Trial to Evaluate Beta-Lactam Antimicrobial Therapy of Community Acquired Pneumonia in Children
Condition: Pneumonia
MeSH terms: Pneumonia
Intervention: Amoxicillin; Amoxicillin-clavulanate; Cefdinir; Placebo
Intervention description: Amoxicillin is an aminopenicillin antibiotic; A fixed-ratio combination of amoxicillin trihydrate, an aminopenicillin, and potassium clavulanate, a beta-lactamase inhibitor, used to treat a broad-spectrum of bacterial infections, especially resistant strains.; Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.; Placebo
Intervention MeSH terms: Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination; Cefdinir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 385.0
Sex: All
Minimum age: 6 Months
Maximum age: 71 Months
Healthy volunteers: No
Keywords: Antimicrobial; Beta-Lactam; Pneumonia; Short Course; Standard Course; Therapy

Summary:

      This is a multi-center, randomized, double-blind, placebo-controlled, superiority clinical
      trial will test the effectiveness of short (5-day) vs.standard (10-day) course therapy in
      children who are diagnosed with CAP and initially treated in outpatient clinics, urgent care
      facilities, and emergency departments. Primary objective is to compare the composite overall
      outcome (Desirability of Outcome Ranking, DOOR) among children 6-71 months of age with CAP
      assigned to a strategy of short course (5 days) vs standard course (10 days) outpatient
      beta-lactam therapy at Outcome Assessment Visit #1 (Study Day 8 +/- 2 days)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 6 - 71 months

          2. Provider diagnosis of CAP and prescription of antibiotic therapy with amoxicillin,
             amoxicillin-clavulanate, or cefdinir

             - amoxicillin or amoxicillin-clavulanate prescribed at a amoxicillin dose of 60
             mg/kg/day

             -- cefdinir prescribed at a minimum dose of 10 mg/kg/day

          3. Parental report of clinical improvement

             - based on lack of either subjective or known fever temperature >/= 38.3°C in the
             preceding 24 hours; current respiratory rate no greater than 50 breaths/minute (<2
             years of age) or breaths/minute (= / > 2 years of age); and current grade of cough < 3

          4. Ability of a parent or guardian to understand and comply with the study procedures and
             be available for all study visits

          5. Signed written informed consent by a parent or guardian

        Exclusion Criteria:

        1. Treatment with any systemic antibiotic therapy within 7 days before the diagnosis of CAP
        2. Initial therapy for CAP with combination antibiotic therapy

          -  amoxicillin, amoxicillin/clavulanate or cefdinir plus one or more additional oral,
             intravenous, or intramuscular antibiotics 3. History of anaphylaxis or severe drug
             allergy to amoxicillin, if prescribed amoxicillin or amoxicillin/clavulanic acid; or
             oral cephalosporin antibiotics (except cefaclor), if prescribed cefdinir 4. Presence
             of concomitant bacterial infection that requires > 5 days of antibiotic therapy 5.
             Radiographic findings (where applicable) of complicated pneumonia at presentation or
             any subsequent chest radiograph up to the time of enrollment

          -  clinically significant pleural effusion, lung abscess, or pneumatocele 6.
             Hospitalization for pneumonia during Day -5 to -1 of antibiotic therapy for CAP

          -  subjects who require serial clinical assessments, but are discharged within 24 hours
             will not be considered hospitalized and will not satisfy this exclusion criterion 7.
             Pneumonia due to S. aureus or group A streptococcus documented by positive blood
             culture or PCR, at the time of enrollment 8. History of pneumonia within the previous
             6 months 9. History of persistent asthma within the previous 6 months or current acute
             asthma exacerbation

          -  persistent asthma is defined as receiving daily asthma maintenance therapy such as
             inhaled corticosteroids, cromolyn, theophylline, or leukotriene receptor antagonists

             -- acute asthma exacerbation is defined as receiving concomitant bronchodilator
             therapy and systemic corticosteroids 10. Provider-diagnosis of aspiration pneumonia,
             bronchiolitis, or bronchitis 11. Surgery or other invasive procedures of the upper or
             lower airway (e.g., bronchoscopy, laryngoscopy) with general anesthesia or
             hospitalization </=7 days before diagnosis of CAP 12. History of an underlying chronic
             medical condition

          -  including chronic heart disease, chronic lung disease (except asthma), congenital
             anomalies of the airways or lung, cystic fibrosis, chronic renal disease including
             nephrotic syndrome, protein-losing enteropathy of any cause, severe malnutrition,
             neurocognitive disorders, metabolic disorders (including phenylketonuria), or genetic
             disorders (note: genetic syndromes such as Down syndrome and Edwards Syndrome are
             excluded; however, children with genetic disorders (e.g., hemophilia) but who do not
             have a genetic syndrome may not satisfy this particular exclusion criterion; it is
             important that children with such genetic disorders do not have symptoms and/or
             comorbidities that would pose additional risk to them nor jeopardize the adequacy of
             study assessments.) 13. History of a condition that compromises the immune system

          -  HIV infection, primary immunodeficiency, anatomic or functional asplenia; receipt of a
             hematopoietic stem cell or solid organ transplant at any time; receipt of
             immunosuppressive therapy including chemotherapeutic agents, biologic agents,
             antimetabolites or radiation therapy during the past 12 months; or daily use of
             systemic corticosteroids for more than 7 consecutive days during the past 14 days 14.
             Any other condition that in the judgment of the investigator precludes participation
             because it could affect the safety of the subject 15. Current enrollment in another
             clinical trial of an investigational agent 16. Previous enrollment in this trial