[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657697":3},{"organization":4,"outcomesModule":7,"designInfo":40,"detailedDescription":47,"studyPopulation":39,"armGroups":48,"interventions":59,"overallOfficials":65,"centralContacts":79,"locations":89,"responsibleParty":110,"collaborators":39,"id":113,"slug":114,"hasResults":115,"nctId":116,"briefTitle":117,"officialTitle":118,"acronym":119,"eligibilityCriteria":120,"healthyVolunteers":115,"sex":121,"minAge":122,"maxAge":123,"enrollmentInfo":124,"targetDuration":39,"studyType":127,"phases":128,"briefSummary":130,"conditions":131,"keywords":136,"overallStatus":92,"whyStopped":39,"lastUpdateSubmitDate":152,"lastUpdatePostDateStruct":153,"startDateStruct":156,"completionDateStruct":158,"leadSponsor":160,"locationsCount":161},{"fullName":5,"class":6},"University of Witwatersrand, South Africa","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":39},[9],{"measure":10,"description":11,"timeFrame":12},"Antibiotic use during hospitalisation","Antibiotic use among children hospitalised with lower respiratory tract infection, including antibiotic initiation, route of administration, duration of therapy, and early discontinuation of antibiotics during the index hospital admission.","From randomisation (day of admission) until hospital discharge (up to 28 days post-randomisation)",[14,18,22,26,29,32,36],{"measure":15,"description":16,"timeFrame":17},"Number of participants who die within 28 days of randomisation","Number of participants who die from any cause within 28 days after randomisation. This outcome will be compared between the intervention and routine care groups.","From randomisation through 28 days after randomisation",{"measure":19,"description":20,"timeFrame":21},"Antibiotic treatment cost per participant","Total cost of systemic antibiotic treatment received by each participant from randomisation until discharge (up to 28 days following randomisation) from the index hospitalisation. Antibiotic costs will be calculated using the antibiotics administered, duration of treatment, and applicable unit costs. Mean or median cost per participant will be compared between the intervention and routine care groups and reported in South African rand.","From randomisation until discharge from the index hospitalisation, up to 28 days",{"measure":23,"description":24,"timeFrame":25},"Number of participants readmitted to hospital within 28 days of randomisation","Number of participants who are readmitted to hospital for any cause following discharge from the index admission and within 28 days after randomisation. This outcome will be compared between the intervention and routine care groups.","From discharge from the index hospitalisation through 28 days after randomisation",{"measure":27,"description":28,"timeFrame":17},"Number of Participants Experiencing at Least One Adverse Event Within 28 Days of Randomisation","Number of participants who experience at least one adverse event within 28 days after randomisation, according to the adverse event definition specified in the study protocol. Participants experiencing more than one adverse event will be counted once for this participant-level outcome",{"measure":30,"description":31,"timeFrame":21},"Number of Participants Requiring Invasive Mechanical Ventilation","Number of participants who require escalation of care to invasive mechanical ventilation during the index hospital admission. This outcome will be compared between the intervention and routine care groups.",{"measure":33,"description":34,"timeFrame":35},"Number of Participants Hospitalised for More Than 7 Days","Number of participants whose index hospital admission exceeds 7 days. Duration of hospitalisation will be calculated from the date of hospital admission to the date of discharge.","During the index hospitalisation, assessed at discharge, up to 28 days",{"measure":37,"description":38,"timeFrame":21},"Hospitalisation cost per participant","Total hospitalisation cost per participant during the index hospital admission. Hospitalisation costs will be calculated using the duration and level of hospital care received and the applicable unit costs. Mean or median cost per participant will be compared between the intervention and routine care groups and reported in South African rand.",null,{"allocation":41,"interventionModel":42,"interventionModelDescription":43,"primaryPurpose":6,"observationalModel":39,"timePerspective":39,"maskingInfo":44},"RANDOMIZED","PARALLEL","Participants will be randomly assigned in a 1:1 ratio to either an intervention group or a routine care control group. Children in the intervention group will receive antibiotic prescribing guidance based on serial point-of-care C-reactive protein (CRP) measurements and repeated PREPARE clinical severity score assessments in addition to routine clinical evaluation. Children in the control group will receive standard clinical care according to existing hospital practice and national treatment guidelines. Antibiotic use, outcomes and healthcare related costs will be compared between the two parallel study arms.",{"masking":45,"maskingDescription":46,"whoMasked":39},"NONE","This is an open-label study with no masking. Participants will be randomized to either an intervention arm, in which antibiotic