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

Respir Res. 2020 Jul 9;21(1):177. doi: 10.1186/s12931-020-01431-y.

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 μg 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 .

Keywords: Exacerbations; Lung function; Tiotropium.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Bronchodilator Agents / therapeutic use
  • Clinical Deterioration
  • Clinical Trials as Topic
  • Double-Blind Method
  • Endpoint Determination / methods*
  • Female
  • Forced Expiratory Flow Rates
  • Forced Expiratory Volume
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Research Design
  • Respiratory Function Tests
  • Surveys and Questionnaires
  • Tiotropium Bromide / therapeutic use

Substances

  • Bronchodilator Agents
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT00144339