Qvar Versus Clenil, a General Practice Research Database Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: extra fine particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler
* Drug: standard particle particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IPDI EF HFA-BDP<br>Patients initiating inhaled corticosteroid therapy as extra-fine HFA-BDP MDI at the index date | Drug: extra fine particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler<br>* 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<br>* Other names: Qvar;|
| IPDI SP HFA-BDP<br>Patients initiating inhaled corticosteroid therapy as standard particle HFA-BDP MDI at the index date | Drug: standard particle particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler<br>* 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<br>* Other names: Fostair;|
| IPDA SP HFA-BDP<br>Patients increased inhaled corticosteroid therapy as standard particle HFA-BDP MDI at the index date | Drug: standard particle particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler<br>* 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<br>* Other names: Fostair;|
| IPDA EF HFA-BDP<br>Patients increased inhaled corticosteroid therapy as extra fine particle HFA-BDP MDI at the index date | Drug: extra fine particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler<br>* 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<br>* Other names: Qvar;|
| IPDS SP HFA-BDP<br>Patients increased inhaled corticosteroid therapy as standard particle HFA-BDP MDI at the index date | Drug: standard particle particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler<br>* 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<br>* Other names: Fostair;|
| IPDS EF HFA-BDP<br>Patients increased inhaled corticosteroid therapy as extrafine particle HFA-BDP MDI at the index date | Drug: extra fine particle hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler<br>* 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<br>* Other names: Qvar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| ICS compliance | Based on prescription refills | 1 year | 
| Oral Thrush | Defined as: (i) Topical oral anti-fungal prescriptions, and / or (ii) Coded for oral candidiasis | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Care, Particle size, beclomethasone dipropionate, Asthma Management, Maintenance Therapy, Metered-Dose Inhaler