prescribing is guided by serial point-of-care CRP measurements and PREPARE clinical severity score assessments, or a routine care control arm. Treating clinicians and study personnel will be aware of treatment allocation because implementation of the intervention requires access to CRP results and severity scores to guide antibiotic use.","Antimicrobial resistance (AMR) has emerged as one of the most pressing global health threats and is driven largely by the inappropriate use of antibiotics. Strengthening antibiotic stewardship is therefore a critical public health priority to slow the emergence of resistant pathogens and preserve the effectiveness of existing therapies. Stewardship in inherently complex, particularly in the management of lower respiratory tract infections (LRTIs) in children. Optimising appropriate antibiotic use requires good clinical acumen, diagnostic accuracy, and sound clinical decision-making. This decision-making is influenced by multiple environmental, social, behavioural and psychological factors.\n\nLRTIs remain a leading cause of mortality and morbidity in children under five years of age, particularly in low- and middle-income countries (LMICs). Despite progress in pneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine coverage, LRTIs continue to account for a significant proportion of paediatric hospital admissions and deaths. There has been a marked shift in the aetiology of LRTIs over the last two decades, with a now greater proportion of LRTIs attributable to respiratory viruses and a reduced proportion caused by bacterial infections. Data from The Pneumonia Etiology Research for Child Health (PERCH) study demonstrated that viruses accounted for approximately two-thirds of childhood pneumonia cases, while bacteria accounted for approximately one-quarter.\n\nThe World Health Organisation (WHO) pneumonia case definition is intentionally highly sensitive in order to reduce mortality, particularly in resource-limited settings. Importantly, the WHO definition does not differentiate between viral, bacterial or mixed aetiology LRTI. Consequently, many children fulfilling the criteria for severe pneumonia receive antibiotic treatment despite the predominance of viral causes. This challenge is particularly relevant in infants and young children where bronchiolitis and bronchopneumonia frequently present with overlapping clinical features and are often difficult to distinguish clinically.\n\nAlthough bronchiolitis is generally managed with supportive care alone and bronchopneumonia is treated with antibiotics, clinicians frequently struggle to differentiate between these two conditions, resulting in over-prescribing of antibiotics. Diagnostic uncertainty, concerns regarding clinical deterioration, fear of missing serious bacterial infection, and limitations in available diagnostic tools all contribute to antibiotic prescribing decisions. While this approach may reduce the risk of undertreatment, it also contributes to unnecessary antibiotic exposure, increased healthcare costs, adverse drug effects, disruptions of the microbiome, and the development of antimicrobial resistance.\n\nClinical severity assessment tools may help identify children at higher risk of adverse outcomes. The Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) clinical severity score was derived from data obtained from more than 20 countries and has demonstrated good external validity in predicting pneumonia-related mortality among children aged 2-59 months hospitalised with pneumonia. The PREPARE score incorporates patient age, sex, weight-for-age z-score, body temperature, respiratory rate, level of consciousness, cyanosis, and oxygen saturation to produce a risk score that can assist with clinical risk stratification.\n\nWhile risk assessment tools may identify children at risk of severe disease and adverse outcomes, they do not determine disease aetiology. Point-of-care (POC) biomarkers may assist clinicians in differentiating between viral and bacterial infections. C-reactive protein (CRP) is an inflammatory biomarker that has been evaluated as a tool to guide antibiotic prescribing practices. Studies conducted in Uganda and Tanzania have demonstrated that CRP-guided management strategies can safely reduce antibiotic prescribing among children with respiratory illnesses in outpatient settings. However, evidence regarding CRP-informed risk-differentiated care among African children hospitalised with LRTI is lacking.\n\nThe implementation of a clinical severity scoring system alongside serial POC CRP testing may provide a structured strategy to support safe antibiotic prescribing while reducing unnecessary antibiotic use. To our knowledge, no studies have assessed the safety of biomarker-guided and severity-score-guided withholding or early termination of antibiotics among young African children hospitalised with LRTI.\n\nThe primary component of this study is a 12-month pragmatic, unblinded randomised controlled trial conducted at Chris Hani Baragwanath Academic Hospital (CHBAH), a large tertiary referral hospital in Soweto, South Africa. Children aged 2 to 24 months admitted with a clinician diagnoses of LRTI will be eligible for enrolment following written informed consent from a parent or legal guardian.