Member of the German Center for Lung Research (DZL), LungClinic Grosshansdorf, Wöhrendamm 80, 22927, Grosshansdorf, Germany.
Member of the German Center for Lung Research (DZL), Christian Albrechts University Kiel, Kiel, Germany.
Respir Res. 2020 Jul 9;21(1):177. doi: 10.1186/s12931-020-01431-y.
Assessments of lung function, exacerbations and health status are common measures of chronic obstructive pulmonary disease (COPD) progression and treatment response in clinical trials. We hypothesised that a composite endpoint could more holistically assess clinically important deterioration (CID) in a COPD clinical trial setting.
A composite endpoint was tested in a post hoc analysis of 5652 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2-4 COPD from the 4-year UPLIFT study. Patients received tiotropium 18 μg or placebo.
The composite endpoint included time to first confirmed decrease in trough forced expiratory volume in 1 s (FEV) ≥100 mL, confirmed increase in St. George's Respiratory Questionnaire (SGRQ) total score ≥ 4 units, or moderate/severe exacerbation. Most patients (> 80%) experienced CID, with similar incidence among GOLD subgroups. Most confirmed trough FEV (74.6-81.6%) and SGRQ (72.3-78.1%) deteriorations were sustained across the study and in all GOLD subgroups. Patients with CID more frequently experienced subsequent exacerbation (hazard ratio [HR] 1.79; 95% confidence interval [CI] 1.67, 1.92) or death (HR 1.21; 95% CI 1.06, 1.39) by Month 6. CID was responsive to bronchodilator treatment.
Composite endpoints provide additional information on COPD progression and treatment effects in clinical trials.
ClinicalTrials.gov NCT00144339 .
在临床试验中，评估肺功能、加重情况和健康状况是评估慢性阻塞性肺疾病（COPD）进展和治疗反应的常见指标。我们假设复合终点可以更全面地评估 COPD 临床试验中的临床重要恶化（CID）。
在为期 4 年的 UPLIFT 研究中，对全球慢性阻塞性肺疾病倡议（GOLD）2-4 级 COPD 的 5652 例患者进行了一项事后分析，对复合终点进行了测试。患者接受噻托溴铵 18μg 或安慰剂治疗。
复合终点包括首次确认的 1 秒用力呼气量（FEV）谷值下降≥100mL、圣乔治呼吸问卷（SGRQ）总分增加≥4 分或中度/重度加重的时间。大多数患者（>80%）发生 CID，GOLD 亚组的发生率相似。大多数确认的 FEV 谷值（74.6-81.6%）和 SGRQ（72.3-78.1%）恶化在整个研究过程中持续存在，并且在所有 GOLD 亚组中都存在。CID 患者更频繁地经历随后的加重（危险比 [HR] 1.79；95%置信区间 [CI] 1.67，1.92）或在第 6 个月死亡（HR 1.21；95% CI 1.06，1.39）。CID 对支气管扩张剂治疗有反应。
复合终点为临床试验中 COPD 进展和治疗效果提供了额外的信息。
ClinicalTrials.gov NCT00144339。
