Qvar Versus Clenil, a General Practice Research Database Study

Completed

• Conditions: Asthma
• Interventions: Drug: extra fine particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler; Drug: standard particle particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler

• Registration Number: NCT01400217
• Lead Sponsor: Research in Real-Life Ltd

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 1991-01
• Primary Completion: 2010-10
• Study Completion: 2010-10
• Study First Submitted: 2011-07-20
• Study First Submitted QC: 2011-07-21
• Study First Posted: 2011-07-22
• Status Verified: 2012-10
• Last Update Submitted: 2012-10-29
• Last Update Posted: 2012-10-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56985

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

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
IPDI EF HFA-BDP	extra fine particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler	Patients initiating inhaled corticosteroid therapy as extra-fine HFA-BDP MDI at the index date
IPDI SP HFA-BDP	standard particle particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler	Patients initiating inhaled corticosteroid therapy as standard particle HFA-BDP MDI at the index date
IPDA SP HFA-BDP	standard particle particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler	Patients increased inhaled corticosteroid therapy as standard particle HFA-BDP MDI at the index date
IPDA EF HFA-BDP	extra fine particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler	Patients increased inhaled corticosteroid therapy as extra fine particle HFA-BDP MDI at the index date
IPDS SP HFA-BDP	standard particle particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler	Patients increased inhaled corticosteroid therapy as standard particle HFA-BDP MDI at the index date
IPDS EF HFA-BDP	extra fine particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler	Patients increased inhaled corticosteroid therapy as extrafine particle HFA-BDP MDI at the index date

Primary Outcome Measures

Name	Time	Method
Severe asthma exacerbation (ATS/ERS based defn)	1 year	Exacerbation defined as: (i) Respiratory-related: 1. Hospital attendance / admissions OR; 2. A\&E attendance OR (ii) Use of acute oral steroids\*\*
Primary composite asthma control	1 year	Where control is defined as absence of: (i) Respiratory-related: 1. Hospital attendance or admission; 2. A\&E attendance, OR; 3. Out of hours attendance, OR; 4. Out-patient department attendance (ii) GP consultations for lower respiratory tract infection (iii) Prescriptions for acute courses of oral steroids

Secondary Outcome Measures

Name	Time	Method
Exacerbation definition based on clinical experience	1 year	Defined as: (i) Respiratory-related: 1. Hospital attendance / admissions OR; 2. A\&E attendance OR; 3. Out of hours consultation OR; 4. GP consultation OR (ii) Use of acute oral steroids
Asthma control + SABA usage	1 year	Where control requires the absence of: (i) Respiratory-related: 1. Hospital attendance or admission; 2. A\&E attendance, OR; 3. Out of hours consultation, OR; 4. 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
Treatment success	1 year	(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; 1. Increased dose of ICS (≥50% increase), and/or; 2. Change in ICS and/or; 3. Change in delivery device, and/or; 4. Use of additional therapy as defined by: LABA, theophylline, leukotreine receptor antagonists (LTRAs).
Asthma-related hospitalisations	1 year	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
Respiratory hospitalisations	1 year	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
SABA usage	1 year	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.
ICS compliance	1 year	Based on prescription refills
Oral Thrush	1 year	Defined as: (i) Topical oral anti-fungal prescriptions, and / or (ii) Coded for oral candidiasis

Trial Locations

Locations (1)

Research in Real Life Ltd; 🇬🇧 Cawston, Norfolk, United Kingdom