AsthmaPhase 4OLiVIANCT01741285
Effects of QVAR in Smokers With Asthma
A Phase 4 study testing Beclomethasone (QVAR), Beclomethasone (Clenil) and Fluticasone in people with Asthma, run by University Medical Center Groningen at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Asthma
- What is being tested?
- Beclomethasone (QVAR), Beclomethasone (Clenil) and Fluticasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2013to Dec 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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:
- Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).
- Hormonal contraception (implantable, patch, oral, injectable).
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Medical Center Groningen
Groningen, Provincie Groningen, 9713GZ
About this study
Official title: 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:
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.
- Conditions
- Asthma
- Being tested
- Beclomethasone (QVAR), Beclomethasone (Clenil), Fluticasone
- Keywords
- Asthma, Adenosine, Small airways, Smokers, Ex-smokers
- Medical subject headings
- Asthma, Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beclomethasone (QVAR)Drug
Also called QVAR
Small particle treatment
Beclomethasone (Clenil)Drug
Also called Clenil
Course particle beclomethasone
FluticasoneDrug
Also called Flixotide
Course particle treatment
| Study group | Role | What they receive |
|---|---|---|
| Fluticasone | Active comparator | Two weeks treatment with HFA-Fluticasone 250 microgram twice daily Receives: Drug: Beclomethasone (QVAR); Drug: Beclomethasone (Clenil) |
| Clenil | Active comparator | Two weeks treatment with HFA-Clenil 200 microgram 2 inhalations twice daily. Receives: Drug: Beclomethasone (QVAR); Drug: Fluticasone |
| QVAR | Experimental | Two weeks treatment with QVAR 2 times 100 microgram twice daily Receives: Drug: Beclomethasone (Clenil); Drug: Fluticasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Secondary outcomes (9)
Symptoms and Peakflow
Twice daily symptoms (including night-time symptoms) and peakflow (PEF).
Measured: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Airway resistance
Resistance (R5, R20, R5-R20) and Reactance at 5 Herz (X5) with IOS.
Measured: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Spirometry
FEF25, FEF50, FEF75, FEF25-75, PEF, FEV1, FEV1/FVC, FVC/SVC
Measured: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Body Plethysmography
RV (%predicted), TLC, RV/TLC (%), FRC, FRC/TLC (%), FRC/TLC (%predicted), IC, RV/TLC %predicted
Measured: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Peripheral blood
cell differential counts, DNA, PBMC's, serum.
Measured: 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.
Measured: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Questionnaires
ACQ, BHQ, CCq
Measured: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Multiple Breath Washout Analysis
If possiboe this measurement will be performed.
Measured: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Nasal brushing
Genome-wide gene (mRNA and microRNA) expression and DNA methylation in nasal brushings
Measured: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2012 (estimated)
- Study startApr 2013
- Primary completionJul 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Teva Pharma
- Responsible party
- Principal investigator, Maarten van den Berge, University Medical Center Groningen
- Investigators
- Maarten van den Berge, MD, PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01741285
- Sponsor's protocol ID
- 20122011
- Acronym
- OLiVIA
- Status last verified
- Aug 2016
- First submitted
- 27 Nov 2012
- Last updated
- 26 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
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
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects Of Extra-fine Particle HFA-becLomethasone (HFA-QVAR) Versus Course Particle Treatment In Smokers and Ex-smokers With Asthma
- ClinicalTrials.gov ID
- NCT01741285
- Acronym / sponsor ID
- OLiVIA / 20122011
- Conditions
- Asthma
- Keywords
- Asthma, Adenosine, Small airways, Smokers, Ex-smokers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Teva Pharma
- Study start
- Apr 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 4 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fluticasone | Active comparator | Drug: Beclomethasone (QVAR), Drug: Beclomethasone (Clenil)Two weeks treatment with HFA-Fluticasone 250 microgram twice daily |
| Clenil | Active comparator | Drug: Beclomethasone (QVAR), Drug: FluticasoneTwo weeks treatment with HFA-Clenil 200 microgram 2 inhalations twice daily. |
| QVAR | Experimental | Drug: Beclomethasone (Clenil), Drug: FluticasoneTwo weeks treatment with QVAR 2 times 100 microgram twice daily |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beclomethasone (QVAR)Also: QVARSmall particle treatment | Drug | Clenil, Fluticasone |
| Beclomethasone (Clenil)Also: ClenilCourse particle beclomethasone | Drug | Fluticasone, QVAR |
| FluticasoneAlso: FlixotideCourse particle treatment | Drug | Clenil, QVAR |
Primary outcome
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).
9 secondary outcomes
Symptoms and Peakflow
Time frame: 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
Spirometry
Time frame: 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
Peripheral blood
Time frame: 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
Questionnaires
Time frame: 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
Nasal brushing
Time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2016.
- Derived from this study: PubMed 30691429Cox 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maarten van den Berge, MD, PhD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Beclomethasone (QVAR), Beclomethasone (Clenil) and Fluticasone in people with Asthma, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PD20 Adenosine (time frame: This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01741285, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2016.