一项关于免疫球蛋白治疗预防 COPD 急性加重复发的随机双盲安慰剂对照可行性试验。
A Randomized Double-Blind Placebo-Control Feasibility Trial of Immunoglobulin Treatment for Prevention of Recurrent Acute Exacerbations of COPD.
机构信息
Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
出版信息
Int J Chron Obstruct Pulmon Dis. 2021 Dec 3;16:3275-3284. doi: 10.2147/COPD.S338849. eCollection 2021.
BACKGROUND
Observational studies suggest that immunoglobulin treatment may reduce the frequency of acute exacerbations of COPD (AECOPD).
OBJECTIVE
To inform the design of a future randomised control trial (RCT) of intravenous immunoglobulin (IVIG) treatment efficacy for AECOPD prevention.
METHODS
A pilot RCT was conducted. We recruited patients with COPD hospitalized for AECOPD, or from ambulatory clinics with one severe, or two moderate AECOPD in the previous year regardless of their serum IgG level. Patients were allocated in a 1:1 ratio with balanced randomisation to monthly IVIG or normal saline for 1 year. The primary outcome was feasibility defined as pre-specified accrual, adherence, and follow-up rates. Secondary outcomes included safety, tolerance, AECOPD rates, time to first AECOPD, quality of life, and healthcare costs.
RESULTS
Seventy patients were randomized (37 female; mean age 67.7; mean FEV1 35.1%). Recruitment averaged 4.5±0.9 patients per month (range 0-8), 34 (49%) adhered to at least 80% of planned treatments, and four (5.7%) were lost to follow-up. There were 35 serious adverse events including seven deaths and one thromboembolism. None was related to IVIG. There were 56 and 48 moderate and severe AECOPD in the IVIG vs control groups. In patients with at least 80% treatment adherence, median time to first moderate or severe AECOPD was 275 vs 114 days, favoring the IVIG group (HR 0.76, 95% CI 0.3-1.92).
CONCLUSION
The study met feasibility criteria for recruitment and retention, but adherence was low. A trend toward more robust treatment efficacy in adherent patients supports further study, but future trials must address treatment adherence.
TRIAL REGISTRATION NUMBER
NCT0290038, registered 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690038 and NCT03018652, registered January 12, 2017, https://clinicaltrials.gov/ct2/show/NCT03018652.
背景
观察性研究表明，免疫球蛋白治疗可能会减少 COPD（AECOPD）急性加重的频率。
目的
为未来静脉免疫球蛋白（IVIG）治疗 AECOPD 预防的随机对照试验（RCT）设计提供信息。
方法
进行了一项先导性 RCT。我们招募了因 AECOPD 住院的 COPD 患者，或从门诊招募了过去一年中有一次严重或两次中度 AECOPD 的患者，无论其血清 IgG 水平如何。将患者以 1:1 的比例与平衡随机分配，每月接受 IVIG 或生理盐水治疗 1 年。主要结局定义为预先指定的入组、依从性和随访率。次要结局包括安全性、耐受性、AECOPD 发生率、首次 AECOPD 时间、生活质量和医疗保健成本。
结果
70 名患者被随机分配（37 名女性；平均年龄 67.7；平均 FEV1 为 35.1%）。平均每月招募 4.5±0.9 例患者（范围 0-8），34 名（49%）至少坚持了 80%的计划治疗，4 名（5.7%）失访。有 35 例严重不良事件，包括 7 例死亡和 1 例血栓栓塞事件。没有一个与 IVIG 相关。IVIG 组和对照组分别有 56 例和 48 例中重度 AECOPD。在至少 80%治疗依从性的患者中，首次发生中重度 AECOPD 的中位时间为 275 天 vs 114 天，IVIG 组更有利（HR 0.76，95%CI 0.3-1.92）。
结论
该研究符合招募和保留的可行性标准，但依从性较低。在依从性较好的患者中，治疗效果更显著的趋势支持进一步研究，但未来的试验必须解决治疗依从性问题。
试验注册号
NCT0290038，于 2016 年 2 月 24 日注册，https://clinicaltrials.gov/ct2/show/NCT02690038 和 NCT03018652，于 2017 年 1 月 12 日注册，https://clinicaltrials.gov/ct2/show/NCT03018652。
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