Device Mixing in Asthma, 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 Easi-breathe® (EB) - beclometasone dipropionate (BDP) breath-actuated inhaler (BAI) - and as-needed (prn) reliever medication (short-acting beta2-agonist [SABA] therapy) via either a BAI (i.e. Easi-breathe® [EB] salbutamol) or via a pressurised metered dose inhaler (MDI) (e.g. MDI salbutamol).

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. Inhalation therapy is the cornerstone of asthma treatment, used for the delivery of 'reliever' bronchodilator therapy (e.g. salbutamol) as well as anti-inflammatory corticosteroid 'maintenance' or 'controller' therapy. Currently available inhaler devices include MDIs, breath-actuated MDIs (BAIs), and dry powder inhalers (DPIs). Both BAIs and DPIs are actuated by the patient's inhalation manoeuvre, while MDIs are actuated by the patient's pressing of a button, which must thus be coordinated with inhalation. The clinical effectiveness of inhalation therapy derives from delivery of drug to the target sites in the lungs, and evidence is mounting that suboptimal use of inhaler devices is a common problem contributing to compromised asthma control for many patients. Indeed, decreased asthma control has been linked to the number of mistakes when using MDIs for delivering inhaled corticosteroids (ICS). There is also evidence that the ability of patients to use the different inhaler device types is variable. Nonetheless, recent reviews of RCTs, while recognising the importance of inhaler technique, have concluded that inhaler devices do not differ significantly in efficacy and that the cheapest inhaler device should be used. However, as results are based on RCTs they should be applied with care in light of the aforementioned issues around external validity of RCTs and the ability to extrapolate their findings across a broad patient population. Moreover, patients enrolled in RCTs typically receive extensive training and must demonstrate and maintain proper inhaler technique, seldom accomplished in a real-world setting. The aim of this study is to compare the absolute and relative effectiveness of ICS (maintenance) plus SABA (reliever) therapy delivered via same-type devices (namely BDP via EB plus salbutamol via EB [BAI]) and that delivered via different device types (i.e. BDP via EB [BAI] plus SABA via MDI) in a real-life, representative, UK primary care asthma population.

Official Title
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Retrospective, Real-life Observational Evaluation of the Effectiveness of Mixed Maintenance and Reliever Inhaler Types in Patients in the Management of Asthma in a Representative UK Primary Care Population

Conditions
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Asthma

Intervention / Treatment
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* Drug: Initiation of beclometasone via the Easibreathe device plus salbutamol via the Easibreathe device
* Drug: Initiation of beclometasone via the Easibreathe device plus salbutamol via and MDI device
* Drug: Increase of beclometasone via the Easibreathe device plus salbutamol via the Easibreathe device
* Drug: Increase of beclometasone via the Easibreathe device plus salbutamol via an MDI


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: a diagnostic code for asthma, and / or ≥2 prescriptions for asthma at different points in time during the prior year and/ or ≥2 prescriptions for asthma therapies during the outcome year, including ≥1 ICS prescription (in addition to that received at IPD) - IPDI cohort only Be on current asthma therapy (for the IPDA cohort only): ≥1 ICS prescription in the prior year, and ≥1 other asthma prescription during the baseline year. 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 received a combination inhaler in addition to a separate ICS inhaler in the baseline year; and/or received a long-acting beta2-agonsist (LABA) in addition to a separate ICS inhaler in the baseline year received ICS therapy during baseline year via DPI (in IPDA cohort only).

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 |
| --- | --- |
| IPDA salbutamol MDI<br>receive a recorded increase in ICS therapy as BDP Easibreathe at the index date and also receive salbutamol MDI | Drug: Increase of beclometasone via the Easibreathe device plus salbutamol via an MDI<br> <br> |
| IPDA salbutamol EB<br>receive a recorded increase in ICS therapy as BDP Easibreathe at the index date and also receive salbutamol Easibreathe | Drug: Increase of beclometasone via the Easibreathe device plus salbutamol via the Easibreathe device<br> <br> |
| IPDI salbutamol EB<br>initiate ICS therapy as BDP Easibreathe at the index date and also receive salbutamol Easibreathe | Drug: Initiation of beclometasone via the Easibreathe device plus salbutamol via the Easibreathe device<br> <br> |
| IPDI salbutamol MDI<br>initiate ICS therapy as BDP Easibreathe at the index date and also receive salbutamol MDI | Drug: Initiation of beclometasone via the Easibreathe device plus salbutamol via and MDI device<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proxy asthma control | Control defined as: No recorded hospital attendance for asthma, including admission, Accident & Emergency (A&E) attendance, out-of-hours attendance, or Out-Patient Department (OPD) attendance, AND No prescriptions for oral steroids, AND No GP consultations, hospital admissions or A&E attendance for lower respiratory tract infections (LRTI) requiring antibiotics. | One-year outcome period | 
| Total number of asthma exacerbations and exacerbation rate ratio | Where exacerbation is defined as an occurrence of: Unscheduled hospital admissions / A&E attendance for asthma, OR Use of oral steroids | One-year outcome period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success 1 | Success: defined as: (i) Exacerbation: Unscheduled hospital admissions / A&E attendance for asthma, OR Acute use of oral steroids AND (ii) No consultations, hospital admissions or A&E attendance for lower respiratory tract infections (LRTI) requiring antibiotics AND (iii) No change in therapeutic regimen: Increased dose of ICS, and/or Change in ICS/LABA, and/or Change in delivery device, and/or Use of additional therapy as defined by: theophylline, leukotreine receptor antagonists (LTRAs). | One-year outcome period | 
| Treatment success 2 (independent of possible cost savings) | Success: defined as: (i) Exacerbation: Unscheduled hospital admissions / A&E attendance for asthma, OR Acute use of oral steroids AND (ii) No consultations, hospital admissions or A&E attendance for lower respiratory tract infections (LRTI) requiring antibiotics AND (iii) No change in therapeutic regimen: Increased dose of ICS, and/or Use of additional therapy as defined by: theophylline, leukotreine receptor antagonists (LTRAs). | One-year outcome period | 
| Respiratory-related hospitalisations and referrals. | Mean number of respiratory-related hospitalisations and referrals per patient recorded during the one-year outcome period | One-year outcome period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary care, asthma management, inhaler device, maintenance therapy, reliever therapy, Easibreathe salbutamol