Trial Outcomes & Findings for Efficacy of Short-Course Antimicrobial Treatment for Children With Acute Otitis Media and Impact on Resistance (NCT NCT01511107)

Last Updated: 2017-10-06

Results Overview

Proportion of children initially diagnosed with AOM who experience treatment failure at or before the day 12-14 visit. TF is defined as substantial persistence or worsening of symptoms specifically attributable to AOM, or of otoscopic signs of AOM, after 72 hours from the time of randomization, such that additional antimicrobial therapy is deemed advisable. If a parent/legal guardian is unwilling to continue the assigned study product regimen, the participant will be categorized as TF. Should a participant be administered another systemic antibiotic while taking study medication or prior to Day 16, the participant will be considered a TF. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the tympanic membrane (TM) or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

520 participants

Primary outcome timeframe

From 72 hours after randomization until day 21 of the index episode. The mean day for this visit was 13.2.

Results posted on

2017-10-06

Participant Flow

Participant milestones

Participant milestones
Measure	Amoxicillin-Clavulanate, 10 Days Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
Overall Study STARTED	260	260
Overall Study COMPLETED	238	219
Overall Study NOT COMPLETED	22	41

Reasons for withdrawal

Reasons for withdrawal
Measure	Amoxicillin-Clavulanate, 10 Days Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
Overall Study Ineligible	3	2
Overall Study Lost to Follow-up	10	19
Overall Study Withdrawal by Subject	9	20

Baseline Characteristics

Efficacy of Short-Course Antimicrobial Treatment for Children With Acute Otitis Media and Impact on Resistance

