Every year, thousands of children with chest infections are prescribed antibiotics in GP surgeries, but no one has run a proper placebo-controlled trial to see if the drugs actually help. This matters because lower respiratory tract infections (LRTIs) are extremely common in children, and GPs currently have no solid evidence to guide whether to prescribe amoxicillin or not. The trial will randomly assign children aged 6 months to 12 years with uncomplicated LRTI to receive either amoxicillin or a placebo for seven days. The primary outcome is how long moderately bad symptoms last, measured through a validated symptom diary. The study also tracks complications, quality of life, and costs from an NHS perspective, and will build a decision model to account for the long-term cost of antibiotic resistance. If the trial finds no meaningful difference between amoxicillin and placebo, it could change prescribing guidelines across UK primary care, reducing unnecessary antibiotic use and slowing resistance. If antibiotics do shorten symptoms, the results will identify which children benefit most, allowing GPs to target treatment precisely. Either way, the trial fills a glaring evidence gap that has persisted for decades.
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Design: RCT nested in an observational study Setting: Primary care Prior Literature. Cochrane/Medline searches identified no placebo-controlled trials of antibiotics for children with uncomplicated Lower Respiratory Tract Infection (LRTI) Target population: Children 6 months to 12 years Health technologies: Amoxicillin 50mg/kg/24 hours (in divided doses for 7 days) or placebo Inclusion Criteria. Acute uncomplicated LRTI (acute cough as the most prominent symptom and lower tract symptoms/signs (sputum/’rattly chest’/coarse rhonchi;breathless;pain). Exclusion: Non-infective (e.g.reflux,PE) or croup (viral aetiology very likely). Those with clinically suspected pneumonia or very unwell and/or unwilling to be randomised will be invited to participate in an observational study collecting the same data. Baseline measures: structured history/examination; pulse oximetry;X ray (for clinically undetected consolidation); and optional samples: swabs (for bacteriology) and pinprick (for CRP and Full blood count). Measurement of costs/outcomes: Primary outcome: duration of moderately bad symptoms (from validated symptom diary). Secondary outcomes: symptom severity (days 2-4); the development of new or worsening symptoms; complications. Health related quality of life will be measured by proxy methods in which The Health Utilities Index (HUI-Mark III)and EuroQoL (EQ5D) will be completed by patients or carers (on days 1,3,7,14,21,28). Follow-up (at 1 month): measure lung function (if aged 6+). Sample size: A minimum of 503 children are required to detect a 3 day difference due to antibiotics with 80% power for both the primary subgroup (children with chest signs; alpha=0.05) and also secondary subgroups (alpha=0.01), assuming 75% follow-up. We assume chest signs occur among at least 40% of the children participating, and the remaining subgroups (sputum seen and/or heard by parents (’rattly chest’) or clinicians; history of fever; physician rating of being unwell; short of breath) are present among more than 50% of children. Analysis. Multiple linear regression models will provide estimates both overall and for subgroups and estimates of interaction with intervention by subgroup. In addition we will explore to what extent results from additional tests (bacteriology,bio markers, abnormalities on chest-X rays,etc)are potential effect modifiers, and will explore differences between the purely observational data set and the trial data and our other large observational cohorts (TARGET and 3C studies). We will conduct economic evaluation alongside the clinical trial. Costs will take an NHS and personal social service (PSS) perspective (primary analysis) and societal perspective (secondary analysis). Outcomes will be measured as costs per symptomatic day prevented and the incremental cost per QALY gained. Cost-effectiveness acceptability curves will also be produced. In addition, a decision analytic model will be developed to explore the cost-effectiveness implication over the long term and investigate the potential implication of the costs associated with antibiotic resistance. Project timetables. 0-12 months finalise R+D approval, site preparation/training, confirm feasibility/viability of procedures/recruitment rates/qualitative work/internal pilot(one site);13-47 months main recruitment and 1 month follow-up(all sites); 48-50 months data cleaning, analysis, write up. Assumptions: 20 children per annum will be approached in each practice.
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