Trial to Evaluate Beta-Lactam Antimicrobial Therapy of Community Acquired Pneumonia in Children

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02891915
• Collaborator: (none)
• Enrollment: 385
• Locations: 9
• Arms: 2
• Actual Duration (Months): 36.4
• Patients Per Site: 42.8
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Pneumonia	Drug: Amoxicillin; Drug: Amoxicillin-clavulanate; Drug: Cefdinir; Other: Placebo	Phase 4

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 385 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Dec 2, 2016
• Actual Primary Completion Date: Dec 16, 2019
• Actual Study Completion Date: Dec 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Short 200 subjects will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo	Drug: Amoxicillin; Amoxicillin is an aminopenicillin antibiotic; Drug: Amoxicillin-clavulanate; 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.; Drug: Cefdinir; Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.; Other: Placebo; Placebo
Active Comparator: Standard 200 subjects will receive a standard course of the initially prescribed antibiotic( Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days	Drug: Amoxicillin; Amoxicillin is an aminopenicillin antibiotic; Drug: Amoxicillin-clavulanate; 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.; Drug: Cefdinir; Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.

Outcome Measures

Primary Outcome Measures

1. Desirability of Outcome Ranking (DOOR) [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 Outcome Measures

1. Desirability of Outcome Ranking (DOOR) [Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)]

   DOOR is a composite endpoint created using clinical outcomes from the first 18 days and at Outcome Assessment Visit #2 (OAV #2). It is based on adequate clinical response at OAV #2, solicited symptoms from first 18 days and number of days of antibiotics use for worsening pneumonia from the first 18 days of the study.

2. Resolution of Symptoms (a Component of DOOR) [Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)]

   This table provides number and percentage of subjects who experienced lack of resolution of symptoms by their OAV #1.

3. Resolution of Symptoms (a Component of DOOR) [Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)]

   This table provides number and percentage of subjects who experienced lack of resolution of symptoms by their OAV #2.

4. Adequate Clinical Response Rates (a Component of DOOR) [Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)]

   Lack of adequate clinical response at OAV #1 is defined as the presence of a medically attended visit to an Emergency Department (ED) or outpatient clinic or hospitalization or receipt of non-study antibiotics or surgical procedures for persistent or worsening pneumonia from Day 1 to Day 5.

5. Adequate Clinical Response Rates (a Component of DOOR) [Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)]

   Lack of adequate clinical response at OAV #2 is defined as the presence of a medically attended visit to an ED or outpatient clinic or hospitalization or receipt of non-study antibiotics or surgical procedures for persistent or worsening pneumonia from Day 1 to Day 18.

6. Number of Participants Reporting Solicited Symptoms [Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)]

   This table summarizes the number and percentage of subjects experiencing any solicited events of mild, moderate or severe severity from Day 1 to Day 5

7. Number of Participants Reporting Solicited Symptoms [Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)]

   This table summarizes the number and percentage of subjects experiencing any solicited events of mild, moderate or severe severity from Day 1 to Day 18

8. Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits [Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)]

   This table provides number and percentage of subjects who received non-study antibiotics for any use from Day 1 to Day 5

9. 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)]

   This table provides number and percentage of subjects who received non-study antibiotics for any use from Day 1 to Day 18

10. Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits [Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)]

    This table provides number and percentage of subjects who received non-study antibiotics for any reason from Day 1 to Day 5

11. Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits [Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)]

    This table provides number and percentage of subjects who received non-study antibiotics for any reason from Day 1 to Day 18

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 71 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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

1. Ability of a parent or guardian to understand and comply with the study procedures and be available for all study visits

2. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Children's of Alabama - Infectious Diseases/Virology	Birmingham	Alabama	United States	35233-1711
2	Arkansas Children's Hospital - Infectious Diseases	Little Rock	Arkansas	United States	72202-3500
3	University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases	Louisville	Kentucky	United States	40202
4	Washington University School of Medicine in St. Louis - Infectious Diseases	Saint Louis	Missouri	United States	63110-1010
5	Duke Human Vaccine Institute - Duke Vaccine and Trials Unit	Durham	North Carolina	United States	27704
6	Cincinnati Children's Hospital Medical Center - Infectious Diseases	Cincinnati	Ohio	United States	45229-3039
7	Children's Hospital of Philadelphia - The Center for Pediatric Clinical Effectiveness	Philadelphia	Pennsylvania	United States	19104-3309
8	Children's Hospital of Pittsburgh of UPMC - General Academic Pediatric	Pittsburgh	Pennsylvania	United States	15213-3205
9	Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center	Nashville	Tennessee	United States	37232-2573

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 14, 2018
• Statistical Analysis Plan - Feb 24, 2020

