Qvar Versus Clenil, a General Practice Research Database Study

Asthma Clinical Trial

Official title:

HFA Beclomethasone in Asthma, a General Practice Research Database Study: Real-life Observational Evaluation of Extra-fine With Standard Particle Size Beclometasone Dipropionate Using the Propellant Hydrofluoroalkane 134a for the Management of Asthma in a Representative UK Primary Care Population

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01400217
• Other study ID #: 007/11
• Status: Completed
• Phase: N/A
• First received: July 20, 2011
• Last updated: October 29, 2012
• Start date: January 1991
• Est. completion date: October 2010

Study information

• Verified date: October 2012
• Source: Research in Real-Life Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Observational

Clinical Trial Summary

This study will compare the absolute and relative effectiveness of asthma management in patients on inhaled corticosteroid (ICS) maintenance therapy as either extra-fine-particle or larger-particle formulation beclomethasone dipropionate (BDP) via metered-dose inhalers (MDIs) using the propellant hydrofluoroalkane propellant (HFA-BDP), namely Qvar® MDI compared with Clenil® MDI.

Description:

Current asthma guidelines in the UK are underpinned by evidence derived from randomised controlled trials (RCTs). Although RCT data are considered the gold standard, patients recruited to asthma RCTs are estimated to represent less than 10% of the UK's asthma population. The poor representation of the asthma population is due to a number of factors, such as tightly-controlled inclusion criteria for RCTs. There is, therefore, a need for more representative RCTs and real-life observational studies to inform existing guidelines and help optimise asthma outcomes.

In response to the Montreal Protocol's ruling to phase out ozone-depleting chlorofluorocarbon (CFC) propellants in asthma inhalers, several hydrofluoroalkane-134a-propellant (HFA-) formulations of BDP have been developed. Two branded generic formulations currently available in the UK are Qvar® (Teva Pharmaceutical Industries Ltd) - an extra-fine-particle (~1.1 microns) HFA-BDP (solution) formulation and Clenil® (Chiesi Limited) - a larger particle (~2.9 microns) HFA-BDP (suspension) formulation.

The extra-fine particle formulation HFA-BDP formulation (Qvar®) has been shown to improve total and small airway deposition relative to CFC-BDP. As a result of the more even distribution through both the large and small airways of the lungs and data from short-term randomised clinical trials (RCTs), Qvar® dosing is recommended at approximately one half the dose of traditional CFC-BDP (average particle size ~3.5 microns). However, the larger-particle Clenil® is recommended for prescribing at the same dose as traditional CFC-BDP.

Further studies are required to understand whether the differences in particle size and airway distribution have an impact on asthma outcomes over the long-term.

This observational study will investigate the real-world effectiveness of extra-fine HFA-BDP (Qvar®) as compared with larger-particle HFA-BDP (Clenil®) in patients with asthma who: were new to ICS therapy; received an increase in their ICS dose, or switched / changed baseline ICS therapy to HFA-BDP with no change in BDP-equivalent ICS dose. We hypothesise that differences in effectiveness might become apparent over the longer term through a retrospective database analysis of one-year outcomes for the diverse patient population seen in primary care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56985
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 80 Years

Eligibility

Inclusion Criteria:

• Aged: 4-80 years

• Paediatric cohort (aged 4-11 years), and

• Adult cohort (aged 12-80 years )

• Evidence of asthma and current asthma therapy:

• All cohorts (IPDI, IPDS, IPDA):

• a diagnostic code for asthma, and / or *=2 prescriptions for asthma at different points in time during the prior year and/or IPDI only: =2 prescriptions for asthma therapies during the outcome year, including =1 ICS prescription in addition to that received at IPD

IPDA and IPDS only:

• 1 ICS prescription in the baseline year, and

• 1 other asthma prescription during the baseline year.

*Evidence of "current therapy":

• 2 prescription for ICS during the outcome year (i.e. =1 prescription in addition to the prescription at index date

• Have at least one year of up-to-standard (UTS) baseline data (prior to the IPD) and at least one year of UTS outcome data (following the IPD).

Exclusion Criteria:

• Had a COPD read code at any time; and/or

• Had any chronic respiratory disease, except asthma, at any time; and/or

• Patients on maintenance oral steroids during baseline year

• Received a combination inhaler in addition to a separate ICS inhaler in the baseline year; and/or

• Received ICS therapy during baseline year via DPI (IPDA and IPDS cohorts only).

• If they received multiple ICS prescriptions on the same day at IPD or immediately before

Study Design

Observational Model: Case Control, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• extra fine particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler
IPDI cohort intervention = initiation of intervention drug; IPDS cohort intervention = switching from baseline inhaled corticosteroid therapy to intervention drug without a change in baseline inhaled corticosteroid dose; IPDA cohort intervention = increase in baseline inhaled corticosteroid drug as intervention drug
• standard particle particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler
IPDI cohort intervention = initiation of intervention drug; IPDS cohort intervention = switching from baseline inhaled corticosteroid therapy to intervention drug without a change in baseline inhaled corticosteroid dose; IPDA cohort intervention = increase in baseline inhaled corticosteroid drug as intervention drug

Locations

Country	Name	City	State
United Kingdom	Research in Real Life Ltd	Cawston	Norfolk

Sponsors (2)

Lead Sponsor	Collaborator
Research in Real-Life Ltd	Teva Pharmaceutical Industries

Country where clinical trial is conducted

United Kingdom, 

References & Publications (11)

