number of genetic mutations. It is a major cause of blindness and severe vision loss in people aged 20-60 years. The first symptom in RP is loss of night vision as a result of mutation-caused death of rod photoreceptors. Subsequent loss of cone photoreceptors leads to gradual constriction of visual field and eventually blindness. Currently, there is no treatment for preventing vision loss in RP. NAC Attack is a phase-3 multicenter, randomized, double masked, parallel and placebo-controlled clinical trial to evaluate the efficacy and safety of oral N-acetylcysteine (NAC) in patients with RP. Participants will be randomized to receive either oral NAC of 1800mg/bid or placebo in a ratio of 2:1 and will be followed for 45-months. The Coordinating Center (CC) collaborates closely with the Executive Committee to ensure the success of NAC Attack. The CC contributes to study leadership and provides expertise on trial design, facilitation of recruitment and retention of participants, coordination across all trial entities, implementation and maintenance of a high-quality data management system, statistical analysis, and quality assurance. The CC will:  Enlist and retain Clinical Sites with experienced investigators and sufficient recruitment capacity;  Ensure that Clinical Site personnel complete certification requirements and are in regulatory compliance;  Create and maintain the study database through design and implementation of data collection forms, secure web-based data capture using REDCap, data editing, and data management;  Create and maintain the study cloud-based portal using JHU OneDrive to receive and manage imaging and test files from the clinical sites;  Advise Clinical Sites on resolution of real-time problems and overall strategies for successful implementation of the study protocol;  Provide aids to clinical sites for study management such as appointment schedule, reminders of upcoming visits, missing forms, and incomplete submission of study materials;  Provide regular reports on study progress & performance to Clinical Sites and all study committees;  Design and implement a full program of quality assurance activities including certification of personnel and clinical sites, site visits, and performance monitoring;  Provide interim and final statistical analyses of study data;  Prepare for various committee and study meetings;  Participate and lead in the preparation of scientific presentations and reports. NAC Attack has the potential to identify a pharmacological therapy benefitting all patients with RP, irrespective of the identification of their causative mutation, and thus to impact on the clinical management of RP.