Clinical trial NCT01313585: Device Mixing in Asthma, a General Practice Research Database Study
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Keywords: Primary care
asthma management
inhaler device
maintenance therapy
reliever therapy
Easibreathe salbutamol
Lead sponsor: Research in Real-Life Ltd
Sponsor class: NETWORK
Collaborators: name: Teva Branded Pharmaceutical Products R&D, Inc.
First posted: 2011-03-14
Enrollment: 815377
Sex: ALL
Minimum age (years): 4
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Asthma patients on SABA therapy (any available) monotherapy who, at the index date, either:

(i) IPDI: initiate ICS therapy as BDP EB at the index date and also receive reliever therapy as either\*:

* Salbutamol EB, or
* Salbutamol MDI, OR, who (ii) IPDA: receive a recorded increase in ICS therapy as BDP EB at the index date and also receive reliever therapy as either\*:
* Salbutamol EB, or
* Salbutamol MDI.

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Proxy asthma control
timeFrame: One-year outcome period
measure: Total number of asthma exacerbations and exacerbation rate ratio
timeFrame: One-year outcome period
Secondary outcomes:
measure: Treatment success 1
timeFrame: One-year outcome period
measure: Treatment success 2 (independent of possible cost savings)
timeFrame: One-year outcome period
measure: Respiratory-related hospitalisations and referrals.
timeFrame: One-year outcome period
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: General Practice Research Database
Study officials:
affiliation: Company Director
name: David Price, Prof. MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Project Director
name: Alison Chisholm, MSc
role: STUDY_DIRECTOR
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