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Amoxicillin-Clavulanate, 10 Days n=257 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=258 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.	Total n=515 Participants Total of all reporting groups
Age, Customized 6-11 months	129 participants n=5 Participants	132 participants n=7 Participants	261 participants n=5 Participants
Age, Customized 12-17 months	80 participants n=5 Participants	77 participants n=7 Participants	157 participants n=5 Participants
Age, Customized 18-23 months	48 participants n=5 Participants	49 participants n=7 Participants	97 participants n=5 Participants
Sex: Female, Male Female	115 Participants n=5 Participants	123 Participants n=7 Participants	238 Participants n=5 Participants
Sex: Female, Male Male	142 Participants n=5 Participants	135 Participants n=7 Participants	277 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=5 Participants	23 Participants n=7 Participants	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	233 Participants n=5 Participants	235 Participants n=7 Participants	468 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	110 Participants n=5 Participants	118 Participants n=7 Participants	228 Participants n=5 Participants
Race (NIH/OMB) White	116 Participants n=5 Participants	110 Participants n=7 Participants	226 Participants n=5 Participants
Race (NIH/OMB) More than one race	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Study Site Children's Hospital of Pittsburgh (CHP)	163 participants n=5 Participants	163 participants n=7 Participants	326 participants n=5 Participants
Study Site Children's Community Pediatrics	47 participants n=5 Participants	47 participants n=7 Participants	94 participants n=5 Participants
Study Site Kentucky Pediatric and Adult Research	47 participants n=5 Participants	48 participants n=7 Participants	95 participants n=5 Participants
Maternal Education Less than high school	31 participants n=5 Participants	26 participants n=7 Participants	57 participants n=5 Participants
Maternal Education High school graduate or equivalent	150 participants n=5 Participants	169 participants n=7 Participants	319 participants n=5 Participants
Maternal Education College graduate	76 participants n=5 Participants	62 participants n=7 Participants	138 participants n=5 Participants
Maternal Education Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Type of Health Insurance Private	84 participants n=5 Participants	75 participants n=7 Participants	159 participants n=5 Participants
Type of Health Insurance Public	171 participants n=5 Participants	179 participants n=7 Participants	350 participants n=5 Participants
Type of Health Insurance None	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Exposure to Other Children Not exposed	109 participants n=5 Participants	105 participants n=7 Participants	214 participants n=5 Participants
Exposure to Other Children Exposed	148 participants n=5 Participants	153 participants n=7 Participants	301 participants n=5 Participants
Acute Otitis Media Severity of Symptoms (AOM-SOS) Score 3-5	43 participants n=5 Participants	59 participants n=7 Participants	102 participants n=5 Participants
Acute Otitis Media Severity of Symptoms (AOM-SOS) Score 6-8	75 participants n=5 Participants	70 participants n=7 Participants	145 participants n=5 Participants
Acute Otitis Media Severity of Symptoms (AOM-SOS) Score 9-11	98 participants n=5 Participants	95 participants n=7 Participants	193 participants n=5 Participants
Acute Otitis Media Severity of Symptoms (AOM-SOS) Score 12-14	41 participants n=5 Participants	34 participants n=7 Participants	75 participants n=5 Participants
Mean AOM-SOS Score	8.6 AOM-SOS score STANDARD_DEVIATION 2.9 • n=5 Participants	8.2 AOM-SOS score STANDARD_DEVIATION 3.0 • n=7 Participants	8.4 AOM-SOS score STANDARD_DEVIATION 3.0 • n=5 Participants
Estimated severity of illness from pain and fever history only Likely nonsevere	111 participants n=5 Participants	121 participants n=7 Participants	232 participants n=5 Participants
Estimated severity of illness from pain and fever history only Likely severe	146 participants n=5 Participants	137 participants n=7 Participants	283 participants n=5 Participants
Laterality of Acute Otitis Media (AOM) Unilateral	136 participants n=5 Participants	126 participants n=7 Participants	262 participants n=5 Participants
Laterality of Acute Otitis Media (AOM) Bilateral	121 participants n=5 Participants	132 participants n=7 Participants	253 participants n=5 Participants
Degree of Tympanic Membrane Bulging Slight	35 participants n=5 Participants	45 participants n=7 Participants	80 participants n=5 Participants
Degree of Tympanic Membrane Bulging Moderate	137 participants n=5 Participants	135 participants n=7 Participants	272 participants n=5 Participants
Degree of Tympanic Membrane Bulging Marked	85 participants n=5 Participants	78 participants n=7 Participants	163 participants n=5 Participants
Streptococcus Pneumoniae (S pneumoniae) Sensitivity in Nasopharyngeal Cultures S pneumoniae absent	131 participants n=5 Participants	120 participants n=7 Participants	251 participants n=5 Participants
Streptococcus Pneumoniae (S pneumoniae) Sensitivity in Nasopharyngeal Cultures S pneumoniae present, susceptible	84 participants n=5 Participants	94 participants n=7 Participants	178 participants n=5 Participants
Streptococcus Pneumoniae (S pneumoniae) Sensitivity in Nasopharyngeal Cultures S pneumoniae present, intermediate	20 participants n=5 Participants	28 participants n=7 Participants	48 participants n=5 Participants
Streptococcus Pneumoniae (S pneumoniae) Sensitivity in Nasopharyngeal Cultures S pneumoniae present, resistant	21 participants n=5 Participants	16 participants n=7 Participants	37 participants n=5 Participants
Streptococcus Pneumoniae (S pneumoniae) Sensitivity in Nasopharyngeal Cultures Unknown, no culture	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Haemophilus Influenzae (H influenzae) Sensitivity in Nasopharyngeal Cultures H influenzae absent	172 participants n=5 Participants	197 participants n=7 Participants	369 participants n=5 Participants
Haemophilus Influenzae (H influenzae) Sensitivity in Nasopharyngeal Cultures H influenzae present, susceptible	53 participants n=5 Participants	37 participants n=7 Participants	90 participants n=5 Participants
Haemophilus Influenzae (H influenzae) Sensitivity in Nasopharyngeal Cultures H influenzae present, nonsusceptible	31 participants n=5 Participants	24 participants n=7 Participants	55 participants n=5 Participants
Haemophilus Influenzae (H influenzae) Sensitivity in Nasopharyngeal Cultures Unknown, no culture	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: From 72 hours after randomization until day 21 of the index episode. The mean day for this visit was 13.2.

