The Procalcitonin-guided Antibiotics in Respiratory Infections (PARI) project in general practice – a study protocol

BACKGROUND: Antibiotic resistance is a global health challenge and the close correlation between antibiotic use and the development of resistance makes it essential to maintain a rational use of antibiotics. Most antibiotics are prescribed in general practice against acute respiratory tract infections (ARTI), even though most of these infections are of viral etiology. Thus, a safe method to substantially reduce unnecessary use of antibiotics in general practice is needed. Procalcitonin (PCT) is a precursor protein with very low circulating levels in the blood under physiological conditions. However, in response serious bacterial infection the level of PCT in the blood may increase significantly. Until recently, quantitative analyses of PCT was performed in hospital laboratories, impeding the implementation of PCT in primary care. Our aim is to determine whether it is possible to lower the use of antibiotics in patients presenting with symptoms of ARTI, without significantly prolonging the period of illness, by using a newly released PCT point-of-care test in general practice. METHODS: The Procalcitonin-Guided Antibiotics in Respiratory Infections (PARI) study is a randomized, single-blinded, non-inferiority, multi-practice intervention study comparing a PCT-group to a control group. Patients (N = 508) will be randomly assigned 1:1 to standard care or to the PCT group. The primary outcomes the duration of illness and symptoms from ARTI measured with the Acute Respiratory Tract Infection Questionnaire. Secondary outcomes include (1) Number of participants in each trial arm exposed to antibiotic treatment at index consultation (day 1) and within 30 days, (2) Number of participants in each trial arm with side effects from antibiotic treatment within 14 days, (3) Number of participants in each trial arm with re-consultations within 30 days, (4) Number of participants in each trial arm admitted to hospital (including diagnosis and mortality) within 30 days, (5) Characterization of biomarker (CRP and PCT) level at index consultation. Tertiary outcomes include patient and general practitioner satisfaction with the use of the PCT point-of-care test, and long-term follow-up. DISCUSSION: To our knowledge, this is the first study to examine a PCT point-of-care test in general practice with the aim of reducing the use of antibiotics in patients with symptoms of ARTI. Results of this study may prove important in targeting antibiotic treatment only to those patients who need it, thus contributing to limiting the spread of antibiotic resistance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04216277, date of registration: 2. of January 2020.