Stopping Hydroxychloroquine In Elderly Lupus Disease (SHIELD)

停止使用羟氯喹治疗老年狼疮病 (SHIELD)

• 批准号: 10594743
• 负责人: Jill P Buyon
• 金额: $ 155.78万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594743
• 关键词: Address; Affect; Age; Age Years; Aging; American; Asian population; Attention; Autoimmune; Award; Biological Markers; Cardiovascular system; Caring; Classification; Clinical; Clinical Trials; Collaborations; Communities; Congenital Heart Block; Coupled; Data; Databases; Diagnosis; Disease; Dose; Double-Blind Method; Elderly; Eligibility Determination; End stage renal failure; Enrollment; Equilibrium; Equipoise; Estrogens; Ethics; Evaluation; Face; Flare; Funding; Grant; Guidelines; Hispanic Populations; Hydroxychloroquine; Immune; Immunosuppressive Agents; Infection; Infrastructure; Institution; Intervention; Kidney Failure; Long-Term Care for Elderly; Longevity; Lupus; Lupus Erythematosus; Maintenance; Manuals; Measurement; Modeling; Molecular; Molecular Profiling; Multi-Institutional Clinical Trial; Multicenter Studies; Observational Study; Ophthalmology; Outcome; Outcomes Research; Patient Outcomes Assessments; Patient Self-Report; Patients; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Plasma; Population; Pregnancy; Prevalence; Prevention; Procedures; Protocols documentation; Publishing; Randomized; Readiness; Recording of previous events; Regimen; Rheumatology; Risk; Role; Safety; Salmon; Sample Size; Serology; Site; Stable Disease; Statistical Data Interpretation; Surveillance Program; Surveys; Systemic Lupus Erythematosus; Time; Toxic effect; Training Support; United States National Institutes of Health; Universities; Withdrawal; aging population; arm; clinically significant; college; comorbidity; cytokine; data management; disorder risk; electronic data capture system; ethnic diversity; evidence base; experience; follow-up; improved; insight; instrument; lupus registry; medical schools; medication compliance; meetings; older patient; pharmacologic; pre-clinical; primary outcome; racial population; recruit; retinal damage; retinal toxicity; rheumatologist; senescence; socioeconomics; standard of care; transcriptomic profiling

This U01 application SHIELD (Stopping Hydroxychloroquine (HCQ) In Elderly Lupus Disease) follows completion of an R34 and is driven by the exigency to establish evidence-based protocols for the management of aging lupus patients, a topic that has received minimal attention. Data are needed to accurately weigh the balance between accumulating ocular exposure of HCQ versus the risk of disease flare in a population that may have more inactive disease than younger patients. Despite a track record of safety with regard to infection compared to traditional immunosuppressive agents, the risk of HCQ retinal toxicity escalates with continued use. Evaluation using sensitive standard of care approaches suggests nearly a third of patients accrue retinal damage. The decision to discontinue HCQ is difficult; however clinical equipoise should guide this consideration especially in patients who have been stable and on the medication for years. As the longevity of lupus patients improves, which may increase comorbidities that affect HCQ clearance (e.g., renal insufficiency), the ratio of efficacy to toxicity is expected to decrease. That disease activity may wane in the aging population drives the ratio down even further. The purpose of this U01 is to conduct a Phase III, randomized, double-blind placebo controlled, multi-center, non-inferiority clinical trial to address the safety of withdrawal of HCQ in SLE patients ≥60 years old. The central hypothesis is that HCQ can be safely discontinued in stable/quiescent patients assessed by validated disease activity and flare instruments in the context of serologic, cytokine and transcriptomic profiling. The population under study will be 330 patients who fulfill at least one of the classification criteria (ACR, SLICC, EULAR/SLICC) for SLE, are ≥60yrs, are currently taking at least 200 mg HCQ daily for at least 7yrs and have stable disease. Patients will be randomized to either the placebo or active arm and followed every 2 months for one year to assess disease activity and flares. Subjects will be recruited from NYU (Peter Izmirly, Jill Buyon), Albert Einstein (Anna Broder), HSS (Jane Salmon), Columbia (Anca Askanase), OMRF (Joan Merrill), Penn State (Nancy Olsen), and UCLA (Maureen McMahon). The primary outcome will be the occurrence of a moderate/severe flare during follow-up. Sample size is based on the projection of a 13% moderate/severe flare rate in patients remaining on HCQ and a non-inferiority margin equal to a 10% absolute difference in rates between groups. The trial infrastructure has been established in compliance with NIH guidelines and completion of the following deliverables from the awarded R34: model recruitment supported by an sIRB with all sites; study protocol with inclusion of biomarker studies and comprehensive statistical analysis plan; manual of operating procedures; electronic data capture system; data management plan; acquisition of study drugs; and training of support staff. It is anticipated that this trial will significantly impact the care of our aging lupus population and provide a molecular landscape of autoimmune parameters that may identify patients appropriate for medication adjustments.

此U01应用屏蔽（在老年狼疮疾病中停止羟氯喹（HCQ））以下 完成R34的完成，并由外来驱动，以建立基于证据的管理协议 狼疮患者的老化，这个主题受到了最少的关注。需要数据以准确加重 在累积HCQ的眼部暴露与在可能的人群中疾病爆发风险之间的平衡 与年轻患者相比，患有更多的非活性疾病。尽管有关于感染的安全记录 与传统的免疫抑制剂相比，HCQ视网膜毒性的风险持续使用。 使用敏感标准的护理方法评估表明，几乎三分之一的患者应产生残留 损害。终止HCQ的决定很困难。但是，临床平衡应该指导此考虑 特别是在稳定和药物多年的患者中。作为狼疮患者的寿命 改进，这可能会增加影响HCQ清除率的合并症（例如肾功能不全），比率 预计毒性的功效有望降低。这种疾病活动可能会在老龄化的人群中减弱 比率进一步降低。该U01的目的是进行III期，随机，双盲安慰剂 受控的，多中心的非效率临床试验，以解决SLE患者HCQ戒断的安全性 ≥60岁。中心假设是可以在稳定/静止的患者中安全停用HCQ 在血清学，细胞因子和 转录组分析。研究的人群将是330名患者，至少有一个分类 SLE的标准（ACR，SLICC，EULAR/SLICC）为≥60岁，目前每天至少服用200 mg HCQ 至少7年，患有稳定的疾病。患者将被随机分配到安慰剂或活跃的手臂上，然后遵循 每2个月一次评估疾病活动和耀斑。受试者将从纽约大学（彼得）招募 Izmirly，Jill Buyon），Albert Einstein（Anna Broder），HSS（Jane Salmon），哥伦比亚（ANCA Askanase），OMRF（Joan） 美林），宾夕法尼亚州立大学（南希·奥尔森）和加州大学洛杉矶分校（莫琳·麦克马洪）。主要结果将是发生 随访期间的现代/重度耀斑。样本量基于现代/重度13％的投影 剩余HCQ的患者的耀斑率和非效率边缘等于10％的绝对差异 两组之间。试验基础设施已根据NIH指南和完成建立 在授予R34的以下可交付成果中，由所有站点的SIRB支持的模型招聘；学习 包括生物标志物研究和综合统计分析计划的方案；操作手册 程序；电子数据捕获系统；数据管理计划；获得研究药物；和培训 支持人员。预计该试验将对我们老龄化狼疮人群的护理产生重大影响，并 提供自身免疫参数的分子景观，该景观可能识别适合药物的患者 调整。