Effects of QVAR in Smokers With Asthma (OLiVIA)

August 25, 2016 updated by: Maarten van den Berge, University Medical Center Groningen

Effects Of Extra-fine Particle HFA-becLomethasone (HFA-QVAR) Versus Course Particle Treatment In Smokers and Ex-smokers With Asthma

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:

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713GZ
        • University Medical Center Groningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Fluticasone
Two weeks treatment with HFA-Fluticasone 250 microgram twice daily
Drug: Beclomethasone (QVAR)
Small particle treatment
Other Names:
  • QVAR
Drug: Beclomethasone (Clenil)
Course particle beclomethasone
Other Names:
  • Clenil
Active Comparator: Clenil
Two weeks treatment with HFA-Clenil 200 microgram 2 inhalations twice daily.
Drug: Beclomethasone (QVAR)
Small particle treatment
Other Names:
  • QVAR
Drug: Fluticasone
Course particle treatment
Other Names:
  • Flixotide
Experimental: QVAR
Two weeks treatment with QVAR 2 times 100 microgram twice daily
Drug: Beclomethasone (Clenil)
Course particle beclomethasone
Other Names:
  • Clenil
Drug: Fluticasone
Course particle treatment
Other Names:
  • Flixotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
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.
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
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
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
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
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
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.
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
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
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Questionnaires
Time Frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
ACQ, BHQ, CCq
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
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.
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
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
This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Collaborators

Teva Pharma

Investigators

  • Principal Investigator: Maarten van den Berge, MD, PhD, University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

November 27, 2012

First Submitted That Met QC Criteria

November 30, 2012

First Posted (Estimate)

December 4, 2012

Study Record Updates

Last Update Posted (Estimate)

August 26, 2016

Last Update Submitted That Met QC Criteria

August 25, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20122011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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