Appleton SL, Adams RJ, Wilson DH, Taylor AW, Ruffin RE; North West Adelaide Cohort Health Study Team. Spirometric criteria for asthma: adding further evidence to the debate. J Allergy Clin Immunol. 2005 Nov;116(5):976-82. — View Citation

AS Institute Inc. 2010. Statistical Analysis with SAS/STAT Software. Available online at: www.SAS.com/offices/europe/uk/technologies/analytics/statistics/stat/ondex.html

Busse WW, Brazinsky S, Jacobson K, Stricker W, Schmitt K, Vanden Burgt J, Donnell D, Hannon S, Colice GL. Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. J Allergy Clin Immunol. 1999 Dec;104(6):1215-22. — View Citation

Davies RJ, Stampone P, O'Connor BJ. Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol provides equivalent asthma control to chlorofluorocarbon beclomethasone dipropionate at approximately half the total daily dose. Respir Med. 1998 Jun;92 Suppl A:23-31. — View Citation

Gross G, Thompson PJ, Chervinsky P, Vanden Burgt J. Hydrofluoroalkane-134a beclomethasone dipropionate, 400 microg, is as effective as chlorofluorocarbon beclomethasone dipropionate, 800 microg, for the treatment of moderate asthma. Chest. 1999 Feb;115(2):343-51. — View Citation

Herland K, Akselsen JP, Skjønsberg OH, Bjermer L. How representative are clinical study patients with asthma or COPD for a larger "real life" population of patients with obstructive lung disease? Respir Med. 2005 Jan;99(1):11-9. — View Citation

IBM SPSS Statistics. 2010. Statistics family. Available online at: www.spss.com/uk/software/statistics/

Leach CL, Davidson PJ, Boudreau RJ. Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. Eur Respir J. 1998 Dec;12(6):1346-53. — View Citation

Leach CL, Davidson PJ, Hasselquist BE, Boudreau RJ. Influence of particle size and patient dosing technique on lung deposition of HFA-beclomethasone from a metered dose inhaler. J Aerosol Med. 2005 Winter;18(4):379-85. — View Citation

Travers J, Marsh S, Caldwell B, Williams M, Aldington S, Weatherall M, Shirtcliffe P, Beasley R. External validity of randomized controlled trials in COPD. Respir Med. 2007 Jun;101(6):1313-20. Epub 2006 Nov 17. — View Citation

Vanden Burgt JA, Busse WW, Martin RJ, Szefler SJ, Donnell D. Efficacy and safety overview of a new inhaled corticosteroid, QVAR (hydrofluoroalkane-beclomethasone extrafine inhalation aerosol), in asthma. J Allergy Clin Immunol. 2000 Dec;106(6):1209-26. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Severe asthma exacerbation (ATS/ERS based defn)	Exacerbation defined as: (i) Respiratory-related: Hospital attendance / admissions OR; A&E attendance OR (ii) Use of acute oral steroids**	1 year	No
Primary	Primary composite asthma control	Where control is defined as absence of: (i) Respiratory-related: Hospital attendance or admission; A&E attendance, OR; Out of hours attendance, OR; Out-patient department attendance (ii) GP consultations for lower respiratory tract infection (iii) Prescriptions for acute courses of oral steroids	1 year	No
Secondary	Exacerbation definition based on clinical experience	Defined as: (i) Respiratory-related: Hospital attendance / admissions OR; A&E attendance OR; Out of hours consultation OR; GP consultation OR (ii) Use of acute oral steroids	1 year	No
Secondary	Asthma control + SABA usage	Where control requires the absence of: (i) Respiratory-related: Hospital attendance or admission; A&E attendance, OR; Out of hours consultation, OR; Out-patient department attendance (ii) GP consultations for lower respiratory tract infection (iii) Prescriptions for acute courses of oral steroids (iv) Average daily prescribed dose of =200mcg salubtamol / =500mcg terbutaline	1 year	No
Secondary	Treatment success	(i) Control; a. No respiratory-related: i. Hospital attendance or admission ii. A&E attendance, OR iii. Out of hours consultation, OR iv. Out-patient department attendance b. No GP consultations for lower respiratory tract infection (ii) No prescriptions for acute courses of oral steroids (iii) No additional or change in therapy; Increased dose of ICS (=50% increase), and/or; Change in ICS and/or; Change in delivery device, and/or; Use of additional therapy as defined by: LABA, theophylline, leukotreine receptor antagonists (LTRAs).	1 year	No
Secondary	Asthma-related hospitalisations	Defined as sum of: (i) Definite: Hospitalisations coded with an asthma read code (ii) Definite + Probable: Hospitalisations with an asthma read code + uncoded hospitalisations occurring within a 7-day window (either side of the hospitalisation date) of an asthma read code	1 year	No
Secondary	Respiratory hospitalisations	Defined as the sum of: (i) Definite: Hospitalisations coded with a lower respiratory code (ii) Definite + Probable: Hospitalisations with an asthma read code + uncoded hospitalisations occurring within a 7-day window (either side of the hospitalisation date) of a lower respiratory read code	1 year	No
Secondary	SABA usage	Average daily dosage during outcome year - outcome SABA usage will be categorised within ranges used to match baseline SABA use to optimise matching of the treatment arms.	1 year	No
Secondary	ICS compliance	Based on prescription refills	1 year	No
Secondary	Oral Thrush	Defined as: (i) Topical oral anti-fungal prescriptions, and / or (ii) Coded for oral candidiasis	1 year	No