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.

U 01申请SHIELD（在老年狼疮疾病中停用羟氯喹（HCQ））如下 完成R34，并由建立循证管理协议的紧迫性驱动 老年狼疮患者，一个很少受到关注的话题。需要数据来准确衡量 HCQ累积眼部暴露与疾病爆发风险之间的平衡， 比年轻患者有更多的非活动性疾病。尽管在感染方面有安全记录， 与传统的免疫抑制剂相比，HCQ视网膜毒性的风险随着持续使用而升级。 使用敏感的标准护理方法进行的评估表明，近三分之一的患者会出现视网膜病变。 损害决定停止HCQ是困难的，但临床平衡应指导这一考虑 特别是那些病情稳定并服用药物多年的患者。狼疮患者的寿命 改善，这可能会增加影响HCQ清除的合并症（例如，肾功能不全）， 预期毒性的效力会降低。在人口老龄化中，疾病活动可能会减弱， 比例进一步下降。本U 01的目的是进行一项III期、随机化、双盲安慰剂研究 一项对照、多中心、非劣效性临床试验，以探讨SLE患者停用HCQ的安全性 ≥60岁。中心假设是HCQ可以在稳定/静止的患者中安全地停用 在血清学、细胞因子和 转录组学分析研究人群为330例符合至少一种分类的患者 SLE标准（ACR、SLICC、EULAR/SLICC），≥ 60岁，目前每天至少服用200 mg HCQ， 至少7年，病情稳定。患者将被随机分配至安慰剂组或活性药物组，并接受随访。 每2个月一次，持续一年，以评估疾病活动和爆发。受试者将从纽约大学招募（Peter 伊兹米利（Izmirly）、吉尔·布永（Jill Buyon）、阿尔伯特·爱因斯坦（安娜·布罗德（Anna Broder））、HSS（简·萨尔蒙（Jane Salmon））、哥伦比亚（安卡·阿斯坎赛（Anca Askanase））、OMRF（琼 梅里尔），宾夕法尼亚州立大学（南希奥尔森）和加州大学洛杉矶分校（莫林麦克马洪）。主要结局将是 随访期间中度/重度发作。样本量基于13%中度/重度 仍接受HCQ治疗的患者的发作率，非劣效性界值等于10%的绝对差异 在群体之间。试验基础设施的建立符合NIH指南， 授予的R34的以下可交付成果：由所有研究中心的sIRB支持的模型招募;研究 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;电子数据采集系统;数据管理计划;研究药物的获取;以及 支助人员。预计这项试验将显著影响我们老年狼疮人群的护理， 提供自身免疫参数的分子景观，其可以识别适合于药物治疗的患者 调整。