Population: The analysis was intent to treat (ITT). The number of participants is equal to the number of children randomized \& eligible who had a clinical assessment at or before the day 12-14 visit.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=238 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=229 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit Specific to the Index Episode of AOM Treatment failure	39 participants	77 participants
The Distribution of Children Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit Specific to the Index Episode of AOM Treatment success	199 participants	152 participants

SECONDARY outcome

Timeframe: From 72 hours after the AOM recurrence was diagnosed until day 21 of the recurrence. The mean day for this visit was 13.3.

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible who had a clinical assessment at or before the day 12-14 visit following an AOM recurrence.

Proportion of AOM recurrences resulting in treatment failure at or before the day 12-14 visit. TF is defined as substantial persistence or worsening of symptoms specifically attributable to AOM, or of otoscopic signs of AOM, after 72 hours from the time of the recurrence, such that additional antimicrobial therapy is deemed advisable. If a parent/legal guardian is unwilling to continue the assigned study product regimen, the participant will be categorized as TF. Should a participant be administered another systemic antibiotic while taking study medication or prior to Day 16, the participant will be considered a TF. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the TM or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=133 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=102 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of AOM Recurrences Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit Treatment failure	25 recurrence	29 recurrence
The Distribution of AOM Recurrences Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit Treatment success	108 recurrence	73 recurrence

SECONDARY outcome

Timeframe: The day 12-14 visit. The mean day for this visit was 13.3.

Population: The analysis was ITT. The participants are randomized \& eligible children having a NP culture at enrollment that is negative for both S pn and H flu and a NP culture at the day 12-14 visit which is either positive (+) for \>=1 penicillin nonsusceptible pathogen OR pathogen negative (-) or + only for \>=1 penicillin susceptible pathogen.

AOM pathogens are defined as Streptococcus pneumoniae (S pn) or Haemophilus Influenzae (H flu). In the case of S pn, susceptibility to penicillin was determined as follows: When minimum inhibitory concentration (MIC) was available, susceptible was defined as MIC \<0.1 µg/mL, intermediate as MIC 0.1 to 1 µg/mL, and resistant as MIC \>1 µg/mL. When MIC was not available, susceptible was defined as showing oxacillin disk zone size \>20 mm, intermediate as zone size 9 to 20 mm, and resistant as zone size ≤8 mm. In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC \>1 µg/mL.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=75 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=72 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen + for nonsusceptible pathogen(s) day 12-14	15 participants	11 participants
The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen pathogen - or + only for susceptible day 12-14	60 participants	61 participants

SECONDARY outcome

Timeframe: The day 12-14 visit. The mean day for this visit was 13.4.

Population: The analysis was ITT. The participants are randomized \& eligible children having a NP culture at onset that is negative for both S pn and H flu and a NP culture at the day 12-14 visit which is either positive (+) for \>=1 penicillin nonsusceptible pathogen OR pathogen negative (-) or + only for \>=1 penicillin susceptible pathogen.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=46 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=32 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen + for nonsusceptible pathogen(s) day 12-14	12 recurrence	8 recurrence
The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen pathogen - or + only for susceptible day 12-14	34 recurrence	24 recurrence

SECONDARY outcome

Timeframe: The day 12-14 visit. The mean day for this visit was 13.2.

Population: The analysis was ITT. The participants are randomized \& eligible children having a NP culture at enrollment that is positive only for \>=1 susceptible pathogen \& a NP culture at the day 12-14 visit which is either positive (+) for \>=1 penicillin nonsusceptible pathogen OR pathogen negative (-) or + only for \>=1 penicillin susceptible pathogen.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=93 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=90 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen + for nonsusceptible pathogen(s) day 12-14	10 participants	12 participants
The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen pathogen - or + only for susceptible day 12-14	83 participants	78 participants

SECONDARY outcome

Timeframe: The day 12-14 visit. The mean day for this visit was 13.9.

Population: The analysis was ITT. The participants are randomized \& eligible children having a NP culture at onset that is positive (+) only for one or more susceptible pathogens \& a NP culture at the day 12-14 visit which is either + for \>=1 penicillin nonsusceptible pathogen OR pathogen negative (-) or + only for \>=1 penicillin susceptible pathogen.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=44 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=33 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen + for nonsusceptible pathogen(s) day 12-14	8 recurrence	6 recurrence
The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen pathogen - or + only for susceptible day 12-14	36 recurrence	27 recurrence

SECONDARY outcome

Timeframe: The end-of-treatment visit. The mean day for this visit was 13.6.