\n\nParticipants will be randomised win a 1:1 ratio to either an intervention arm or routine care arm. Children allocated to the intervention arm will undergo a baseline assessment using a decision-making algorithm incorporating both the PREPARE clinical severity score and a POC CRP test. A conservative CRP threshold of less than 10mg\u002FL together with a PREPARE score of 4 or less will be used to identify children who are at low risk of adverse outcomes and more likely to have viral disease. Repeat PREPARE assessments and POC CRP measurements will be performed on days 1, 2 and 3 following enrolment.\n\nThe intervention is intended to support clinical decision-making regarding antibiotic initiation, continuation and early termination. Treating clinicians will retain the authority to override the algorithm at any time based on the patient's clinical condition to ensure patient safety.\n\nChildren allocated to the control arm will receive routine clinical care according to existing hospital and unit-specific practices. A baseline PREPARE score will be recorded for research purposes, but clinical management decisions will not be guided by the study algorithm. Participants will be followed throughout hospitalisation and until 28 days following randomisation. Data collected will include antibiotic use, duration of antibiotic exposure, route of administration, clinical outcomes, need for respiratory support, adverse events, readmissions and mortality,\n\nThe primary outcome is antibiotic use during hospitalisation, including whether antibiotics were initiated or withheld, route of administration, and duration of therapy. Secondary outcomes include death within 28 days of randomisation, hospital readmission within 28 days, serious adverse events, escalation of care to invasive ventilation, hospitalisation exceeding seven days, duration of oxygen supplementation, duration of antibiotic exposure, duration of hospital stay, escalation of antibiotic therapy, post-discharge antibiotic use, and clinical complications including sepsis, lung abscess, and empyema.\n\nIn addition to the randomised trial, a mixed-methods study will explore clinician attitudes, beliefs and behaviours regarding antibiotic prescribing for children hospitalised with LRTI. Despite awareness of antimicrobial stewardship principles, clinicians continue to over-prescribe antibiotics because of diagnostic uncertainty, fear of adverse outcomes, time constraints, parental expectations, influence of colleagues and senior clinicians, and limitations in diagnostic resources.\n\nThe qualitative component will be guided by the Theoretical Domains Framework (TDF) and will involve surveys, focus group discussions and semi-structured interviews among registrars and paediatricians working at CHBAH. The study aims to identify behavioural, social and environmental determinants of prescribing practices and to better understand barriers and facilitators to appropriate antibiotic use.\n\nA health economic analysis will also be undertaken to compare healthcare-related costs between the intervention and routine care groups, including antibiotic expenditure, duration of hospitalisation, level of care received, and costs associated with respiratory support. The study will determine whether the intervention leads to cost savings through reductions in antibiotic use and shorter hospital stays.\n\nThis study aims to determine the safety and effectiveness of combining point-of-care CRP testing with clinical severity assessment to support antibiotic prescribing decisions among children aged 2-24 months hospitalised with LRTI. In addition, it seeks to improve understanding of clinician prescribing behaviour and the contextual factors that influence antibiotic use. The findings will contribute to the evidence base for paediatric antimicrobial stewardship and may inform future implementation of biomarker-guided and severity-guided antibiotic prescribing strategies in resource-limited settings.",[49,55],{"label":50,"type":51,"description":52,"interventionNames":53},"Intervention arm: CRP- and PREPARE-Guided Antibiotic Use","EXPERIMENTAL","Participants will receive antibiotic prescribing guidance based on serial point-of-care CRP measurements and repeated PREPARE clinical severity score assessments in addition to routine clinical care.",[54],"Diagnostic Test: CRP- and PREPARE-guided Antibiotic Prescription",{"label":56,"type":57,"description":58,"interventionNames":39},"Control: Standard of Care","NO_INTERVENTION","Participants will receive routine clinical management according to existing hospital and unit-specific practice. Antibiotic prescribing decisions will be made by the treating clinical team without guidance from the study intervention, including point-of-care CRP testing and the PREPARE clinical severity score algorithm",[60],{"type":61,"name":62,"description":63,"armGroupLabels":64,"otherNames":39},"DIAGNOSTIC_TEST","CRP- and PREPARE-guided Antibiotic Prescription","Antibiotic prescribing is guided by serial point-of-care CRP measurements and repeated PREPARE clinical severity score assessments. A predefined algorithm incorporating CRP results and clinical severity assessment is used to support decisions regarding antibiotic initiation, continuation, and