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CompletedNCT01741285OLiVIAUpdated Aug 26, 2016

Effects of QVAR in Smokers With Asthma

A Phase 4 interventional study of Beclomethasone (QVAR) and Beclomethasone (Clenil) in Asthma, sponsored by University Medical Center Groningen. Completed at 1 site in Netherlands. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2016-08-26.

Sponsored by University Medical Center Groningen · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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:

Read the 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.

02

Conditions studied

  • Asthma

Keywords

  • Asthma
  • Adenosine
  • Small airways
  • Smokers
  • Ex-smokers
03

In context

Asthma

4,010 studies on the registry are indexed under Asthma; 514 are open to participants now.

This study's enrollment of 40 is below the median of 83 across 2,814 interventional studies indexed under Asthma.

Browse Asthma studies →

Lead sponsor

University Medical Center Groningen is the lead sponsor of 625 studies on the registry; 174 are open to participants now.

Browse University Medical Center Groningen studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

  • Males and females with a doctor's diagnosis of asthma
  • Age between 18 and 65 years
  • Current- and ex-smokers with ≥ 5 packyears.
  • Drop in FEV1 > 20% after provocation with small particle adenosine \< 20 mg at visit 1.

Exclusion criteria

3.2 Exclusion criteria

A subject who meets any of the following criteria will be excluded from participation in this study:

  • An asthma exacerbation during the last 6 weeks or upper respiration tract infection during the last 4 weeks prior to inclusion in the study.
  • Severe airway obstruction at baseline, FEV1 \< 50% of predicted or \< 1.2 liter.
  • Physician diagnosed predominant COPD or any other pulmonary disease that could influence the study results as judged by the investigator.
  • Pregnant or lactating women.

  • Females of childbearing potential without an efficient contraception unless they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or the use of one or more of the following acceptable methods of contraception:

    1. Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).
    2. Hormonal contraception (implantable, patch, oral, injectable).
    3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
    4. Continuous abstinence. Periodic abstinence (e.g. calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • Active comparator
    Fluticasone

    Two weeks treatment with HFA-Fluticasone 250 microgram twice daily

    Drug: Beclomethasone (QVAR) · Drug: Beclomethasone (Clenil)

  • Active comparator
    Clenil

    Two weeks treatment with HFA-Clenil 200 microgram 2 inhalations twice daily.

    Drug: Beclomethasone (QVAR) · Drug: Fluticasone

  • Experimental
    QVAR

    Two weeks treatment with QVAR 2 times 100 microgram twice daily

    Drug: Beclomethasone (Clenil) · Drug: Fluticasone

Interventions

06

What researchers measure

Primary outcomes

  1. PD20 Adenosine

    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).

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

Secondary outcomes

  1. Symptoms and Peakflow

    Twice daily symptoms (including night-time symptoms) and peakflow (PEF).

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

  2. Airway resistance

    Resistance (R5, R20, R5-R20) and Reactance at 5 Herz (X5) with IOS.

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

  3. Spirometry

    FEF25, FEF50, FEF75, FEF25-75, PEF, FEV1, FEV1/FVC, FVC/SVC

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

  4. Body Plethysmography

    RV (%predicted), TLC, RV/TLC (%), FRC, FRC/TLC (%), FRC/TLC (%predicted), IC, RV/TLC %predicted

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

  5. Peripheral blood

    cell differential counts, DNA, PBMC's, serum.

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

  6. Delta FVC during PD20 small particle adenosine.

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

  7. Questionnaires

    ACQ, BHQ, CCq

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

  8. Multiple Breath Washout Analysis

    If possiboe this measurement will be performed.

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

  9. Nasal brushing

    Genome-wide gene (mRNA and microRNA) expression and DNA methylation in nasal brushings

    Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

07

Study locations

1 site
  • University Medical Center Groningen
    Groningen, Provincie Groningen 9713GZ, Netherlands
08

References and documents

Publications

  • Cox CA, Boudewijn IM, Vroegop SJ, Schokker S, Lexmond AJ, Frijlink HW, Hagedoorn P, Vonk JM, Farenhorst MP, Ten Hacken NHT, Kerstjens HAM, van den Berge M. Associations of AMP and adenosine induced dyspnea sensation to large and small airways dysfunction in asthma. BMC Pulm Med. 2019 Jan 28;19(1):23. doi: 10.1186/s12890-019-0783-0. PubMed 30691429 ↗
09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Apr 2013, a primary completion of Jul 2015 and a completion of Dec 2015. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 27, 2012
First posted
Dec 4, 2012
Start
Apr 2013
Primary completionActual
Jul 2015
CompletionActual
Dec 2015
Last update
Aug 26, 2016
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 26, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01741285
Lead sponsor
University Medical Center Groningen
Collaborators
Teva Pharma
Responsible party
Maarten van den Berge (Chest Physician, University Medical Center Groningen) — Principal investigator
First posted
Dec 4, 2012
Start date
Apr 2013
Primary completion
Jul 2015
Completion
Dec 2015
Last update
Aug 26, 2016

Study contacts

Maarten van den Berge, MD, PhD
principal investigator · University Medical Center Groningen

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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