Population: The analysis was ITT. The participants are randomized \& eligible children having both a NP culture at enrollment that is positive (+) for one or more nonsusceptible pathogens \& a NP culture at the day 12-14 visit which is either + for \>=1 penicillin nonsusceptible pathogen OR pathogen negative (-) or + only for \>=1 penicillin susceptible pathogen.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=64 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=60 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Positive for One or More Nonsusceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen + for nonsusceptible pathogen(s) day 12-14	34 participants	28 participants
The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Positive for One or More Nonsusceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen pathogen - or + only for susceptible day 12-14	30 participants	32 participants

SECONDARY outcome

Timeframe: The end-of-treatment visit. The mean day for this visit was 13.4.

Population: The analysis was ITT. The participants are randomized \& eligible children having a NP culture at onset that is positive (+) for \>=1 nonsusceptible pathogen \& a NP culture at the day 12-14 visit which is either + for \>=1 penicillin nonsusceptible pathogen OR pathogen negative (-) or + only for \>=1 penicillin susceptible pathogen.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=33 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=29 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Positive for One or More Nonsusceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen + for nonsusceptible pathogen(s) day 12-14	17 recurrence	22 recurrence
The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Positive for One or More Nonsusceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen pathogen - or + only for susceptible day 12-14	16 recurrence	7 recurrence

SECONDARY outcome

Timeframe: Day 1 of study entry until day 365

Population: The analysis was ITT. The participants are randomized \& eligible children having both a NP culture at enrollment that is either pathogen negative or positive only for \>=1 susceptible pathogen and a NP culture at some time over the course of followup.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=181 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=177 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children Whose Nasopharyngeal (NP) Isolates at Enrollment Are Pathogen Negative or Positive Only for at Least One Susceptible Pathogen Who Become Colonized With Nonsusceptible Pathogens at Any Time Over the Course of Follow-up + for a nonsusceptible pathogen during followup	85 participants	78 participants
The Distribution of Children Whose Nasopharyngeal (NP) Isolates at Enrollment Are Pathogen Negative or Positive Only for at Least One Susceptible Pathogen Who Become Colonized With Nonsusceptible Pathogens at Any Time Over the Course of Follow-up - for a nonsusceptible pathogen during followup	96 participants	99 participants

SECONDARY outcome

Timeframe: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.

Population: The analysis was ITT. The participants are randomized \& eligible children with at least one follow-up, nonillness visit, with a nasopharyngeal (NP) culture which is either positive (+) for \>=1 penicillin nonsusceptible pathogens or positive (+) only for \>=1 penicillin susceptible pathogens or pathogen negative (-).

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=415 Visits Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=359 Visits Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of 6 Week Follow-up, Non-Illness Visits During the Respiratory Season at Which a Nonsusceptible Pathogen is Recovered + for nonsusceptible pathogen(s)	79 Visit	64 Visit
The Distribution of 6 Week Follow-up, Non-Illness Visits During the Respiratory Season at Which a Nonsusceptible Pathogen is Recovered pathogen - or + only for susceptible pathogen(s)	336 Visit	295 Visit

SECONDARY outcome

Timeframe: The day 12-14 visit specific to the index episode. The mean day for this visit was 13.4.

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible having a NP culture at the day 12-14 visit following the index episode.

In the case of S pn, susceptibility to penicillin was determined as follows: When minimum inhibitory concentration (MIC) was available, susceptible was defined as MIC \<0.1 µg/mL, intermediate as MIC 0.1 to 1 µg/mL, and resistant as MIC \>1 µg/mL. When MIC was not available, susceptible was defined as showing oxacillin disk zone size \>20 mm, intermediate as zone size 9 to 20 mm, and resistant as zone size ≤8 mm.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=233 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=222 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate S pn, nonsusceptible	23 participants	26 participants
The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate S pn, susceptible	5 participants	10 participants
The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate S pn, absent	205 participants	186 participants

SECONDARY outcome

Timeframe: The day 12-14 visit following a recurrence. The mean day for this visit was 13.6.

