Efficacy and Safety of ICS/LABA vs. LAMA/LABA in Patients With Different COPD Phenotypes.
Condition: COPD
MeSH terms: Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a randomized, blinded, controlled clinical trial for mexican COPD patients.

      Biomass smoke associated COPD (BS-COPD) clinical spectrum is different to the one seen in
      tobacco smoke associated COPD (TS-COPD). BS-COPD patients present COPD-asthma phenotype or
      asthma-COPD overlap syndrome (ACOS), TS-COPD patients present mostly the emphysema phenotype.
      BS-COPD patients have a greater risk of exacerbations in comparison to the emphysema
      phenotype. Therefore, individualizing treatment in both phenotypes may be very useful among
      the clinical practitioners.

      The investigators expect treatment with FF/V to be superior in preventing COPD exacerbations
      than the U/V combination in patients with COPD-asthma phenotype; andU/V to be superior than
      FF/V in patients with the emphysema phenotype.

      The general objective of the study is to determine the exacerbations outcome in patients with
      COPD-asthma vs emphysema phenotype patients, treated with both drugs. Secondary objectives
      include assessment of pulmonary function tests, quality of life, dyspnea and functional
      capacity change after a 24 weeks treatment.
    

Detailed description: 
      Type and duration of the investigation: A randomized, blinded, controlled clinical trial;
      longitudinal, prospective, 3 years (Sep-2017 through Sep-2020).

      Background: COPD associated to biomass smoke (BS-COPD) represents the third of all COPD cases
      in Latin America, and almost the 2% in general population prevalence studies. BS-COPD
      clinical spectrum is different to the one seen in COPD associated to tobacco smoke (TS-COPD).
      While BS-COPD patients present COPD-asthma phenotype or asthma-COPD overlap syndrome (ACOS),
      TS-COPD patients present mostly the emphysema phenotype.

      COPD-asthma phenotype in BS-COPD, probably explains that they have a greater risk of
      exacerbations in comparison to the emphysema phenotype. Therefore, individualizing treatment
      in both phenotypes may be very useful among the clinical practitioners, because even though
      those patients are not included in traditional clinical trials, they are part of every day's
      practice.

      In this sense, providing a specific treatment in this group of patients could change the
      disease progression, improving symptoms, quality of life, reducing costs, side effects and
      exacerbations. The investigators hypothesize that COPD-asthma phenotype or asthma-COPD
      overlap syndrome (ACOS), may get a greater benefit by using a combination LABA/ICS
      (Fluticasone Furoate/Vilanterol - FF/V) therapy, whereas those with the emphysema phenotype
      with LABA/LAMA (Umeclidinium/Vilanterol U/V) therapy

      The upside of these drugs is that both of them have the same easy-to-use device, and it is
      inhaled once a day only. Their efficacy and safety have been tested in TS_COPD but not in
      BS-COPD. This trial will allow us to have a clinically and functionally characterization
      (using biological markers) of the BS-COPD phenotype and to compare those patients with those
      with the emphysema phenotype.

      Hypothesis: Treatment with FF/V will be superior in preventing COPD exacerbations than the
      U/V combination in patients with COPD-asthma phenotype; while U/V will be superior than FF/V
      in patients with the emphysema phenotype.

      General objective: To determine the exacerbations outcome (exacerbations free interval,
      exacerbations frequency, severe exacerbations that needed hospitalization frequency,
      exacerbations frequency according to absolute and percentage (>3%) blood eosinophils,
      exacerbations percentage for emphysema phenotype and COPD-asthma phenotype) in patients with
      COPD-asthma vs emphysema phenotype patients, treated with Fluticasone Furoate/Vilanterol
      100/25 mcg/day vs Umeclidinium/Vilanterol 55/25 mcg/day, after 6 months of treatment.

      Secondary objectives: To determine in both groups: (1) Pulmonary function change (FEV1, FVC
      and inspiratory capacity) (2) Impulse oscillometry resistance change (3) FeNO change (5)
      Quality of life change (CAT and Saint George) (6) Dyspnea change (mMRC, BDI y TDI) (7)
      Functional capacity change (6MWT distance). (8) To characterize and establish the frequency
      of the COPD-asthma phenotype in BS-COPD patients and emphysema-phenotype in TS-COPD patients.

      Methods: Randomized double blind controlled clinical trial. Patients with at least one
      exacerbation in the last 12 months (confirmed by the prescription of antibiotic and/or oral
      steroid), and a smoking index > 10 packs/year or a biomass smoke exposition index > 100
      hours/year. One hundred BS-COPD patients and one hundred TS-COPD patients will be included;
      both groups will be exposed to the two treatment options. Fifty patients from each group
      (BS-COPD and TS-COPD) will be assigned with FF/V and 50 from each group with U/V. Emphysema
      phenotype and air-trapping pattern will be determined with a CT image. All CTs will be
      assessed by a radiologist. Baseline DLco will also be correlated with the emphysema CT
      findings. Blood eosinophils, blood levels IgE, bronchodilator reversibility and baseline
      FeNO. Rate of exacerbations will be determined in both groups for a time period of 6 months.
      At the end of the study, the phenotype of each patient will be determined and treatment
      efficacy will be evaluated according to the phenotype. The sample size was chosen
      conventionally by considering that there are no other centers with a BS-COPD cohort.
      Treatment will be randomly assigned using a random numbers table. Safety evaluation includes
      severe adverse events (SAE) assessment (mainly pneumonia). During the informed consent
      signing visit (day -15), BS-COPD or TS-COPD diagnosis will be confirmed. There will be four
      in-clinic visits (baseline; +30 days; +90 days and +180 days) where the symptoms diary will
      be evaluated to determine the rate of exacerbations or other health resources use. Also,
      pulmonary function tests (spirometry pre and post-BD, IC) and functional capacity tests
      (6MWT) will be performed by each patient. Health related quality of life (SGRQ and CAT) and
      dyspnea (mMRC and BDI/TDI) questionnaires will also performed. There will be three telephonic
      visits (+60 days, +120 days, +210 days) where adverse events, concomitant medication, other
      health resources use and exacerbations since last visit will be assessed.
    

Intervention name(s): Fluticasone Furoate/Vilanterol 100/25 mcgs; Umeclidinium/Vilanterol 62.5/25 mcgs
Intervention type(s): Drug; Drug
Intervention description(s): Dry powder inhaler with 30 blisters. 100/25mcgs a day for 24 weeks.; Dry powder inhaler with 30 blisters. 62.5/25mcgs a day for 24 weeks
Other intervention name(s): Relvare; Anoro
Intervention MeSH terms: Fluticasone; Xhance
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Chronic obstructive pulmonary disease; Biomass; Tobacco; COPD treatment; COPD phenotypes