The Norwegian Antibiotics for Pneumonia in Children Study

Study Overview
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Brief Summary
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This study evaluates the effect of amoxicillin in the treatment of lower airway infections in preschool children. Half of the patients will receive amoxicillin, while the other half will receive placebo.

Detailed Description
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The overall objective of the study is to determine if antibiotic therapy is beneficial in children with pneumonia who do not have a highly suspicious bacterial infection, such as in lobar pneumonia. Secondary objective is to determine whether antibiotic use influence the microbial flora, including antibiotic resistance, in the airways in the short or medium long term. The study is a phase IV double-blind, placebo-controlled, multicenter, nationwide, randomized superiority trial of amoxicillin versus placebo in children aged 1-5 years of age with a lower respiratory infection.

Official Title
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The Norwegian Antibiotics for Pneumonia in Children Study

Conditions
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Lower Respiratory Tract Infection, Pneumonia Childhood

Intervention / Treatment
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* Drug: Amoxicillin
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 12-59 months Fever: a. Temperature ≥ 38.0 at inclusion or reported within the last 24 hours Tachypnoe, age specific 12-17mnd ≥ 46 breaths per minute 18-23mnd ≥ 40 breaths per minute 24-35mnd ≥ 34 breaths per minute 36-47mnd ≥ 29 breaths per minute 48-59mnd ≥ 27 breaths per minute ≥ 1 sign of lower airway inflammation Cough (at inclusion or reported within the last 6 hours) Chest retractions (jugular, intercoastally or subcoastally) Grunting respiration Nasal flaring Crepitations by pulmonary auscultation Hypoxia (SpO2 ≤ 90%) Weight between 6.0 and 28.0 kg. • Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations Exclusion Criteria: Clinical suspicion of bacterial pneumonia based upon a temperature ≥39.0°C and at least one of the following: Bronchial breathing sounds Unilaterally decreased breath sounds or unilateral percussion dullness Pulmonary lobar consolidation and/or radiological high suspicion of empyema on chest x-ray if this is obtained prior to inclusion in the trial. Evidence of any bacterial infection requiring systemic antibiotics, including, but not exclusively: Clinical septicaemia Urinary tract infection Meningitis Systemic antibiotics received within the last 7 days Pulmonary lobar consolidation and/or radiological high suspicion of empyema on chest x-ray if this is obtained prior to inclusion in the trial. History of any serious underlying disease that can increase the risk of bacterial pulmonary infections, including but not limited to: Haematological or oncological Immunodeficiency Congenital heart disease Neuromuscular impairment Development disorder, including Downs syndrome Bronchopulmonary dysplasia, cystic fibrosis, primary ciliary dyskinesia, poorly controlled asthma or other severe chronic lung diseases Signs of lower obstructive airways with both of the following present by auscultation: prolonged expiration and generalised expiratory wheeze Stridor by auscultation. History of known or suspected adverse reactions to amoxicillin, or any other betalactam Participating in another trial that might affect the current study Any reason why, in the opinion of the investigator, the patient should not participate (e.g. not able to comply with study procedures)

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study is a phase IV double-blind, placebo-controlled, multicenter, nationwide, randomized superiority trial of amoxicillin versus placebo in children aged 1-5 years of age with a lower respiratory infection.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amoxicillin<br>Amoxicillin 100mg/ml mixture (Imacillin), 0.25ml/kg every 8 hours for 7 days. | Drug: Amoxicillin<br>* Imacillin mixture<br>* Other names: Imacillin;|
| Placebo Comparator: Placebo<br>Placebo mixture 0.25ml/kg every 8 hours for 7 days | Drug: Placebos<br>* Placebo manufactured to mimic amoxicillin mixture (Imacillin)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapy Failure | Therapy failure as defined by attending physician, leading to end of intervention and administration of open-label antibiotics | Within 7 days after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thereapy failure leading to intravenous antibiotic therapy | Therapy failure as defined by attending physician, leading to intravenous antibiotic therapy | Within 7 days after inclusion | 
| Duration of fever | Duration of fever | Up to 21 days after inclusion | 
| Duration of symptoms of pneumonia | Duration of cough or respiratory distress (tachypnoe, retractions, grunting respiration or nasal flaring. | Up to 21 days after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumonia, pre-school children, antibiotics, amoxicillin