discontinuation in children hospitalised with lower respiratory tract infections.",[50],[66,69,72,76],{"name":67,"affiliation":5,"role":68},"Lucy N Wilson, MBBCh, MMED, FCPaed","PRINCIPAL_INVESTIGATOR",{"name":70,"affiliation":5,"role":71},"David P Moore, PhD","STUDY_DIRECTOR",{"name":73,"affiliation":74,"role":75},"Chris A Rees, PhD","Emory University","STUDY_CHAIR",{"name":77,"affiliation":78,"role":75},"Ziyaad Dangor, PhD","University of the Witwatersrand Vaccines and Infectious Diseases Analytics (Wits VIDA) Research Unit",[80,85],{"name":81,"role":82,"phone":83,"phoneExt":39,"email":84},"Lucy N Wilson, MBBCH, MMED, FCPaed","CONTACT","+27 72 326 7888","lucy.wilson@wits-vida.org",{"name":86,"role":82,"phone":87,"phoneExt":39,"email":88},"Ziyaad Dangor, MBBCh","+27 83 471 0933","ziyaad.dangor@wits-vida.org",[90],{"facility":91,"status":92,"city":93,"state":94,"zip":95,"country":96,"countryCode":97,"cosmosGeoPoint":98,"geoPoint":103,"contacts":104},"Chris Hani Baragwanath Academic Hospital","RECRUITING","Johannesburg","Gauteng","2198","South Africa","ZA",{"type":99,"coordinates":100},"Point",[101,102],28.04363,-26.20227,{"lat":102,"lon":101},[105,107,109],{"name":106,"role":82,"phone":83,"phoneExt":39,"email":84},"Lucy N Wilson, MBBCh, MMED",{"name":77,"role":82,"phone":39,"phoneExt":108,"email":88},"+27 83 471 093",{"name":67,"role":68,"phone":39,"phoneExt":39,"email":39},{"type":68,"investigatorFullName":111,"investigatorTitle":112,"investigatorAffiliation":5,"oldNameTitle":39,"oldOrganization":39},"Lucy Wilson","Specialist Paediatrician","100657697","optimising-antibiotic-use-for-paediatric-lower-respiratory-tract-infections-in-africa-100657697",false,"NCT07841691","Optimising Antibiotic Use for Paediatric Lower Respiratory Tract Infections in Africa","Optimising Antibiotic Use for Young African Children Hospitalised With Lower Respiratory Tract Infections: the Role of Biomarkers, Clinical Severity Scoring and Clinician Attitudes","BEACON","Inclusion Criteria:\n\n* Children between the ages of 2-24 months\n* Clinician diagnosis of lower respiratory tract infection (LRTI)\n\nExclusion Criteria:\n\n* Transferred from other hospitals with more than 24 hours of hospitalisation\n* Hospitalisation within the preceding 30 days","ALL","2 Months","24 Months",{"count":125,"type":126},400,"ESTIMATED","INTERVENTIONAL",[129],"NA","Lower respiratory tract infections (LRTIs) remain a leading cause of hospitalisation and death among young children in Africa. Although viral infections account for a substantial proportion of LRTIs, antibiotics are frequently prescribed because distinguishing between viral and bacterial infections can be challenging. This contributes to unnecessary antibiotic exposure and the rising global public health challenge of antimicrobial resistance.\n\nThis pragmatic, unblinded randomised controlled study will evaluate whether the combination of point-of-care (POC) C-reactive protein (CRP) testing and the PREPARE clinical severity score can safely reduce antibiotic use among children aged 2 to 24 months hospitalised with LRTI at Chris Hani Baragwanath Academic Hospital (CHBAH), South Africa. Participants will be randomly assigned in a 1:1 ratio to either the intervention group, where antibiotic decisions are guided by serial POC CRP measurements and repeated PREPARE severity assessments, or a control group receiving routine clinical care.\n\nThe primary objective of the study is to compare antibiotic use during hospitalisation between the intervention and control groups. Secondary objectives are to evaluate the safety of this approach by comparing mortality, hospital readmission within 28 days, adverse events, need for invasive ventilation, duration of hospitalisation, and other clinical outcomes between study groups. In addition, the study will compare healthcare-related costs, including antibiotic expenditure and costs associated with hospitalisation.\n\nA parallel mixed-methods component will explore clinician attitudes, beliefs, and determinants of antibiotic prescribing for children hospitalised with LRTI using surveys, focus groups discussions, and individual interviews informed by the Theoretical Domains Framework (TDF). Findings will help identify behavioural and system-level factors that influence antibiotic prescribing and inform future antimicrobial stewardship interventions.\n\nThis study aims to generate evidence on whether biomarker-guided and risk-stratified care can safely optimise antibiotic use among young African children hospitalised with LRTI while improving antimicrobial stewardship and reducing healthcare costs.",[132,133,134,135],"Lower Respiratory Tract Infection (LRTI)","Pneumonia","Bronchopneumonia","Bronchiolitis",[137,138,139,140,133,135,134,141,142,143,144,145,146,147,148,149,150,151,96],"Antimicrobial stewardship","Antibiotic prescribing","Lower respiratory tract infection","Antibiotic use","C-Reactive Protein","CRP","Point-of-care testing","PREPARE score","Clinical severity score","Risk stratification","Hospitalised children","Childhood pneumonia","Antimicrobial resistance","Clinician attitudes","Implementation science","2026-09-21",{"date":154,"type":155},"2026-09-25","ACTUAL",{"date":157,"type":155},"2026-05-27",{"date":159,"type":126},"2027-06-30",{"name":5,"class":6},1]