Effects of QVAR in Smokers With Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 4

Summary: 
      We hypothesize that extra-fine particle treatment with HFA-QVAR will be superior in improving
      small airways dysfunction, especially in ex-smokers and smokers with asthma.

      To investigate this, we will perform a study comparing the efficacy of extra-fine particle
      HFA-QVAR 200 µg b.i.d. to an equipotent dose of course particle HFA-beclomethasone
      (HFA-Clenil) 400 µg b.i.d. and with coarse particle HFA-fluticasone (GSK) 250 µg in
      ex-smokers and smokers with asthma.

      Study design: This study will be an open-label, randomised, three-way cross-over, two-center
      study. 20 smokers and 20 ex-smokers with asthma will receive the following treatments for two
      weeks:
    

Detailed description: 
      Rationale:

      Thus far, most clinical studies investigating the effects of inhaled corticosteroids (ICS) in
      asthma have concentrated on non-smoking asthmatics. However, a considerable proportion of
      asthma patients smokes. Cigarette smoke consists of ultra-fine particles with a diameter
      between 0.1 and 1 µm and therefore reaches even the smallest airways. In line with this, it
      has been reported that smoking is associated with small airways dysfunction. The latter may
      help to explain the observation that treatment with course particle inhaled corticosteroids
      is less effective in smokers with asthma. Recently, extra-fine particle aerosols such as
      hydrofluoroalkane-beclomethasone (HFA-QVAR) have become available for the treatment of
      asthma, which are more likely to reach the smaller airways. Based on the above, we
      hypothesize that extra-fine particle treatment with HFA-QVAR will be superior in improving
      small airways dysfunction, especially in ex-smokers and smokers with asthma.

      Objective: To perform a study comparing the efficacy of extra-fine particle HFA-QVAR 200 µg
      b.i.d. to an equipotent dose of course particle HFA-beclomethasone (HFA-Clenil) 400 µg b.i.d.
      and with coarse particle HFA-fluticasone (GSK) 250 µg in ex-smokers and smokers with asthma.

      Study design:

      This study will be an open-label, randomised, three-way cross-over, two-center study. 20
      smokers and 20 ex-smokers with asthma will receive the following treatments for two weeks:

      Treatment period A: 2-week treatment with HFA-QVAR (TEVA Pharma) 200 μg b.i.d. Treatment
      period B: 2-week treatment with HFA-Clenil (Chiesi) 400 μg b.i.d. Treatment period C: 2-week
      treatment with HFA-Fluticasone (GlaxoSmithKline) 250 μg b.i.d.

      Study population:

      20 smokers and 20 ex-smokers with asthma, aged 18-65 years, will receive the following
      treatments for two weeks:

      Intervention (if applicable):

      A: 2-week treatment with HFA-QVAR (TEVA) 200 μg b.i.d. B: 2-week treatment with HFA-Clenil
      (Chiesi) 400 μg b.i.d. C: 2-week treatment with HFA-Fluticasone (GlaxoSmithKline) 250 μg
      b.i.d.

      Main study parameters/endpoints: The primary end-parameter is the decrease in peripheral
      airways resistance (R5-R20) at the provocative dose of small particle adenosine causing the
      Forced Expiratory Volume in one second (FEV1) to drop with 20%. The co-primary end-parameter
      is the PD20 small particle adenosine.

      All patients will attend 7 visits to the outpatient clinic. At baseline and after treatment,
      the following investigations will be performed: PC20AMP, PD20 small particle adenosine,
      spirometry, IOS, body plethysmography, blood collection, filling in of questionnaires, and
      nasal epithelial brushings.
    

Intervention name(s): Beclomethasone (QVAR); Beclomethasone (Clenil); Fluticasone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Small particle treatment; Course particle beclomethasone; Course particle treatment
Other intervention name(s): QVAR; Clenil; Flixotide
Intervention MeSH terms: Fluticasone; Beclomethasone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Asthma; Adenosine; Small airways; Smokers; Ex-smokers