Title: Sputum colour charts to guide antibiotic self-treatment of acute exacerbation of COPD (Colour-COPD)
Funder: Department of Health and Social Care

Abstract: Chronic obstructive pulmonary disease (COPD) is a common lung problem mostly affecting adults over the age of 40. It causes breathlessness and cough, and patients often experience flare ups of their symptoms, known as exacerbations. These may be triggered by infection, and these can be caused by viruses or bacteria. Despite the fact that infections do not cause all flare ups it is common for patients to be given a ‘rescue pack’ which includes antibiotics and steroids for use when they have symptoms of a flare up. This means that antibiotics can be overused, which may mean that resistance is built up and the antibiotic may not work properly in future. It is therefore important to find ways we can safely reduce antibiotic use, but without causing harm to COPD patients. _x000D_ One way of recognising that the flare-up is caused by bacteria, is to look at the colour of sputum (phlegm) patients produce, and compare this to a colour chart. Antibiotics are only suggested if the colour indicates an infection. We think that appropriate use of a chart could reduce antibiotic use but without worsening the chance that patients will need to be admitted to hospital._x000D_ _x000D_ We will include 2954 COPD patients in our study who have had 2 or more flare-ups in the last year. Half of the patients will receive usual care (a self-management plan and rescue pack containing antibiotics and steroids) and half will receive this usual care plus a 5-colour sputum chart. Patients using the colour chart will be instructed only to use the antibiotic part of the rescue pack if their sputum is green, whilst those receiving usual care will be instructed to use both elements of their pack. We will recruit patients from approximately 80 general practices and will give out the colour charts and collect the data during usual consultations with the practice nurses or doctors. Patients will be followed up for 1 year, and the number of admissions to hospital compared between the 2 groups. We will also compare the rate of antibiotic prescription, number of GP consultations, rate of antibiotic related problems (such as thrush), amount of antibiotic resistance, quality of life, rate of exacerbations overall and healthcare costs. We will also interview patients and doctors to find out whether the colour chart is acceptable and will ensure that the intervention is followed properly by recording of a proportion of consultations. _x000D_ _x000D_ Our study team comprises a COPD specialist, a specialist in integrated care for COPD, a GP, public health experts, two patients, a health economist, a sociologist and members of our University’s clinical trials unit. All of the team have experience of conducting clinical trials, including those in primary care. We estimate the study will complete in 4 years.

Lay abstract: Research question: What is the effectiveness of sputum colour charts alongside a self-management (SM) plan to guide antibiotic self-treatment by patients with acute exacerbations of COPD?_x000D_ Background: COPD exacerbations (AECOPD) are characterized by increased sputum volume, purulence and breathlessness. Patients are encouraged to recognize and treat AECOPD as part of a SM plan. Even though only half of AECOPD are caused by bacteria such SM plans generally advocate use of antibiotics and steroids for all events, which implies overuse of antibiotics occurs, raising risk of resistance. Sputum colour relates closely to bacterial load thus could be used to determine whether antibiotics are appropriate. This pragmatic RCT will test whether use of a sputum colour chart is safe, effective and cost-effective in UK primary care_x000D_ _x000D_ Objectives_x000D_ 1 Assess whether use of the Bronkotest® sputum colour chart alongside a SM plan and rescue pack containing 5 days of antibiotic and steroid treatment (the intervention) is safe to use in primary care, as defined by non-inferiority, compared to use of the plan and pack alone (usual care) for rate of hospital admission for AECOPD at 12 months_x000D_ 2 Assess whether the intervention reduces self-reported and GP confirmed antibiotic use, and adverse events related to antibiotics compared to usual care. _x000D_ 3 Assess the effects of the intervention on treatment failure, time to next AECOPD after a self-managed event, unreported AECOPD rate (AECOPD not reported to a healthcare professional), number of unscheduled GP attendances, rate of 30 and 90 day AECOPD readmissions, and quality of life (SGRQ, EQ-5D-5L)_x000D_ 4 Describe the effect of the intervention on antibiotic resistance patterns in sputum_x000D_ 5 Determine cost-effectiveness of the intervention_x000D_ _x000D_ Methods: This is an individually randomized, controlled trial in 2954 patients with COPD who have had =2 AECOPD or =1 hospital admission for AECOPD in the preceding year, recruiting from approximately 80 GP practices in Birmingham and Greater Manchester, randomizing in a 1:1 ratio between the intervention and usual care. Primary outcome is rate of hospital admission for AECOPD. Assuming a 1-sided significance level of 2.5% and a true success rate in each group of 65%, with a non-inferiority margin of 6 percentage points the study has 90% power to detect non-inferiority of the intervention. The trials unit’s web based randomization algorithm minimizes on factors influencing AECOPD rate and hospital admission such as FEV1, chronic bronchitis and age. Secondary outcomes are listed in objectives 2-4 and include AECOPD rate and quality of life. Nested sub-studies examining daily symptoms via an e-diary (n=300) and sputum culture (n~1200) will assess unreported AECOPD rate and antibiotic resistance respectively. A process evaluation will include assessment of reach, trial fidelity and acceptability of the intervention. The latter will be assessed using qualitative research methods with patients and staff (n=60), incorporating co-analysis by patients_x000D_ _x000D_ Timelines for delivery: 4 years, comprising 6 month set-up, 2 years enrolment, 1 year follow up, 6 months analysis. Internal pilot will confirm sample size calculations and test methods of data capture_x000D_ _x000D_ Anticipated impact and dissemination: Dissemination will occur through conferences and publications, as well as through our PPI group and newsletter. Impact is anticipated through updates to UK COPD guidance around SM plans for AECOP

Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: RESPIRATORY