Composite endpoints in COPD: clinically important deterioration in the UPLIFT trial.

ABSTRACT: BACKGROUND: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. METHODS: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??g or placebo. RESULTS:The composite endpoint included time to first confirmed decrease in trough forced expiratory volume in 1?s (FEV1) ?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 FEV1 (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. CONCLUSIONS:Composite endpoints provide additional information on COPD progression and treatment effects in clinical trials. TRIAL REGISTRATION:ClinicalTrials.gov NCT00144339 .

SUBMITTER: Rabe KF 

PROVIDER: S-EPMC7350568 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature