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Effects of QVAR in Smokers With Asthma (OLiVIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01741285
Recruitment Status : Completed
First Posted : December 4, 2012
Last Update Posted : August 26, 2016
Sponsor:
Collaborator:
Teva Pharma
Information provided by (Responsible Party):
Maarten van den Berge, 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:


Condition or disease Intervention/treatment Phase
Asthma Drug: Beclomethasone (QVAR) Drug: Beclomethasone (Clenil) Drug: Fluticasone Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects Of Extra-fine Particle HFA-becLomethasone (HFA-QVAR) Versus Course Particle Treatment In Smokers and Ex-smokers With Asthma
Study Start Date : April 2013
Actual Primary Completion Date : July 2015
Actual Study Completion Date : December 2015


Arm Intervention/treatment
Active Comparator: Fluticasone
Two weeks treatment with HFA-Fluticasone 250 microgram twice daily
Drug: Beclomethasone (QVAR)
Small particle treatment
Other Name: QVAR

Drug: Beclomethasone (Clenil)
Course particle beclomethasone
Other Name: Clenil

Active Comparator: Clenil
Two weeks treatment with HFA-Clenil 200 microgram 2 inhalations twice daily.
Drug: Beclomethasone (QVAR)
Small particle treatment
Other Name: QVAR

Drug: Fluticasone
Course particle treatment
Other Name: Flixotide

Experimental: QVAR
Two weeks treatment with QVAR 2 times 100 microgram twice daily
Drug: Beclomethasone (Clenil)
Course particle beclomethasone
Other Name: Clenil

Drug: Fluticasone
Course particle treatment
Other Name: Flixotide




Primary Outcome Measures :
  1. PD20 Adenosine [ Time Frame: 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 :
  1. Symptoms and Peakflow [ Time Frame: 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).

  2. Airway resistance [ Time Frame: 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.

  3. Spirometry [ Time Frame: 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

  4. Body Plethysmography [ Time Frame: 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

  5. Peripheral blood [ Time Frame: 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.

  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 [ Time Frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone ]
    ACQ, BHQ, CCq

  8. Multiple Breath Washout Analysis [ Time Frame: 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.

  9. Nasal brushing [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

3.1 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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01741285


Locations
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Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713GZ
Sponsors and Collaborators
University Medical Center Groningen
Teva Pharma
Investigators
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Principal Investigator: Maarten van den Berge, MD, PhD University Medical Center Groningen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Maarten van den Berge, Chest Physician, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT01741285    
Other Study ID Numbers: 20122011
First Posted: December 4, 2012    Key Record Dates
Last Update Posted: August 26, 2016
Last Verified: August 2016
Keywords provided by Maarten van den Berge, University Medical Center Groningen:
Asthma
Adenosine
Small airways
Smokers
Ex-smokers
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Beclomethasone
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists