Condition category
Respiratory
Date applied
13/08/2014
Date assigned
20/08/2014
Last edited
13/11/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
About a million people in the UK are diagnosed with the lung condition known as chronic obstructive pulmonary disease (COPD) where they develop progressive breathlessness, phlegm and cough. People with COPD often experience sudden worsening of symptoms, known as acute exacerbations of COPD (AECOPD). Over 70% of patients who see their general practitioner (GP) with AECOPD are prescribed an antibiotic. However, many of these patients may not actually benefit from these antibiotics because antibiotics only work against bacteria, and many AECOPD are triggered by other causes including viral infections, and environmental factors such as common pollutants or the weather. Antibiotics also increase the risk of side effects in patients. Taking frequent antibiotics can cause bacteria in the lungs and elsewhere to become resistant to antibiotics and may make future infections including AECOPDs harder to treat. Antibiotic resistant bacteria are also a very significant threat to society as a whole. Currently GPs decide to prescribe antibiotics for AECOPD based on patient’s symptoms, and it is difficult for GPs to predict which patients could safely be managed without antibiotics. It is possible to help GPs to know which patients may not need antibiotic for their AECOPD by doing a simple test. C-reactive protein (CRP) is a protein found in blood which can be measured quickly and easily using a point-of-care test (POCT). This test requires a small finger prick blood sample and the results are obtained within 5 minutes. When CRP levels are low, patients with AECOPD are unlikely to benefit from antibiotics. In the PACE study half of the participants with AECOPD will have a CRP test done in addition to receiving their usual GP care and the other half of participants will be managed by their usual GP care only. The PACE study will determine whether use of the simple, rapid CRP-POCT in addition to clinical assessment of the patient leads to improved antibiotic prescribing in AECOPD.

Who can participate?
Adults over the age of 40 with a diagnosis of chronic obstructive pulmonary disease (COPD) can be included in the study when they present to one of the participating primary care practices with an acute exacerbation of COPD that has lasted for at least 24 hours but equal to or less than 21 days.

What does the study involve?
Participants are first examined by their GP according to their usual clinical practice. The GP or a nurse then take more information about the patient and record this. This will include things like whether they smoke, what medications are they currently taking and temperature. A quality of life questionnaire (EQ5D) and respiratory questionnaire (CRQSAS) are also completed and participants are asked to provide a throat swab or sputum sample for research purposes. Participants are then randomly allocated to one of the two groups (study arms) of the study. One group is treated in the usual way according to the best current practice. The other group receives the best current practice plus have an additional finger prick CRP blood test to help the GP to decide if an antibiotic should be prescribed. The participants in the CRP test arm then have a CRP test done every time they see their GP for AECOPD for the next four weeks. All participants are followed up using telephone calls once a week for the next two weeks. At week four, all participants return to their GP practice for a face-to-face assessment. This will include completing a further quality of life and chronic respiratory questionnaire and answering questions about things like adverse events, medication and resource use. All participants are then asked to provide another throat swab or sputum sample.

What are the possible benefits and risks of participating?
There are a number of potential benefits to participants as listed below:
1. Avoiding unnecessary antibiotics and therefore any adverse effects from taking them
2. Using antibiotics appropriately when they are likely to be beneficial
3. Closer monitoring and follow-up by the GP regarding the illness
4. Developing awareness around prudent use of antibiotics for AECPOD and in general for the patients and GPs
5. The GPs will have their knowledge on current best management of COPD reinforced which will benefit their patients.
Potential risk:
GPs may withhold antibiotic treatment in participants with a low CRP value. However, all GPs are trained in the current best management of AECOPD. The GPs would be free to use antibiotics if they think this to be appropriate regardless of CRP values. Many cases of acute exacerbations are routinely treated without antibiotics at the moment, especially when the GP feels that the exacerbation is not likely to be caused by bacterial agents. The CRP test would help in making better decisions about antibiotic prescriptions.

Where is the study run from?
GP practices in Wales, Thames Valley and South London (UK).

When is the study starting and how long is it expected to run for?
Recruitment of participants for the study starts in November 2014. The first winter period will comprise an internal pilot stage which will be carried out in 10 GP practices in Wales. During the second winter period, at least 60 GP practices (approximately 20 in each of the three regions: Wales, Thames Valley and South London) will be taking part.

Who is funding the project?
The National Institute of Health Research (NIHR) Health Technology Assessment (HTA) programme

Who is the main contact?
Professor Chris Butler
christopher.butler@phc.ox.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Chris Butler

ORCID ID

Contact details

Nuffield Department of Primary Care Health Sciences
University of Oxford
Radcliffe Observatory Quarter
Woodstock Road
Oxford
OX2 6GG
United Kingdom
+44 (0)1865 289363
christopher.butler@phc.ox.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

SPON 1189-12; HTA 12/33/12

Study information

Scientific title

Primary care use of a C-Reactive Protein (CRP) Point of Care Test (POCT) to help target antibiotic prescribing to patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) who are most likely to benefit: Two-arm individually randomised controlled trial.