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT02891915
• Other Study ID Numbers: 14-0079; HHSN272201300023I
• First Posted: Sep 8, 2016
• Last Update Posted: Feb 3, 2021
• Last Verified: Apr 5, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Antimicrobial; Beta-Lactam; Pneumonia; Short Course; Standard Course; Therapy
• Additional relevant MeSH terms: Pneumonia; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination; Cefdinir

Study Results

Participant Flow

Recruitment Details	Children, males and females, aged 6-71 months who are diagnosed with Community Acquired Pneumonia (CAP) and initially treated in outpatient clinics, urgent care facilities, and emergency departments were enrolled. Participants were enrolled between 02DEC2016 and 22NOV2019.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Period Title: Overall Study
STARTED	192	193
COMPLETED	179	181
NOT COMPLETED	13	12

Baseline Characteristics

Arm/Group Title	Short Course	Standard Course	Total
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic( Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.	Total of all reporting groups
Overall Participants	192	193	385
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	34.6 (16.6)	36.8 (17.8)	35.7 (17.2)
Age, Customized (Count of Participants)
< 24 Months	55 28.6%	56 29%	111 28.8%
24-71 Months	137 71.4%	137 71%	274 71.2%
Sex: Female, Male (Count of Participants)
Female	97 50.5%	93 48.2%	190 49.4%
Male	95 49.5%	100 51.8%	195 50.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	15 7.8%	18 9.3%	33 8.6%
Not Hispanic or Latino	176 91.7%	173 89.6%	349 90.6%
Unknown or Not Reported	1 0.5%	2 1%	3 0.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 2.1%	4 2.1%	8 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	48 25%	51 26.4%	99 25.7%
White	121 63%	118 61.1%	239 62.1%
More than one race	15 7.8%	17 8.8%	32 8.3%
Unknown or Not Reported	4 2.1%	3 1.6%	7 1.8%
Region of Enrollment (participants) [Number]
United States	192 100%	193 100%	385 100%
Region of Enrollment (Count of Participants)
Arkansas Children's Hospital	8 4.2%	5 2.6%	13 3.4%
Children's Hospital of Philadelphia	59 30.7%	63 32.6%	122 31.7%
Children's Hospital of Pittsburgh	67 34.9%	62 32.1%	129 33.5%
Cincinnati Children's Hospital	2 1%	2 1%	4 1%
Duke University	23 12%	20 10.4%	43 11.2%
University of Alabama at Birmingham-Pediatrics	1 0.5%	6 3.1%	7 1.8%
Vanderbilt University Medical Center	16 8.3%	16 8.3%	32 8.3%
Washington University	16 8.3%	19 9.8%	35 9.1%
Initial Antibiotic (Count of Participants)
Amoxicillin	176 91.7%	174 90.2%	350 90.9%
Amoxicillin Clavulanate	10 5.2%	10 5.2%	20 5.2%
Cefdinir	6 3.1%	9 4.7%	15 3.9%
Initial Site of Treatment (Count of Participants)
ED	41 21.4%	40 20.7%	81 21%
Out-Patient/Urgent Care	151 78.6%	153 79.3%	304 79%

Outcome Measures

1. Primary Outcome

Title	Desirability of Outcome Ranking (DOOR)
Description	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.
Time Frame	Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) Population: All randomized subjects that were still eligible on Day 1 of the study. Analysis of DOOR will use all subjects in the ITT population. Subjects with missing values of DOOR will have their values imputed. However, summaries of observed ordinal clinical response values presented below are based on complete data without imputation.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	170	174
Adequate clinical response with resolution of symptoms and no adverse events	97 50.5%	107 55.4%
Adequate clinical response with resolution of symptoms and with mild adverse events	47 24.5%	42 21.8%
Adequate clinical response with resolution of symptoms and with moderate adverse events	14 7.3%	10 5.2%
Adequate clinical response with resolution of symptoms and with severe adverse events	0 0%	2 1%
Adequate clinical response with persistent symptoms of fever, tachypnea, or cough	10 5.2%	12 6.2%
Lack of adequate clinical response with ED/clinic visit but no hospitalization	2 1%	1 0.5%
Lack of adequate clinical response with hospitalization	0 0%	0 0%
Death from any cause	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Short Course, Standard Course
	Comments	Null: the sum of the probability that a subject assigned to the 5-day arm will have a higher DOOR (higher DOOR is a lower value and is superior) than if assigned to the 10-day arm plus one-half the probability of equal DOORs is 50% (i.e., no difference in DOOR).
	Type of Statistical Test	Superiority
	Comments	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.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Missing DOOR values at OAV #1 were first imputed using linear regression using baseline covariates and available DOOR components as covariates.
	Method	Wilcoxon (Mann-Whitney)
	Comments	The Mann-Whitney test was run on the multiple imputed datasets to generate estimates of DOOR probability and p-value
Method of Estimation	Estimation Parameter	Pr (Higher DOOR in Short-Course)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.63 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Desirability of Outcome Ranking (DOOR)
Description	DOOR is a composite endpoint created using clinical outcomes from the first 18 days and at Outcome Assessment Visit #2 (OAV #2). It is based on adequate clinical response at OAV #2, solicited symptoms from first 18 days and number of days of antibiotics use for worsening pneumonia from the first 18 days of the study.
Time Frame	Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)

