Condition category
Respiratory
Date applied
28/05/2009
Date assigned
30/07/2009
Last edited
12/09/2012
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Christopher E Brightling

ORCID ID

Contact details

Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
ceb17@le.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

G0601369

Study information

Scientific title

The use of biomarkers to direct antibiotic and systemic corticosteroid therapy in chronic obstructive pulmonary disease (COPD) exacerbations: a randomised controlled study

Acronym

BEAT:COPD

Study hypothesis

Chronic obstructive pulmonary disease (COPD) is a common condition associated with significant morbidity and mortality. It is predicted to be the third leading cause of death worldwide by 2020. COPD exacerbations are an important feature of the disease, accounting for significant morbidity, mortality and health care costs.

COPD exacerbations are associated with bacterial and viral respiratory infections and airway inflammation. Current guidelines advocate the use of oral corticosteroids for patients with a COPD exacerbation who have increased dyspnoea and antibiotics in those with a history of more purulent sputum. A Cochrane review for the use of systemic corticosteroids and antibiotics in COPD exacerbations have shown that corticosteroids increase the rate of recovery following a severe exacerbation, reduce the length of hospital admission and reduce the proportion of patients that have treatment failure. However, it is likely these small corticosteroid-related benefits are confined to a sub-group of patients. Likewise antibiotic therapy in COPD exacerbations is beneficial, with a reduction in short-term mortality and treatment failure; however, the range of response was large and it is estimated that antibiotics are of clinical benefit in only 25 - 50% of COPD exacerbations.

Our inability to identify accurately which patients with a COPD exacerbation should receive antibiotics and or corticosteroids inevitably leading to inappropriate and excessive use of treatment, is the basis of our hypothesis and the use of a single or composite to deliver targeted antibiotic and or corticosteroid therapy at the time of a COPD exacerbation.

As of 20/10/2009 this record was updated after a change to the protocol following MHRA approval. All changes can be found under the relevant section with the above update date. Please note that at this time, the following changes were made:
1. The study design has been updated; the initial study design was: 'Randomised controlled study'
2. The target number of participants has changed; the initial target number of participants was: '136'
3. A placebo arm was added to the interventions section; details of this can be found in the interventions section.

Ethics approval

Leicestershire, Northamptonshire and Rutland Research Ethics Committee approved in September 2007 (ref: 07/H0406/157)

Study design

Amended 20/10/2009: A randomised biomarker-driven prednisolone/placebo intervention study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Chronic obstructive pulmonary disease (COPD)

Intervention

Current interventions as of 20/10/2009:
Randomised 12-month parallel group study with two study groups:
1. Standard care therapy group: subjects will receive treatment as decided by a physician and complying with the Global Initiative for Chronic Obstructive Lung Disease (GOLD)/National Institute for Health and Clinical Excellence (NICE) guidelines for management of COPD exacerbations. This may include increasing bronchodilators, a short duration of oral corticosteroids plus or minus antibiotic therapy (according to local hospital microbiological guidelines).
2. Biomarker directed therapy group: subjects will be assigned to 14 days of oral prednisolone or matching placebo as guided by the biomarker and/or 7 days (maximum) of antibiotic therapy.

Randomisation by minimisation: COPD severity, eosinophilic airway inflammation, exacerbation frequency from previous 12 months. Each arm of the study will be followed up for 12 months.

Initial interventions at time of registration:
Randomised 12-month parallel group study with two study groups:
1. Standard care therapy group: subjects will receive treatment as decided by a physician and complying with the Global Initiative for Chronic Obstructive Lung Disease (GOLD)/National Institute for Health and Clinical Excellence (NICE) guidelines for management of COPD exacerbations. This may include increasing bronchodilators, a short duration of oral corticosteroids plus or minus antibiotic therapy (according to local hospital microbiological guidelines).
2. Biomarker directed therapy group: subjects will be assigned to 14 days of oral prednisolone and/or 7 days (maximum) of antibiotic therapy or neither as guided by the biomarker.

Randomisation by minimisation: COPD severity, eosinophilic airway inflammation, exacerbation frequency from previous 12 months. Each arm of the study will be followed up for 12 months.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

1. Proportion of exacerbations treated with antibiotics and corticosteroids
2. Proportion of exacerbations that are associated with a treatment failure
3. Change in health status

Looked at within 3 months of the completion of the study.

Added 20/10/2009:
The study has 80% powering to show equivalence in a minimal change of health status (0.5: measured by the mCRQ).

Secondary outcome measures

1. Change in forced expiratory volume in one second (FEV1)
2. Markers of airway inflammation
3. Number of adverse reactions

Looked at within 3 months of the completion of the study.

Overall trial start date

01/09/2009

Overall trial end date

01/09/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Provision of informed consent
2. Male or female
3. Aged 40 years or over
4. Diagnosis of COPD
5. Greater than one exacerbation requiring antibiotics and or corticosteroids in the preceding year

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

106 (standard therapy arm: 53; biomarker arm: 53)

Participant exclusion criteria

1. Current active respiratory tuberculosis
2. Upon questioning the patient known human immunodeficiency virus (HIV) infection or positive hepatitis B or C
3. Known inability to produce a sputum sample during the induced sputum procedure
4. Clinically relevant disease or disorder (past or present) which in the opinion of the investigator may either put the subject at risk because of participating in the study or may influence the results of the study or the subject's ability to participate in the study
5. Any clinically relevant lung disease other than COPD
6. Donation of blood within 3 months or during the study (for other than study purpose)
7. Pregnancy or lactation

Recruitment start date

01/09/2009

Recruitment end date

01/09/2010

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Glenfield Hospital
Leicester
LE3 9QP
United Kingdom

Sponsor information

Organisation

University Hospitals of Leicester NHS Trust (UK)

Sponsor details

Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
carolyn.maloney@uhl-tr.nhs.uk

Sponsor type

Government

Website

http://www.uhl-tr.nhs.uk/

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK) (ref: G0601369)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22447964

Publication citations

  1. Results

    Bafadhel M, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE, Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial., Am. J. Respir. Crit. Care Med., 2012, 186, 1, 48-55, doi: 10.1164/rccm.201108-1553OC.

Additional files

Editorial Notes