Real-world Effectiveness of Combination Therapy in Asthma

This study has been completed.
Sponsor:
Collaborator:
Mundipharma Research Limited
Information provided by:
Research in Real-Life Ltd
ClinicalTrials.gov Identifier:
NCT01141465
First received: June 9, 2010
Last updated: NA
Last verified: June 2010
History: No changes posted
  Purpose

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.


Condition Intervention
Asthma
Drug: Fluticasone / formoterol metered dose inhaler
Drug: Fluticasone / salmeterol dry powder inhaler
Drug: Budesonide / formoterol dry powder inhaler
Drug: Fluticasone / salmeterol metred dose inhaler
Drug: BUD/FOR dry powder inhaler

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Research in Real-Life Ltd:

Primary Outcome Measures:
  • Composite proxy for asthma control [ Time Frame: One-year outcome period ] [ Designated as safety issue: No ]
    • 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.

  • Exacerbations (total and rate ratio) [ Time Frame: One-year outcome period ] [ Designated as safety issue: No ]
    • Unscheduled hospital admissions / A&E attendance for asthma, AND/OR
    • Use of oral steroids.

  • 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) ] [ Designated as safety issue: No ]
    • No day-time symptoms;
    • No night-time symptoms;
    • No exacerbations;
    • No treatment-related adverse events
    • PEF ≥80% predicted = "normal"
    • No SABA use

  • GOAL exacerbations [ Time Frame: One year ] [ Designated as safety issue: No ]

    Absence of:

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


Secondary Outcome Measures:
  • Compliance with ICS/LABA combination therapy [ Time Frame: One year outcome period ] [ Designated as safety issue: No ]
    Percentage compliance calculated based on prescription refills

  • Compliance with ICS as part of ICS/LABA combination therapy [ Time Frame: One-year outcome period ] [ Designated as safety issue: No ]
    Percentage compliance calculated based on prescription refill

  • Treatment success [ Time Frame: One-year outcome period ] [ Designated as safety issue: No ]

    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).

  • SABA dosage [ Time Frame: One-year outcome period ] [ Designated as safety issue: No ]
    Categorised average SABA dosage during outcome year: 0mcg, >0-100mcg, >100-200mcg, >200-400mcg, >400-800mcg, >800mcg.


Enrollment: 815377
Study Start Date: January 2001
Study Completion Date: February 2010
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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 ≥twice BDP-equivalent dose as baseline ICS
Other Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Symbicort DPI

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.

  Eligibility

Ages Eligible for Study:   4 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01141465

Locations
United Kingdom
General Practice Research Database
London, United Kingdom, SW8 5NQ
Sponsors and Collaborators
Research in Real-Life Ltd
Mundipharma Research Limited
Investigators
Principal Investigator: David Price, Prof. MD Company Director
Study Director: Alison Chisholm, MSc Research Project Director
  More Information

Additional Information:
Publications:
Responsible Party: Professor David Price, Research in Real Life Limited
ClinicalTrials.gov Identifier: NCT01141465     History of Changes
Other Study ID Numbers: BS30
Study First Received: June 9, 2010
Last Updated: June 9, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Research in Real-Life Ltd:
Primary care
Asthma management
Combined therapy
Real-world
Effectiveness
Control
Exacerbations

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Budesonide
Formoterol
Salmeterol
Albuterol
Fluticasone
Fluticasone, salmeterol drug combination
Symbicort
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists

ClinicalTrials.gov processed this record on July 24, 2014