Outcome Measure Data

Analysis Population Description

ITT Population: All randomized subjects that were still eligible on Day 1 of the study. Analysis of DOOR will use all subjects in the ITT population. Subjects with missing values of DOOR will have their values imputed. However, summaries of observed ordinal clinical response values presented below are based on complete data without imputation.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	163	167
Adequate clinical response with resolution of symptoms and no solicited events	73 38%	81 42%
Adequate clinical response with resolution of symptoms and with mild solicited events	53 27.6%	51 26.4%
Adequate clinical response with resolution of symptoms and with moderate solicited events	25 13%	20 10.4%
Adequate clinical response with resolution of symptoms and with severe solicited events	3 1.6%	4 2.1%
Adequate clinical response with persistent symptoms of fever, tachypnea, or cough	7 3.6%	8 4.1%
Lack of adequate clinical response with ED/clinic visit but no hospitalization	2 1%	3 1.6%
Lack of adequate clinical response with hospitalization	0 0%	0 0%
Death from any cause	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Short Course, Standard Course
	Comments	Null: the sum of the probability that a subject assigned to the 5-day arm will have a higher DOOR (higher DOOR is a lower numerical value and is superior) than if assigned to the 10-day arm plus one-half the probability of equal DOORs is 50% (i.e., no difference in DOOR).
	Type of Statistical Test	Superiority
	Comments	Testing whether Short course is superior to Standard course based on DOOR at OAV #2
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Missing DOOR values at OAV #2 were first imputed using linear regression using baseline covariates and available DOOR components as covariates
	Method	Wilcoxon (Mann-Whitney)
	Comments	The Mann-Whitney test was run on the multiple imputed datasets to generate estimates of DOOR probability and p-value.
Method of Estimation	Estimation Parameter	Pr (Higher DOOR in Short-Course)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.57 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Resolution of Symptoms (a Component of DOOR)
Description	This table provides number and percentage of subjects who experienced lack of resolution of symptoms by their OAV #1.
Time Frame	Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	170	174
Lack of Resolution of Symptoms	12 6.3%	13 6.7%
Fever	2 1%	1 0.5%
Elevated respiratory rate	2 1%	7 3.6%
Cough	7 3.6%	4 2.1%

4. Secondary Outcome

Title	Resolution of Symptoms (a Component of DOOR)
Description	This table provides number and percentage of subjects who experienced lack of resolution of symptoms by their OAV #2.
Time Frame	Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	163	167
Lack of Resolution of Symptoms	9 4.7%	11 5.7%
Fever	0 0%	3 1.6%
Elevated respiratory rate	2 1%	1 0.5%
Cough	6 3.1%	5 2.6%

5. Secondary Outcome

Title	Adequate Clinical Response Rates (a Component of DOOR)
Description	Lack of adequate clinical response at OAV #1 is defined as the presence of a medically attended visit to an Emergency Department (ED) or outpatient clinic or hospitalization or receipt of non-study antibiotics or surgical procedures for persistent or worsening pneumonia from Day 1 to Day 5.
Time Frame	Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	170	174
Lack of Adequate Clinical Response	2 1%	1 0.5%
ED or Clinic Visit	2 1%	1 0.5%
Receipt of Non-Study Antibiotic	2 1%	1 0.5%
Hospitalization	0 0%	0 0%
Surgical Procedure	0 0%	0 0%

6. Secondary Outcome

Title	Adequate Clinical Response Rates (a Component of DOOR)
Description	Lack of adequate clinical response at OAV #2 is defined as the presence of a medically attended visit to an ED or outpatient clinic or hospitalization or receipt of non-study antibiotics or surgical procedures for persistent or worsening pneumonia from Day 1 to Day 18.
Time Frame	Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	163	167
Lack of Adequate Clinical Response	2 1%	3 1.6%
ED or Clinic Visit	4 2.1%	2 1%
Receipt of Non-Study Antibiotic	2 1%	3 1.6%
Hospitalization	0 0%	0 0%
Surgical Procedure	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants Reporting Solicited Symptoms
Description	This table summarizes the number and percentage of subjects experiencing any solicited events of mild, moderate or severe severity from Day 1 to Day 5
Time Frame	Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	170	174
Any Event	74 38.5%	68 35.2%
Irritability	52 27.1%	43 22.3%
Vomiting	11 5.7%	11 5.7%
Diarrhea	23 12%	21 10.9%
Allergic Reaction	15 7.8%	15 7.8%
Stomatitis	1 0.5%	3 1.6%
Candidiasis	4 2.1%	4 2.1%

