Comparative safety of extrafine beclometasone fixed dose combinations (FDC) and fluticasone FDC in COPD

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (R03) DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES

  DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
• Medical condition to be studied:
  Chronic obstructive pulmonary disease

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  60000

Study design details

• Main study objective:
  1. To compare the risk of pneumonia in patients with COPD among new users of ICS FDC with fine-particle fluticasone or extrafine beclometasone, and to assess if this is the same for the different fluticasone salts.2. To compare the risk of pneumonia in patients with COPD among new users of ICS FDC with extrafine beclomethasone versus long acting bronchodilators
• Outcomes:
  time until a pneumonia event, time until a respiratory infection.
• Data analysis plan:
  1. Superiority will be tested in a per protocol analysis comparing the FDC beclomethasone group with the FDC fluticasone reference group, with a superiority margin of 10% (or loge(1.1) on the log scale).2. Non-inferiority will be tested in per protocol analyses comparing the FDC beclometasone group with the LABD reference group, with a non-inferiority margin of a relative difference of 15%.A set of confounding handling approaches will be evaluated, and the best one with regard to residual bias will be chosen. Time-to-event analysis will be performed to analyse the association between treatment and time to recurrent pneumonia events. Cox regression with the Prentice, Williams and Peterson approach with gap-time will be used. To model the recurrent events, events occurring within 28 days of a previous event are considered part of a single episode. Therefore, the patients will be at risk for a new event starting 28 days after each previous event.