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible having a NP culture at the day 12-14 visit following an AOM recurrence.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=131 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=99 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate S pn, nonsusceptible	20 recurrence	25 recurrence
The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate S pn, susceptible	4 recurrence	6 recurrence
The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate S pn, absent	107 recurrence	68 recurrence

SECONDARY outcome

Timeframe: The day 12-14 visit specific to the index episode. The mean day for this visit was 13.4.

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible having a NP culture at the day 12-14 visit following the index episode.

In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC \>1 µg/mL.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=233 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=222 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate H flu, nonsusceptible	38 participants	28 participants
The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate H flu, susceptible	39 participants	37 participants
The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate H flu, absent	156 participants	157 participants

SECONDARY outcome

Timeframe: The day 12-14 visit following a recurrence. The mean day for this visit was 13.6.

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible having a NP culture at the day 12-14 visit following an AOM recurrence.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=131 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=99 Recurrences Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate H flu, absent	95 recurrence	64 recurrence
The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate H flu, nonsusceptible	19 recurrence	15 recurrence
The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate H flu, susceptible	17 recurrence	20 recurrence

SECONDARY outcome

Timeframe: Day 1 of study entry until day 60.

Population: The analysis was ITT. The participants are randomized \& eligible children having follow-up greater than or equal to day 60.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=241 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=224 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children With AOM Recurrences and Relapses Within 60 Days of Enrollment # cumulative recurrences/relapses = 0	173 participants	173 participants
The Distribution of Children With AOM Recurrences and Relapses Within 60 Days of Enrollment # cumulative recurrences/relapses = 1	66 participants	48 participants
The Distribution of Children With AOM Recurrences and Relapses Within 60 Days of Enrollment # cumulative recurrences/relapses = 2	2 participants	3 participants

SECONDARY outcome

Timeframe: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.

Population: The analysis was ITT. The participants are randomized \& eligible children completing the study.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=238 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=219 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children With AOM Recurrences and Relapses Within the Entire Respiratory Season # cumulative recurrences/relapses = 0	135 participants	133 participants
The Distribution of Children With AOM Recurrences and Relapses Within the Entire Respiratory Season # cumulative recurrences/relapses = 1	61 participants	59 participants
The Distribution of Children With AOM Recurrences and Relapses Within the Entire Respiratory Season # cumulative recurrences/relapses = 2	31 participants	20 participants
The Distribution of Children With AOM Recurrences and Relapses Within the Entire Respiratory Season # cumulative recurrences/relapses = 3	8 participants	4 participants
The Distribution of Children With AOM Recurrences and Relapses Within the Entire Respiratory Season # cumulative recurrences/relapses = 4	3 participants	3 participants

SECONDARY outcome

Timeframe: Day 1 of study entry until day 60.

Population: The analysis was ITT. The participants are randomized \& eligible children having follow-up beyond day 16.

An episode of AOM occurring after Day 16 will be considered a recurrence. Subjects seen after day 10 and categorized as clinical success who return for an interim/sick visit before day 17 and are found to have AOM will be categorized as a relapse. For secondary outcome analyses, relapses are combined with recurrences. The rate, expressed as a monthly rate, is calculated by dividing the total number of recurrences and relapses within 60 days of enrollment by the number of months of follow-up within 60 days of enrollment.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=245 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=232 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Mean Rate, Per Month, of Protocol AOM Recurrences and Relapses Within 60 Days of Enrollment	0.15 recurrences/relapses per month Standard Deviation 0.24	0.12 recurrences/relapses per month Standard Deviation 0.23

SECONDARY outcome

Timeframe: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.

Population: The analysis was ITT. The participants are randomized \& eligible children having follow-up beyond day 16.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=245 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=232 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Mean Rate, Per Month, of Protocol AOM Recurrences and Relapses Within the Entire Respiratory Season	0.14 recurrences/relapses per months followed Standard Deviation 0.18	0.12 recurrences/relapses per months followed Standard Deviation 0.19

SECONDARY outcome

Timeframe: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible.