8. Secondary Outcome

Title	Number of Participants Reporting Solicited Symptoms
Description	This table summarizes the number and percentage of subjects experiencing any solicited events of mild, moderate or severe severity from Day 1 to Day 18
Time Frame	Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	163	167
Any Event	91 47.4%	89 46.1%
Irritability	67 34.9%	60 31.1%
Vomiting	19 9.9%	24 12.4%
Diarrhea	33 17.2%	30 15.5%
Allergic Reaction	22 11.5%	21 10.9%
Stomatitis	1 0.5%	6 3.1%
Candidiasis	7 3.6%	7 3.6%

9. Secondary Outcome

Title	Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits
Description	This table provides number and percentage of subjects who received non-study antibiotics for any use from Day 1 to Day 5
Time Frame	Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	170	174
ED or Clinic Visit	2 1%	1 0.5%
Receipt of Non-Study Antibiotic	2 1%	1 0.5%

10. Secondary Outcome

Title	Number of Participants Receiving Non-study Systemic Antibiotics for Persistent or Worsening Pneumonia During Medically Attended Visits
Description	This table provides number and percentage of subjects who received non-study antibiotics for any use from Day 1 to Day 18
Time Frame	Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	163	167
ED or Clinic Visit	4 2.1%	2 1%
Receipt of Non-Study Antibiotic	2 1%	3 1.6%

11. Secondary Outcome

Title	Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits
Description	This table provides number and percentage of subjects who received non-study antibiotics for any reason from Day 1 to Day 5
Time Frame	Outcome Assessment Visit 1 (Study Day 8 +/- 2 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #1. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #1, and completed OAV #1 with non-missing data for all DOOR components at OAV #1.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	170	174
ED or Clinic Visit	8 4.2%	7 3.6%
Receipt of Non-Study Antibiotic	7 3.6%	2 1%

12. Secondary Outcome

Title	Number of Participants Receiving Non-study Systemic Antibiotics for All Causes During Medically Attended Visits
Description	This table provides number and percentage of subjects who received non-study antibiotics for any reason from Day 1 to Day 18
Time Frame	Outcome Assessment Visit 2 (Study Day 22 +/- 3 days)

Outcome Measure Data

Analysis Population Description

Complete Case at OAV #2. This population is made of subjects who were treated with at least one dose of study product, did not terminate early from the study before OAV #2, and completed OAV #2 with non-missing data for all DOOR components at OAV #2.

Arm/Group Title	Short Course	Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo	Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
Measure Participants	163	167
ED or Clinic Visit	29 15.1%	32 16.6%
Receipt of Non-Study Antibiotic	18 9.4%	11 5.7%

Adverse Events

Time Frame	All adverse events (AEs) that occurred from Receipt of Study Agent (Day 1) through the final Outcome Assessment Visit (Day 22 +/- 3 days) were reported.
Adverse Event Reporting Description	Solicited AEs for both the Short and Standard course were assessed using MedDRA 22.0.
Arm/Group Title	Short Course		Standard Course
Arm/Group Description	Participants will receive a short course of the initially prescribed antibiotic for 5 days plus 5 days of matching placebo Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body. Placebo: Placebo		Participants will receive a standard course of the initially prescribed antibiotic (Amoxicillin, Amoxicillin-Clavulanate, Cefdinir) for 10 days Amoxicillin: Amoxicillin is an aminopenicillin antibiotic Amoxicillin-clavulanate: 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: Cefdinir is a cephalosporin antibiotic used to treat bacterial infections in many different parts of the body.
All Cause Mortality
	Short Course		Standard Course
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/192 (0%)		0/193 (0%)
Serious Adverse Events
	Short Course		Standard Course
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/192 (0%)		0/193 (0%)
Other (Not Including Serious) Adverse Events
	Short Course		Standard Course
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	98/192 (51%)		98/193 (50.8%)
Gastrointestinal disorders
Vomiting	23/192 (12%)	41	28/193 (14.5%)	62
Diarrhea	37/192 (19.3%)	124	34/193 (17.6%)	125
General disorders
Irritability	73/192 (38%)	370	65/193 (33.7%)	313
Immune system disorders
Allergic Reaction	22/192 (11.5%)	98	23/193 (11.9%)	156

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.