Real-world Effectiveness of Combination Therapy in Asthma

June 9, 2010 updated by: Research in Real-Life Ltd

A Retrospective Evaluation of the Effectiveness of Fixed-dose Combination Inhaled Corticosteroid /. Long-acting Beta Agonist (ICS/LABA) Therapy in the Management of Asthma in a Representative UK Primary Care Population

This study will evaluate and compare the effectiveness of asthma management in patients with evidence of persistent asthma following a switch in asthma therapy to combination inhaled glucocorticosteroid (ICS) / long-acting bronchodilator (LABA) therapy as either: fixed-combination fluticasone propionate / salmeterol (FP/SAL; Seretide®) via pressurised metered-dose inhaler (pMDI) or dry-powder inhaler (DPI) plus as-needed (prn) reliever therapy (salbutamol as DPI, BAI or pMDI), or fixed-combination budesonide / formoterol (BUD/FOR; Symbicort®) via DPI plus prn reliever therapy (salbutamol as DPI, BAI or pMDI or bricanyl as DPI). The final analysis plan will define exact comparators and age groups to be studied after reviewing baseline data.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

The fixed combination asthma inhalers FP/SAL (as pMDI and DPI) and BUD/FOR (as DPI) are indicated for use in asthma when adequate asthma control is not achieved with low / medium dose ICS therapy and prn reliever therapy (a short-acting beta-agonist [SABA]). Fixed combination inhalers are also indicated in patients already adequately controlled on separate ICS/LABA therapy. However, emerging trends in asthma prescribing indicate increasing use of add-on therapies (particularly in the form of combination inhalers) in the early stages of asthma therapy, even as first-line therapy.

The British Thoracic Society (BTS) Scottish Intercollegiate Guidelines Network (SIGN) guidelines on the management of asthma advise that there is no difference in efficacy between ICS/LABA therapy given as separate or combined inhalers. However, they do note that, once a patients is on stable therapy, combination inhalers have the advantage of guaranteeing that patients do not take their LABA without their ICS.

In practice, there is significant pressure (supported by asthma guidelines) to use the least expensive, effective inhaled therapies available. While the effect of increased use of combination therapies in terms of patient benefits remains uncertain, the impact on treatment costs for the United Kingdom's (UK's) National Health Service (NHS) is unequivocal and, to date, there are limited data available as to the absolute and relative effectiveness of the ICS/LABA combination therapies currently licensed.

There are a number of inhaler delivery devices available for use in asthma management. Whatever therapy is prescribed, optimal treatment response requires effective drug delivery within the airways; selecting the most appropriate delivery device for an asthma patient, therefore, plays an important role in optimising their asthma control. According to the recent BTS/SIGN guidelines, there is currently no evidence of a clinical difference in the effectiveness of therapy delivery via pMDI ± spacer compared with DPI in either adults or children, and more recent DPIs are rated as effective as older DPIs. Effective use of DPIs and pMDI requires entirely different inhalation techniques and there is some debate as to whether patients prescribed different device types for their reliever and preventer medication (requiring different techniques for each) may have poorer disease control than those prescribed the same device type for both preventer and reliever. Combining aerosols (e.g. pMDI preventer plus BAI reliever) is not considered to cause a problem in this respect.

The aim of this study is to compare the absolute and relative effectiveness of currently licensed ICS/LABA combinations - FP/SAL and BUD/FOR (and their available delivery devices) - in children and adults with asthma whose therapy was changed or increased. Consideration will also be given to the effect of reliever therapy inhaler and the effect of consistency of device used (i.e. same or different devices for preventer and inhaler therapies) on asthma control outcomes. Also to be evaluated are the associated impact of inhaler technique review, recorded inhaler handling problems and use of a spacer in conjunction with a pMDI in terms of achieving asthma control outcomes.

Study Type

Observational

Enrollment (Actual)

815377

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SW8 5NQ
        • General Practice Research Database

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 80 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Primary care asthma patients receiving ICS therapy (any of BDP, extrafine HFA-BDP, BUD or FP as pMDI, BAI or DPI) plus as needed SABA reliever therapy who underwent a change in asthma therapy to combination ICS/LABA therapy as FP/SAL (MDI or DPI) or BUD/FOR (DPI) at the same or at least twice the BDP-equivalent dose of ICS prescribed during baseline.