Acronym

PACE

Study hypothesis

Using a C- Reactive Protein (CRP) point of care test (POCT) in addition to current best clinical practice in managing acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) will reduce antibiotic consumption without negatively affecting patient recovery as compared to current best clinical practice alone.#

More details can be found at http://www.nets.nihr.ac.uk/projects/hta/123312

Ethics approval

Wales REC 6, 15/09/2014, REC ref: 14/WA/1106

Study design

Two-arm individually randomised controlled trial.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

Not available in web format. Please use contact details provided to request a patient information material

Condition

Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)

Intervention

PACE will assess use of a C-reactive protein (CRP) point-of-care test (POCT) to guide antibiotic treatment decisions for patients presenting in primary care with AECOPD. Participants will be allocated to a usual clinical care or an intervention arm. Patients randomised to the intervention arm will have a CRP test at every consultation for AECOPD that occurs in the four weeks following randomisation. Control patients will not have a CRP test (as part of this study) at any time during their participation.

The CRP POCT is developed by Alere. The test requires 1.5ìl of capillary blood (finger prick sample) and takes less than 4 minutes to provide a quantitative result.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

This study is based on two co-primary outcomes:
1. Antibiotic consumption at any point during the four weeks post-randomisation, measured using telephone interviews at one-week and two-weeks and face-to-face interview at four-weeks
2. Patient-reported health-related quality of life (HRQoL) measured by the Chronic Respiratory Questionnaire Self-Administered Standardised (CRQ-SAS) via telephone interview at two-weeks

Secondary outcome measures

1. Prevalence of significant antibiotic resistant organisms (including Streptococcus spp., H. influenzae and parainfluenzae and Enterobacteriaceae) cultured from sputum or throat swab at 4 weeks
2. Disease-specific health-related quality of life over time measured using CRQ-SAS (measured at weeks 1, 2 and 4)
3. Health utility measured using the EuroQol-5D (EQ-5D) (measured at weeks 1, 2 and 4)
4. Antibiotic prescribing at the index consultation
5. Use of other COPD treatments including oral steroids (measured at weeks 1, 2 and 4)
6. Adverse effects potentially attributable to antibiotics prescribed for their exacerbation (nausea, vomiting, diarrhoea, thrush, and rash) (measured at weeks 1, 2 and 4)
7. Primary and secondary care consultations, including hospitalisations (measured at month 6)
8. Costs (total NHS cost) and cost-effectiveness (measured at month 6)
9. Incidence of pneumonia (measured by patient and GP report at week 4 and month 6)

Overall trial start date

01/11/2014

Overall trial end date

31/07/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adults aged 40
2. Spirometry confirmed (at any time point prior to admission) COPD (post bronchodilator FEV1/FVC < 0.7)
3. Patients with mild, moderate and severe disease: that is FEV1 of more than 30% of the predicted value as indicated by the age and the height of the person (GOLD stage 1-3)
4. Have a current AECOPD, defined as, “an event in the natural course of the disease characterized by a change in the patient's baseline dyspnoea, cough and/or sputum that is beyond normal day-to-day variations, is acute in onset and may warrant a change in regular medication”
5. The exacerbation has lasted for at least 24 hours but equal to or less than 21 days
6. Are able to attend the GP surgery
7. Are able to provide informed consent and complete study procedures.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

650

Participant exclusion criteria

1. Very severe COPD (GOLD stage 4; FEV1 < 30% predicted)
2. Coexisting infection (i.e. urinary tract infection, cellulitis)
3. Suspected pneumonia or requiring immediate hospital admission
4. History of requiring mechanical ventilation for an AECOPD
5. Active chronic inflammatory condition (i.e. rheumatoid arthritis)
6. Currently already taking high dose oral steroids (equivalent to 60mg per day or more of prednisolone)
7. Has taken oral antibiotics in previous four weeks
8. Life limiting malignancy
9. Cystic fibrosis
10. Current tracheotomy
11. Bronchiectasis of any aetiology other than COPD
12. Previously been recruited into the PACE study.

Recruitment start date

01/11/2014

Recruitment end date

31/07/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Nuffield Department of Primary Care Health Sciences
Oxford
OX2 6GG
United Kingdom

Sponsor information

Organisation

Cardiff University (UK)

Sponsor details

c/o Dr Kathy J Pittard-Davies
RIES
30-36 Newport Road
Cardiff
CF24 0DE
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK), ref: 12/33/12

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Publication citations

Additional files

Editorial Notes