Assessment of dyspnea and other symptoms as patient reported outcomes (PRO) in patients with chronic obstructive pulmonary disease (COPD), symptomatic on LABA/ICS maintenance therapy (now) treated with Spiolto® Respimat® (tiotropium/olodaterol) in comparison to open or fixed triple combination treatment in routine clinical practice (EVELUT)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

  Evaluation of patient-reported outcomes
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  SPIOLTO RESPIMAT
• Anatomical Therapeutic Chemical (ATC) code:
  (R03AL06) olodaterol and tiotropium bromide

  olodaterol and tiotropium bromide
• Medical condition to be studied:
  Chronic obstructive pulmonary disease

Population studied

• Short description of the study population:
  Main inclusion criteria:; • ≥40 years old COPD patients symptomatic regarding dyspnea ; (mMRC Dyspnea score ≥1) AND regarding symptoms (CATTM; Score ≥10) at the same time; • Patients on LABA/ICS maintenance therapy switched to Spiolto®; Respimat® or a free/fixed triple combination of LAMA + LABA + ; ICS at Visit 1 at the discretion of the treating physician.; Main exclusion criteria:; • Patients with contraindications acc. to SmPC ; • Acute exacerbation of COPD (within 4 weeks prior to Visit 1); • Frequently exacerbating patients, i. e. patients with ≥2 moderate ; exacerbations within the last 12 months or ≥1 exacerbation leading ; to hospitalization within the last 12 months; • Acute respiratory failure (pH <7,35 and / or respiratory rate >30/min ; within 3 months prior to Visit 1); • History or current diagnosis of asthma and asthma-COPD overlap, ; history of allergic rhinitis within the last 5 years
• 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:
  900

Study design details

• Study design:
  Open-label comparative multicentric cohort study
• Main study objective:
  The primary objective of this NIS is to investigate the changes in dyspnea (as measured via mMRC questionnaire) and symptom burden (as measured via CAT) in COPD patients dyspneic despite LABA/ICS maintenance treatment when switched to either Spiolto® Respimat® in the new reusable inhaler inhaler or to any triple therapy (free or fixed-dosed).
• Outcomes:
  Two primary endpoints will be assessed: ; Difference in mMRC (modified Medical Research Council) score at baseline and after end of observation (approx. 12 weeks of treatment, Visit 2) Difference in CATTM (COPD assessment test) score at baseline and after end of observation (approx.. 12 weeks of treatment, Visit 2), ; • patients’ general condition according to the Physician’s Global Evaluation (PGE) score at baseline and end of the observation period of approximately 12 weeks, ; • patient satisfaction with inhaler and therapy at end of observation period according to a seven-point ordinal scale (ranging from very dissatisfied to very satisfied) ; • proportion of responders with mMRC ≥1 and with CAT ≥2
• Data analysis plan:
  The estimation of the relative treatment effect concerning the primary outcomes is subject to potential confounding, therefore adjusted analyses are required and will be performed. Multiple analytical approaches will be applied to allow an assessment of the sensitivity of the results to these approaches: ; • Propensity score matching (primary analysis, requires data to be discarded from the analysis) ; • Propensity score weighting (uses the complete data set) ; • Multivariable regression modeling (uses the complete data set) ; The relative treatment effect will be determined based on model coefficients (along with 95% confidence intervals) and statistical testing of these coefficients. Since the study is exploratory, no multiplicity adjustment is planned.