Effects of QVAR in Smokers With Asthma
- Conditions
- Asthma
- Interventions
- Registration Number
- NCT01741285
- Lead Sponsor
- University Medical Center Groningen
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Fluticasone Beclomethasone (QVAR) Two weeks treatment with HFA-Fluticasone 250 microgram twice daily Fluticasone Beclomethasone (Clenil) Two weeks treatment with HFA-Fluticasone 250 microgram twice daily Clenil Beclomethasone (QVAR) Two weeks treatment with HFA-Clenil 200 microgram 2 inhalations twice daily. Clenil Fluticasone Two weeks treatment with HFA-Clenil 200 microgram 2 inhalations twice daily. QVAR Beclomethasone (Clenil) Two weeks treatment with QVAR 2 times 100 microgram twice daily QVAR Fluticasone Two weeks treatment with QVAR 2 times 100 microgram twice daily
- Primary Outcome Measures
Name Time Method PD20 Adenosine This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone The primary end-parameter is the PD20 small particle adenosine. The co-primary objective (only in case of non-inferiority of QVAR on the primary objective) will be: Reduction in peripheral airways resistance (R5-R20) measured with IOS at the provocative dose of small particle adenosine causing the FEV1 to drop with 20% (PD20).
- Secondary Outcome Measures
Name Time Method Multiple Breath Washout Analysis This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone If possiboe this measurement will be performed.
Symptoms and Peakflow This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone Twice daily symptoms (including night-time symptoms) and peakflow (PEF).
Airway resistance This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone Resistance (R5, R20, R5-R20) and Reactance at 5 Herz (X5) with IOS.
Spirometry This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone FEF25, FEF50, FEF75, FEF25-75, PEF, FEV1, FEV1/FVC, FVC/SVC
Body Plethysmography This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone RV (%predicted), TLC, RV/TLC (%), FRC, FRC/TLC (%), FRC/TLC (%predicted), IC, RV/TLC %predicted
Peripheral blood This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone cell differential counts, DNA, PBMC's, serum.
Delta FVC during PD20 small particle adenosine. This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone Questionnaires This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone ACQ, BHQ, CCq
Nasal brushing This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone Genome-wide gene (mRNA and microRNA) expression and DNA methylation in nasal brushings
Trial Locations
- Locations (1)
University Medical Center Groningen
🇳🇱Groningen, Netherlands
University Medical Center Groningen🇳🇱Groningen, Netherlands