Twice Daily Treatment With Amoxicillin for Non-severe Community Acquired Pneumonia.

Study Overview
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Brief Summary
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The aim of this study will be to evaluate whether a twice-daily antibiotic regimen is non-inferior to a thrice-daily regimen for the treatment of non-severe community acquired pneumonia in children presenting at a paediatric Emergency Department (ED).

Detailed Description
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A single-center, non-blinded, pragmatic, randomized-controlled, non-inferiority clinical trial will be conducted in an urban, university-affiliated, tertiary care pediatric hospital ED. All patients three months old to 18 years of age who had symptoms and signs suggestive of non-severe community acquired pneumonia based on respiratory complaints and a pulmonary infiltrate identified by trained paediatricians or emergency physicians will be eligible to the present study. Study participants will be randomly allocated to receive either amoxicillin (90mg/kg per day) in twice or thrice daily regimen. Primary outcome will be treatment failure within 10 days of enrolment as defined by hospitalisation, need for a change in antibiotic (persistence of fever at 72 hours, clinical deterioration, comorbid condition or development of serious adverse reactions) and death. ED revisits within 72 hours, second course of antibiotic and clinical recurrence rates will be evaluated in the follow-up assessments as well as percent of adverse events encountered, number of days missed (work, school or daycare), coverage vaccination rate, protocol adherence and patient and parental satisfaction. The primary analysis will use an intention-to-treat approach. Per-protocol analysis will also be carried to compare the failure rate. Accounting to a maximal 10% drop-off rate, a sample size of 685 participants per arm was calculated to have a power of 90% to identify a difference of ≤ 5% with an alpha value of 0.05.

Official Title
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Treatment of Non-severe Community Acquired Pneumonia With Twice Daily Compared to Thrice Daily Regimen- A Non-inferiority Pragmatic Randomized-controlled Trial.

Conditions
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Community-acquired Pneumonia

Intervention / Treatment
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* Drug: Amoxicillin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients 3 months to 18 years of age attending the pediatric ED and diagnosed with a non-severe pneumonia, will be considered for enrolment. More precisely, the following inclusion criteria will be required: Presence of respiratory symptoms (cough and/or dyspnea) Presence of signs of pneumonia (tachypnea, abnormal breath sounds, crackles) Presence of fever Positive chest radiography as interpreted by the treating physician Exclusion Criteria: Any danger signs associated with pneumonia (severe indrawing, shock or severe dehydration, empyema, important pleural effusion, pulmonary abcess or pneumatocoele) History of anaphylactic or allergic reaction to penicillin or amoxicillin according to the treating physician. History of a serious nonimmunoglobulin E-mediated reactions (eg, Stevens-Johnson syndrome or toxic epidermal necrolysis) attributed to amoxicilin. Caregiver unable to provide consent (language barrier or lack of caregiver presence) Underlying unstable chronic illness (ie. cystic fibrosis, immune suppression, active tuberculosis, bronchiectasis or active pulmonary malignancies) Persistent/chronic pneumonia syndromes (with symptoms for >2 weeks), suspected by the physician to be caused by atypical pathogens, hospital- acquired pneumonia (been hospitalized within 2 weeks prior to enrolment), aspiration pneumonia or recurrent pneumonias. Any history of receiving amoxicillin within the past month Need hospitalisation for any other reasons (ie. persistent vomiting, severe life-threatening infection such as septicaemia or meningitis requiring intravenous antimicrobial agents) Previous participation in study

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Twice a day regimen<br>Patients will received a prescription of amoxicillin (90mg/kg/day) divided in two doses daily. | Drug: Amoxicillin<br>* (90 mg/kg/day) twice daily<br>* Other names: Amoxil;|
| Active Comparator: Thrice a day regimen<br>Patients will received a prescription of amoxicillin (90mg/kg/day) divided in three doses daily. | Drug: Amoxicillin<br>* (90 mg/kg/day) twice daily<br>* Other names: Amoxil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical failure within 10 days of enrolment | As a primary outcome, clinical failure will be defined by any of the following occurring within 10 days of enrolment: Death or hospitalisation A need for a change in antibiotic according to the treating physician. In our settings, common reasons to change antibiotic are: Persistence of fever at 72h Clinical deterioration: • Clinical deterioration will include the development of lower chest-wall indrawing, central cyanosis, stridor while calm, or danger signs as defined by: inability to drink or breastfeed, convulsions, persistent vomiting, lethargy, or unconsciousness at any time during a child's treatment. Development of a comorbid condition such as a meningitis, bacteriemia, osteomyelitis or septic arthritis Allergic reaction | Day 10 (after enrolment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Emergency department revisit within 72 hours | Return to the emergency department in the following 72 hours | 72 hours | 
| Second course of antibiotic | Necessity of second course of antibiotics | 1 month | 
| Clinical recurrence | Another diagnosis of pneumonia | 1 month | 
| Adverse events | Any adverse event | 10 days | 
| Number of working days missed by caregivers or school/daycare days missed by patients | Total number of days missed by caregivers or school/daycare days missed by the parents | 1 month | 
| Patient's and parents satisfaction with the discharge instructions' provided and the ease of administration | Measured on a likert scale through a telephone survey | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-severe community-acquired pneumonia, Amoxicillin treatment, Twice daily antibiotic regimen