COPD 患者使用阿地溴铵/福莫特罗 4 周后的差异化结果：ACTIVATE 研究的重新分析。
Differential Outcomes Following 4 Weeks of Aclidinium/Formoterol in Patients with COPD: A Reanalysis of the ACTIVATE Study.
机构信息
Department of Research and Development, CIRO+, Center of Expertise for Chronic Organ Failure, Horn, the Netherlands.
NUTRIM, School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands.
出版信息
Int J Chron Obstruct Pulmon Dis. 2022 Mar 8;17:517-533. doi: 10.2147/COPD.S308600. eCollection 2022.
RATIONALE
It is difficult to predict the effects of long-acting bronchodilators (LABD) on lung function, exercise capacity and physical activity in patients with chronic obstructive pulmonary disease (COPD). Therefore, the multidimensional response to LABD was profiled in COPD patients participating in the ACTIVATE study and randomized to LABD.
METHODS
In the ACTIVATE study, patients were randomized to aclidinium bromide/formoterol fumarate (AB/FF) or placebo for four weeks. The primary outcomes included (1) lung function as measured by functional residual capacity (FRC), residual volume (RV), and spirometric outcomes; (2) exercise performance as measured by a constant work rate cycle ergometry test (CWRT); and (3) physical activity (PA) using an activity monitor. Self-organizing maps (SOMs) were used to create an ordered representation of the patients who were randomly assigned to four weeks of AB/FF and cluster them into different outcome groups.
RESULTS
A total of 250 patients were randomized to AB/FF (n = 126) or placebo (n = 124). Patients in the AB/FF group (39.6% women) had moderate-to-severe COPD, static hyperinflation (FRC: 151.4 (27.7)% predicted) and preserved exercise capacity. Six clusters with differential outcomes were identified. Patients in clusters 1 and 2 had significant improvements in lung function compared to the remaining AB/FF-treated patients. Patients in clusters 1 and 3 had significant improvements in CWRT time, and patients in clusters 2, 3 and 6 had significant improvements in PA compared to the remaining AB/FF-treated patients.
CONCLUSION
Individual responses to 4 weeks of AB/FF-treatment in COPD are differential and the degree of change differs across domains of lung function, exercise capacity and PA. These results indicate that clinical response to LABD therapy is difficult to predict and is non-linear, and show doctors that it is important to look at multiple outcomes simultaneously when evaluating the clinical response to LABD therapy.
CLINICAL TRIAL REGISTRATION
The original ACTIVATE study was registered on ClinicalTrials.gov, registration number NCT02424344.
原理
在慢性阻塞性肺疾病（COPD）患者中，预测长效支气管扩张剂（LABD）对肺功能、运动能力和身体活动的影响较为困难。因此，在参加 ACTIVATE 研究并随机分配至 LABD 的 COPD 患者中对 LABD 的多维反应进行了分析。
方法
在 ACTIVATE 研究中，患者随机分配至阿地溴铵/福莫特罗富马酸盐（AB/FF）或安慰剂治疗 4 周。主要结局包括（1）通过功能残气量（FRC）、残气量（RV）和肺活量测定评估的肺功能；（2）通过恒功率循环测功试验（CWRT）评估的运动表现；以及（3）使用活动监测仪评估的身体活动（PA）。自组织映射（SOM）用于创建随机分配至 4 周 AB/FF 治疗的患者的有序表示，并将其聚类为不同的结局组。
结果
共有 250 名患者被随机分配至 AB/FF（n = 126）或安慰剂（n = 124）。AB/FF 组（39.6%为女性）的患者患有中重度 COPD、静态过度充气（FRC：151.4（27.7）%预计值）和运动能力保持。确定了 6 个具有不同结局的聚类。与其余 AB/FF 治疗的患者相比，聚类 1 和 2 的患者的肺功能显著改善。聚类 1 和 3 的患者 CWRT 时间显著延长，聚类 2、3 和 6 的患者 PA 显著改善，与其余 AB/FF 治疗的患者相比。
结论
COPD 患者对 4 周 AB/FF 治疗的个体反应存在差异，且各领域的变化程度（包括肺功能、运动能力和 PA）也存在差异。这些结果表明，LABD 治疗的临床反应难以预测且呈非线性，在评估 LABD 治疗的临床反应时，医生同时观察多个结局非常重要。
临床试验注册
原始的 ACTIVATE 研究在 ClinicalTrials.gov 上注册，注册号为 NCT02424344。
Zotero 插件