Description

Inclusion Criteria:

  • Aged: 4-80 years: Paediatric cohort (aged 4-11 years); Adult cohort (aged 12-69 years); Elderly cohort (aged 70-80 years.
  • Evidence of asthma: i.e. a diagnostic code of asthma or ≥2 prescriptions for asthma at different points in time during the prior year, including one ICS prescription.
  • Be on current asthma therapy: i.e. ≥1 asthma prescriptions in the prior year, and at least 1 other asthma prescription during the same period.
  • 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:

  • Diagnostic read code for chronic respiratory disease (including COPD) at any time
  • On maintenance oral steroid therapy at baseline
  • Any patients receiving a combination inhaler in addition to their separate ICS inhaler in the baseline year.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
IPDA FP/SAL DPI
Patients who were on inhaled corticosteroid therapy during the baseline year (any ICS therapy) who, at an index prescription date, initiated combination therapy as FP/SAL DPI at ≥twice the equivalent BDP-equivalent dose
Drug: Fluticasone / salmeterol dry powder inhaler
Prescribed at the same BDP-equivalent dose as baseline ICS
Other Names:
  • Seretide DPI
Drug: Fluticasone / salmeterol dry powder inhaler
Prescribed at ≥twice BDP-equivalent dose as baseline ICS
Other Names:
  • Seretide DPI
IPDA FP/SAL MDI
Patients who were on inhaled corticosteroid therapy during the baseline year (any ICS therapy) who, at an index prescription date, initiated combination therapy as FP/SAL MDI at ≥twice the equivalent BDP-equivalent dose
Drug: Fluticasone / salmeterol metred dose inhaler
Prescribed at ≥twice BDP-equivalent dose as baseline ICS
Other Names:
  • Seretide MDI
IPDI FP/SAL DPI
Patients who were on inhaled corticosteroid therapy during the baseline year (any ICS therapy) who, at an index prescription date, initiated combination therapy as FP/SAL DPI at equivalent BDP-equivalent dose
Drug: Fluticasone / salmeterol dry powder inhaler
Prescribed at the same BDP-equivalent dose as baseline ICS
Other Names:
  • Seretide DPI
Drug: Fluticasone / salmeterol dry powder inhaler
Prescribed at ≥twice BDP-equivalent dose as baseline ICS
Other Names:
  • Seretide DPI
IPDI BUD/FOR DPI
Patients who were on inhaled corticosteroid therapy during the baseline year (any ICS therapy) who, at an index prescription date, initiated combination therapy as BUD/FOR DPI at equivalent BDP-equivalent dose
Drug: Budesonide / formoterol dry powder inhaler
Prescribed at the same BDP-equivalent dose as baseline ICS
Other Names:
  • Symbicort DPI
IPDI FP/SAL MDI
Patients who were on inhaled corticosteroid therapy during the baseline year (any ICS therapy) who, at an index prescription date, initiated combination therapy as FP/SAL MDI at equivalent BDP-equivalent dose
Drug: Fluticasone / formoterol metered dose inhaler
Prescribed at the same BDP-equivalent dose as baseline ICS
Other Names:
  • Seretide MDI
IPDA BUD/FOR DPI
Patients who were on inhaled corticosteroid therapy during the baseline year (any ICS therapy) who, at an index prescription date, initiated combination therapy as BUD/FOR DPI at ≥twice the equivalent BDP-equivalent dose
Drug: BUD/FOR dry powder inhaler
Prescribed at ≥twice BDP-equivalent dose as baseline ICS
Other Names:
  • Symbicort DPI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite proxy for asthma control
Time Frame: One-year outcome period
  • 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
Exacerbations (total and rate ratio)
Time Frame: One-year outcome period
  • Unscheduled hospital admissions / A&E attendance for asthma, AND/OR
  • Use of oral steroids.
One-year outcome period
GOAL Total Control (proxy measure to replicate total control as measured in the GOAL RCT in a real world patient population
Time Frame: 6 months (sensitivity analysis at 8 weeks)
  • No day-time symptoms;
  • No night-time symptoms;
  • No exacerbations;
  • No treatment-related adverse events
  • PEF ≥80% predicted = "normal"
  • No SABA use
6 months (sensitivity analysis at 8 weeks)
GOAL exacerbations
Time Frame: One year

Absence of:

  • Documented episodes of hospitalisations AND/OR
  • Exacerbation treatment - oral steroids or antibiotics for asthma over one year
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compliance with ICS/LABA combination therapy
Time Frame: One year outcome period
Percentage compliance calculated based on prescription refills
One year outcome period
Compliance with ICS as part of ICS/LABA combination therapy
Time Frame: One-year outcome period
Percentage compliance calculated based on prescription refill
One-year outcome period
Treatment success
Time Frame: One-year outcome period

Success of the therapeutic regimen, defined as the absence of:

  • Exacerbation, and
  • Increased dose of ICS, and
  • Change in ICS/LABA, and
  • Change in delivery device, and
  • Use of additional therapy as defined by: oral steroids, theophylline, leukotreine receptor antagonists (LTRAs).
One-year outcome period
SABA dosage
Time Frame: One-year outcome period
Categorised average SABA dosage during outcome year: 0mcg, >0-100mcg, >100-200mcg, >200-400mcg, >400-800mcg, >800mcg.
One-year outcome period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Research in Real-Life Ltd

Collaborators

Mundipharma Research Limited

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2001

Primary Completion (ACTUAL)

June 1, 2007

Study Completion (ACTUAL)

February 1, 2010

Study Registration Dates

First Submitted

June 9, 2010

First Submitted That Met QC Criteria

June 9, 2010

First Posted (ESTIMATE)

June 10, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

June 10, 2010

Last Update Submitted That Met QC Criteria

June 9, 2010

Last Verified

June 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BS30

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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