A Phase IV Double-Blind, Placebo-Controlled, Randomized Trial to Evaluate Short Course vs.Standard Course Outpatient Therapy of Community Acquired Pneumonia in Children (SCOUT-CAP)
Overview
- Phase
- Phase 4
- Intervention
- Amoxicillin
- Conditions
- Pneumonia
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 385
- Locations
- 9
- Primary Endpoint
- Desirability of Outcome Ranking (DOOR)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief 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)
Detailed Description
This is a multi-center, randomized, double-blind, placebo-controlled, superiority clinical trial evaluating short course (5 day) vs. standard course (10 day) of oral beta-lactam antibiotic therapy (amoxicillin, amoxicillin-clavulanate, cefdinir) for treatment of CAP in children 6-71 months of age who have clinically improved prior to enrollment. The study will randomize approximately 400 enrolled subjects to one of the two study arms (approximately 200 children in each arm) in order to reach 360 subjects completing Outcome Assessment Visit 1. Subjects will be randomized (1:1) to receive either a standard course of the initially prescribed antibiotic (10 days) or a short course of the initially prescribed antibiotic (5 days) plus 5 days of matching placebo. The study will recruit potential subjects from children who are diagnosed with CAP and who are initiated on oral beta-lactam therapy by healthcare providers in EDs, outpatient clinics, and urgent care centers at the study sites. Day -5 is defined as the date on which oral beta-lactam therapy is initiated for a diagnosis of CAP. Potential subjects will be identified at any time following clinical diagnosis of pneumonia. These subjects will be assessed for eligibility and enrolled on Day -3 to -1 of their initially prescribed oral beta-lactam therapy. Subjects may also be enrolled on Day 1 (the first day of receipt of study agent) provided they have not yet received any doses of the healthcare provider-prescribed antibiotic therapy for that day. The 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). The Secondary objectives are: 1) To compare the composite overall outcome (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 #2 (Study Day 22 +/- 3 days); 2) To compare the resolution of symptoms (a component of 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 Visits #1 and #2; 3) To compare the clinical response (a component of 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 Visits #1 and #2; 4) To compare solicited events (a component of 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 Visits #1 and #2; 5) To compare medically attended visits to Emergency Departments (ED) or outpatient clinics, hospitalizations, surgical procedures, and receipt of non-study systemic antibiotics (components of the clinical response) 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 Visits #1 and #2
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 6 - 71 months
- •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
- •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
- •Ability of a parent or guardian to understand and comply with the study procedures and be available for all study visits
- •Signed written informed consent by a parent or guardian
Exclusion Criteria
- •Treatment with any systemic antibiotic therapy within 7 days before the diagnosis of CAP
- •Initial therapy for CAP with combination antibiotic therapy
- •amoxicillin, amoxicillin/clavulanate or cefdinir plus one or more additional oral, intravenous, or intramuscular antibiotics
- •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
- •Presence of concomitant bacterial infection that requires \> 5 days of antibiotic therapy
- •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
- •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
- •Pneumonia due to S. aureus or group A streptococcus documented by positive blood culture or PCR, at the time of enrollment
Arms & Interventions
Short
200 subjects will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo
Intervention: Amoxicillin
Short
200 subjects will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo
Intervention: Amoxicillin-clavulanate
Short
200 subjects will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo
Intervention: Cefdinir
Short
200 subjects will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo
Intervention: Placebo
Standard
200 subjects will receive a standard course of the initially prescribed antibiotic( Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days
Intervention: Amoxicillin
Standard
200 subjects will receive a standard course of the initially prescribed antibiotic( Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days
Intervention: Amoxicillin-clavulanate
Standard
200 subjects will receive a standard course of the initially prescribed antibiotic( Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days
Intervention: Cefdinir
Outcomes
Primary Outcomes
Desirability of Outcome Ranking (DOOR)
Time Frame: Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)
DOOR is a composite endpoint created using clinical outcomes from the first 5 days and at Outcome Assessment Visit #1 (OAV #1). It is based on adequate clinical response at OAV #1, solicited symptoms from first 5 days and number of days of antibiotics use for worsening pneumonia from the first 5 days of the study.
Secondary Outcomes
- Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits(Outcome Assessment Visit 2 (Study Day 22 +/- 3 days))
- Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits(Outcome Assessment Visit 2 (Study Day 22 +/- 3 days))
- Adequate Clinical Response Rates (a Component of DOOR)(Outcome Assessment Visit 2 (Study Day 22 +/- 3 days))
- Number of Participants Reporting Solicited Symptoms(Outcome Assessment Visit 2 (Study Day 22 +/- 3 days))
- Desirability of Outcome Ranking (DOOR)(Outcome Assessment Visit 2 (Study Day 22 +/- 3 days))
- Resolution of Symptoms (a Component of DOOR)(Outcome Assessment Visit 2 (Study Day 22 +/- 3 days))