Effects of QVAR in Smokers With Asthma

Asthma Clinical Trial

— OLiVIA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01741285
• Other study ID #: 20122011
• Status: Completed
• Phase: Phase 4
• First received: November 27, 2012
• Last updated: August 25, 2016
• Start date: April 2013
• Est. completion date: December 2015

Study information

• Verified date: August 2016
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Dutch Health Care Inspectorate
• Study type: Interventional

Clinical 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. 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:

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 information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Beclomethasone (QVAR)
Small particle treatment
• Beclomethasone (Clenil)
Course particle beclomethasone
• Fluticasone
Course particle treatment

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Teva Pharma

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone	No
Secondary	Symptoms and Peakflow	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	No
Secondary	Airway resistance	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	No
Secondary	Spirometry	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	No
Secondary	Body Plethysmography	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	No
Secondary	Peripheral blood	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	No
Secondary	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	No
Secondary	Questionnaires	ACQ, BHQ, CCq	This measurement will be performed at baseline and after two weeks treatment with either QVAR, Clenil or Fluticasone	No
Secondary	Multiple Breath Washout Analysis	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	No
Secondary	Nasal brushing	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	No