Title: Procalcitonin: Evaluation of Antibiotic use in COVID-19 Hospitalised patients. (PEACH)
Funder: Department of Health and Social Care

Abstract: THE PROBLEM_x000D_ Antibacterial agents (antibiotics) are usually used during treatment of patients with more severe COVID-19 even though COVID-19 is caused by a virus, and antibiotics don’t work against viruses. This is because doctors worry that there might be a bacterial infection on top of the viral infection, a so-called secondary infection, that is making matters worse. In fact, there is no good evidence to guide the use of antibiotics in COVID-19 and rates of secondary bacterial infection are thought to be low. The COVID-19 pandemic has therefore resulted in an unwanted increase in antibiotic use which will expose patients to more side effects, an increased risk of infection with superbugs and increase cost. This is a study about a blood test called procalcitonin which is used in many hospitals to help diagnose bacterial infections and guide antibiotic treatment. There is a lack of clear evidence to support its use in lung infections, which means some hospitals have used the procalcitonin test to guide antibiotic decisions in COVID-19, whilst others have not._x000D_ _x000D_ AIM OF THE RESEARCH_x000D_ Our main aim is to find out if use of the procalcitonin test in COVID-19 patients reduced antibiotics and/or improved patient outcomes, such as time in hospital or on intensive care, death rates, and infections with superbugs._x000D_ _x000D_ PATIENT AND PUBLIC INVOLVEMENT_x000D_ We have developed this study with input from people who survived intensive care, including COVID-19. One of them is a previously fit and healthy BAME man, which is a group at high risk of poor outcomes from COVID-19._x000D_ _x000D_ WHAT WILL WE DO?_x000D_ The study has 3 parts._x000D_ 1. We will find out which hospitals have used procalcitonin during the first wave of the pandemic and those that have not. Where it was used, we will find out how it was used, because the test can be used in different ways. We will look at antibiotic use across all acute hospitals and see if procalcitonin testing had an effect._x000D_ 2. We will use anonymised routinely collected information (held in NHS medical records) from patients who were admitted to hospital with confirmed COVID-19 infection to compare antibiotic use and patient outcomes in patients who had, or did not have a procalcitonin test. We will also interview doctors to find out if, and how, they feel that the procalcitonin test helped them make better decisions about antibiotics_x000D_ 3. Finally, we will look at the cost of testing and find out if procalcitonin testing is good value for money and what it adds to other tests._x000D_ _x000D_ We will seek ethical approval for the study before we collect the data. Only the research teams at each hospital will have access to patients’ records, and once the information is collected, it will be anonymised before sending outside the hospital. No identifiable information about patients will be sent outside their own hospital where they were cared for with COVID-19._x000D_ _x000D_ HOW WILL IT BENEFIT PATIENTS?_x000D_ We hope to find out if use of the procalcitonin test reduced antibiotics and/or improved patient outcomes, such as time in hospital or on intensive care, death rates, and infections with superbugs. Based on this information, we will produce guidelines for doctors on how best to use the procalcitonin test in patients with COVID-19 infection, so that antibiotics are started early if needed and stopped promptly if not needed, thus reducing side effects, antibiotic resistance and infections with superbugs.

Lay abstract: BACKGROUND: _x000D_ Although COVID-19 is caused by a virus, many patients receive antibiotics to treat possible secondary bacterial infection. In reality, secondary bacterial infection affects only 7-15% of COVID-19 patients. This indicates that many patients with COVID-19 have received unnecessary antibiotics putting them at risk of antibiotic resistant infections and exacerbating the threat of antibiotic resistance to the wider population. Procalcitonin (PCT) is an inflammatory marker measured in blood samples which can help diagnose bacterial infections. PCT has been used in many NHS hospitals during the first wave of the COVID-19 to support antibiotic prescribing decisions, and anecdotally was found to help control antibiotic overuse. Current NICE guidance acknowledges that PCT could be useful in this situation and encourages centres to participate in research and data collection._x000D_ The PEACH study will analyse patient-level and organisational-level data from hospital trusts that did and did not use PCT testing during first wave of the COVID-19 pandemic. It will determine whether and how PCT testing should be deployed to protect patients from antibiotic overuse if the NHS experience a second wave of COVID-19 infection._x000D_ DESIGN: A combination of 1. patient level and aggregated retrospective, multicentre, observational data studies, 2. qualitative research (interviews) and 3. health economic analysis._x000D_ SETTING: UK acute NHS hospital trusts_x000D_ TARGET POPULATION: Adults and adolescents >=16 years old admitted to hospital between 1/2/20 and 30/06/20 with a confirmed SARS-CoV-2 test._x000D_ WORK PLAN:_x000D_ Workpackage (WP) 1.1 Describe the introduction of PCT testing during COVID-19, into the patient pathway._x000D_ WP 1.2 Determine whether, at Trust level, having a COVID-19 pathway incorporating PCT testing modified the impact of the first COVID-19 wave on antibiotic use._x000D_ WP 2.1 Measure the difference in antibiotic use, length of stay, mortality, intensive care unit admission and resistant secondary bacterial infections between COVID-19 patients who did/did not have PCT testing at baseline._x000D_ WP 2.2 Explore the decision-making processes around the use of antibiotics and the feasibility and acceptability of PCT testing algorithms in the management of COVID-19. Identify the contextual factors and the key ingredients of successful implementation and normalisation of PCT algorithms in the management of COVID-19._x000D_ WP 2.3 Integrate and triangulate findings from qualitative and quantitative sources (WP1.1, 1.2, 2.1) to determine whether PCT testing influenced antibiotic use during the first wave of the COVID-19 pandemic._x000D_ WP3.1 Assess cost of illness per patient from COVID-19 in NHS Trusts that used PCT versus those that did not, from the NHS perspective._x000D_ WP 3.2 Calculate cost-saved per unit investment into PCT use due to reduced antibiotic duration, reduction of hospitalisations, ICU admission and other cost-savings._x000D_ WP3.3 Assess cost-benefit analysis of PCT use versus no PCT use in COVID-19 patients_x000D_ SAMPLE SIZE: Workpackage 1.2: including all acute NHS trusts, with no formal sample size calculation. WP2.1:retrospective observational study using patient-level data, using data from ~7000 COVID-19 patients across 11 NHS acute hospitals, around half of which will have had PCT testing. Based on a minimally important clinical difference in antibiotic duration of 1 day between PCT and non-PCT-tested patients, and SD of 6 days, 1500 matched patients will provide 90% power

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.1 INDIVIDUAL CARE NEEDS
Health categories: INFECTION