Systemic antibiotics include the study product, Amoxicillin-Clavulanate, dispensed for either 10 or 5 days and various concomitant medications, i.e. Amoxicillin, Amox/Clav, Azithromycin, Cefdinir, Cefpodoxime, Ceftriaxone, Erythromycin, Trimethoprim-Sulfamethoxazole, Omnicef, Augmentin, Azithromycin, Cefazolin, Clarythromycin and Ciprofloxacin.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=257 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=258 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Mean Number of Days Systemic Antibiotics Were Received During the Entire Respiratory Season Study product	14.72 days Standard Deviation 6.77	6.79 days Standard Deviation 3.01
The Mean Number of Days Systemic Antibiotics Were Received During the Entire Respiratory Season Other systemic antibiotic	6.19 days Standard Deviation 9.33	7.98 days Standard Deviation 10.94
The Mean Number of Days Systemic Antibiotics Were Received During the Entire Respiratory Season All systemic antibiotics	20.91 days Standard Deviation 12.70	14.77 days Standard Deviation 12.10

SECONDARY outcome

Timeframe: From day 6 of administration of study product until day 14 for all episodes

Population: The analysis was ITT. The number of participants equals the number of children with at least one AOM-SOS score from day 6 of administration of study product to day 14. The scores were based on diaries completed at home by the child's parent.

The AOM-SOS scale measures seven discrete items: tugging of ears, crying, irritability, difficulty sleeping, diminished activity, diminished appetite, and fever. The parent rated each of these symptoms in comparison with the child's usual state, as "none," "a little," or "a lot," with corresponding scores of 0, 1, and 2, and recorded the ratings in a diary. Each set of ratings was summed to obtain an AOM-SOS score as a measure of symptom burden. Total scores range from 0 to 14, with higher scores indicating greater severity of symptoms. For instances in which the participant was declared a treatment failure, scores are included up to, but not including the day of the failure. Otherwise, scores day 6 to day 14 are included.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=234 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=230 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14 Day 6	1.72 AOM-SOS score Standard Deviation 2.14	1.64 AOM-SOS score Standard Deviation 2.38
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14 Day 7	1.46 AOM-SOS score Standard Deviation 2.11	1.57 AOM-SOS score Standard Deviation 2.53
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14 Day 8	1.29 AOM-SOS score Standard Deviation 1.99	1.56 AOM-SOS score Standard Deviation 2.38
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14 Day 9	1.29 AOM-SOS score Standard Deviation 2.10	1.41 AOM-SOS score Standard Deviation 2.22
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14 Day 10	1.12 AOM-SOS score Standard Deviation 1.96	1.43 AOM-SOS score Standard Deviation 2.36
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14 Day 11	1.02 AOM-SOS score Standard Deviation 1.84	1.40 AOM-SOS score Standard Deviation 2.27
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14 Day 12	1.07 AOM-SOS score Standard Deviation 1.83	1.25 AOM-SOS score Standard Deviation 2.12
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14 Day 13	1.15 AOM-SOS score Standard Deviation 1.97	1.40 AOM-SOS score Standard Deviation 2.47
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14 Day 14	1.16 AOM-SOS score Standard Deviation 1.93	1.37 AOM-SOS score Standard Deviation 2.39

SECONDARY outcome

Timeframe: Day 1 of administration of study product until day 16 for all episodes

Population: The analysis was ITT. The number of participants equals the number of children randomized and eligible.

Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=257 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=258 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product PDD reported	78 participants	75 participants
The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product PDD not reported	179 participants	183 participants

SECONDARY outcome

Timeframe: Day 1 of administration of study product until day 16 for all episodes

Population: The analysis was ITT. The number of participants equals the number of children randomized and eligible.

Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product.

