C reactive protein-guided prescription of antibiotics for children under 12 years with respiratory symptoms in Kyrgyzstan: protocol for a randomised controlled clinical trial with 14 days follow-up

Abstract

IntroductionWhile lower respiratory tract infections are the main cause of death for children under 5 globally, only a small proportion of children with respiratory tract infections need antibiotics. Overuse of antibiotics globally is leading to increasing rates of antibiotic resistance. In Kyrgyzstan, healthcare workers regularly prescribe antibiotics when clinical uncertainty is present to err on the side of caution. Targeting antibiotic use with biomarkers of inflammation such as C reactive protein (CRP) testing at the point-of-care test (POCT) has been shown to reduce antibiotic use in general, but only few studies have been done in children and no studies exist from Central Asia. This study aims to assess whether the use of a CRP POCT can safely decrease prescription of antibiotics for children with acute respiratory symptoms in primary level healthcare centres in Kyrgyzstan.Methods and analysisMulticentre, open-label, individually randomised, controlled clinical trial with 14 days follow-up (follow-up by phone on days 3, 7 and 14) in rural lowland Chui and highland Naryn regions of Kyrgyzstan. The population are children aged 6 months to 12 years attending the primary level healthcare centres during normal business hours with acute respiratory symptoms. CRP POCT equipment will be supplied to healthcare centres, along with a short training session in CRP use, including the interpretation of results to support the clinical evaluation of the child with acute respiratory infection. The primary outcomes are the proportion of patients prescribed an antibiotic within 14 days of index consultation (superiority analysis) and days to recovery (non-inferiority analysis). Secondary outcomes are antibiotics prescribed at index consultation, reconsultations, hospital admission and vital status within 14 days. Analysis of the first primary outcome, antibiotic use, will be intention to treat using a logistic regression model. Analysis of the second primary outcome, days to recovery, will be per protocol using a linear regression model and a non-inferiority margin of 1 day.Ethics and disseminationThe study was approved on 18 June 2021 by the Ethics Committee (ref: no. 1) of the National Centre of Maternity and Childhood Care, Bishkek, Kyrgyzstan. The results of the study regardless of the conclusion will be presented at international conferences and published in peer-reviewed scientific medical journals along with policy briefs and technical reports.Trial registration numberNCT05195866.

The Feasibility of C-Reactive Protein Point-of-Care Testing to Reduce Overuse of Antibiotics in Children with Acute Respiratory Tract Infections in Rural Kyrgyzstan: A Pilot Study

“…This pilot study was conducted to examine the feasibility and possible barriers of the methods and procedures intended to be used in the upcoming randomised controlled clinical (RCT) COORDINATE trial. 25 We were specifically interested in understanding issues related to the study protocol, randomisation, inclusion and exclusion criteria, enrolment, implementation of the intervention, data capture, loss to follow-up and study withdrawal rate. The general feasibility was assessed through the willingness of HCWs to carry out and follow the CRP POCT algorithm.…”

“…Inclusion criteria were age between 6 months and 12 years; parents/caregivers able and willing to comply with all study requirements; parents/caregivers able and willing to give informed consent; the patient had at least one of the following focal symptoms lasting for less than 2 weeks: cough, fast/difficult breathing, sore throat, shortness of breath, wheezing. 25 The study excluded very ill children where CRP POCT measurement would delay care, children with known immunosuppression or severe chronic disease, children with a positive SARS-CoV-2 rapid test, and children who had taken antibiotics within 24 hours before the consultation. 25…”

“…25 The study excluded very ill children where CRP POCT measurement would delay care, children with known immunosuppression or severe chronic disease, children with a positive SARS-CoV-2 rapid test, and children who had taken antibiotics within 24 hours before the consultation. 25…”