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 应用程序 SHIELD（在老年狼疮疾病中停止使用羟氯喹 (HCQ)）如下 完成 R34，并受到建立基于证据的管理协议的迫切需要的推动 老年狼疮患者的情况，这个话题很少受到关注，需要数据来准确权衡。 HCQ 眼部累积暴露与人群中疾病发作风险之间的平衡 尽管在感染方面有安全记录，但与年轻患者相比，他们的非活动性疾病更多。 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增加。 使用敏感的护理标准方法进行的评估表明，近三分之一的患者出现视网膜病变 停止 HCQ 的决定是困难的；但是临床平衡应该指导这一考虑。 尤其是那些病情稳定且长期服用药物的狼疮患者。 改善，这可能会增加影响 HCQ 清除率的合并症（例如肾功能不全）， 预计随着人口老龄化，疾病活动可能会减弱，从而导致毒性疗效降低。 U01 的目的是进行 III 期、随机、双盲安慰剂。 一项对照、多中心、非劣效性临床试验，旨在解决 SLE 患者停用 HCQ 的安全性 ≥60 岁的中心假设是稳定/静止期患者可以安全地停用 HCQ。 通过经过验证的疾病活动和耀斑仪器在血清学、细胞因子和 研究对象为 330 名至少满足其中一项分类的患者。 SLE 的标准（ACR、SLICC、EULAR/SLICC），年龄≥60 岁，目前每天至少服用 200 毫克 HCQ，持续至少 至少 7 岁且疾病稳定的患者将被随机分配至安慰剂组或活性组并进行随访。 一年内每 2 个月评估一次疾病活动和耀斑 受试者将从纽约大学招募（Peter）。 伊兹米利 (Jill Buyon)、阿尔伯特·爱因斯坦 (Anna Broder)、HSS (Jane Salmon)、哥伦比亚 (Anca Askanase)、OMRF (Joan) Merrill）、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）的主要结果将是该事件的发生。 随访期间中度/重度耀斑的样本量基于 13% 中度/重度的预测。 继续使用 HCQ 的患者的复发率和非劣效界值等于 10% 的绝对差异率 试验基础设施已按照 NIH 指南建立并完成。 授予的 R34 的以下成果： 由 sIRB 与所有地点研究支持的模型招募； 包含生物标志物研究和综合统计分析计划的协议； 程序；数据管理计划；研究药物的获取和培训； 预计这项试验将显着影响我们老龄化狼疮人口的护理和 提供自身免疫参数的分子景观，可以识别适合药物治疗的患者 调整。