Outcome measures

Outcome measures
Measure	Amoxicillin-Clavulanate, 10 Days n=257 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=258 Participants Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
The Distribution of Children for Whom Diaper Dermatitis Was Reported and Associated With Study Product Diaper dermatitis reported	85 participants	87 participants
The Distribution of Children for Whom Diaper Dermatitis Was Reported and Associated With Study Product Diaper dermatitis not reported	172 participants	171 participants

Adverse Events

Amoxicillin-Clavulanate, 10 Days

Serious events: 3 serious events

Other events: 240 other events

Deaths: 0 deaths

Amoxicillin-Clavulanate, 5 Days

Serious events: 5 serious events

Other events: 242 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Amoxicillin-Clavulanate, 10 Days n=257 participants at risk Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=258 participants at risk Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
Gastrointestinal disorders Gastroenteritis	0.39% 1/257 • Number of events 1 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	0.39% 1/258 • Number of events 1 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
General disorders Dehydration	0.00% 0/257 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	0.39% 1/258 • Number of events 1 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
General disorders Fever of unknown origin	0.39% 1/257 • Number of events 1 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	0.00% 0/258 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Infections and infestations Wound infection	0.00% 0/257 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	0.39% 1/258 • Number of events 1 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Nervous system disorders Seizure	0.00% 0/257 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	0.39% 1/258 • Number of events 1 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Respiratory, thoracic and mediastinal disorders Asthma	0.39% 1/257 • Number of events 1 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	0.00% 0/258 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Respiratory, thoracic and mediastinal disorders Bronchiolitis	0.00% 0/257 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	0.39% 1/258 • Number of events 1 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Respiratory, thoracic and mediastinal disorders Croup	0.00% 0/257 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	0.39% 1/258 • Number of events 1 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.

Other adverse events

Other adverse events
Measure	Amoxicillin-Clavulanate, 10 Days n=257 participants at risk Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.	Amoxicillin-Clavulanate, 5 Days n=258 participants at risk Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
Ear and labyrinth disorders Non-protocol acute otitis media (AOM)	17.1% 44/257 • Number of events 48 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	18.6% 48/258 • Number of events 60 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Gastrointestinal disorders Gastroenteritis	11.3% 29/257 • Number of events 31 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	10.5% 27/258 • Number of events 28 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Gastrointestinal disorders Protocol defined diarrhea	32.7% 84/257 • Number of events 112 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	35.3% 91/258 • Number of events 105 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Gastrointestinal disorders Vomiting	21.0% 54/257 • Number of events 62 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	19.8% 51/258 • Number of events 61 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
General disorders Fever	17.1% 44/257 • Number of events 58 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	16.3% 42/258 • Number of events 45 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
General disorders Viral illness	11.7% 30/257 • Number of events 32 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	9.7% 25/258 • Number of events 29 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Infections and infestations Conjunctivitis	14.4% 37/257 • Number of events 40 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	14.0% 36/258 • Number of events 37 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Infections and infestations Sinusitis	4.7% 12/257 • Number of events 12 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	3.1% 8/258 • Number of events 9 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Respiratory, thoracic and mediastinal disorders Bronchospasm, acute	18.7% 48/257 • Number of events 65 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	18.2% 47/258 • Number of events 58 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	76.7% 197/257 • Number of events 469 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	74.0% 191/258 • Number of events 432 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Skin and subcutaneous tissue disorders Diaper dermatitis	64.6% 166/257 • Number of events 300 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	60.1% 155/258 • Number of events 243 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Skin and subcutaneous tissue disorders Rash	10.5% 27/257 • Number of events 30 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	6.6% 17/258 • Number of events 17 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Skin and subcutaneous tissue disorders Viral exanthem	8.2% 21/257 • Number of events 22 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	9.3% 24/258 • Number of events 30 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.
Surgical and medical procedures Tympanostomy tube placement	7.4% 19/257 • Number of events 19 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.	8.5% 22/258 • Number of events 22 • Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events. Staff reviewed child's medical records since their last study visit for any adverse events (AEs). A medical condition that was present at the time that the child was screened was considered baseline and not reported as an AE. If the severity of any pre-existing medical condition increased at any time during the study, it was reported as an AE.

Additional Information

Dr. Alejandro Hoberman

Children's Hospital of Pittsburgh of UPMC

Phone: 412-692-5249

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place