Trial Outcomes & Findings for Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit? (NCT NCT02554383)

NCT ID: NCT02554383

Last Updated: 2023-06-29

Results Overview

The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough \& trouble sleeping - as none, almost none, a little, some, a lot \& an extreme amount with respective scores of 0, 1, 2, 3, 4 \& 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment) \& electronically on diaries evenings Days 2-11. Pathogens cultured were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

515 participants

Primary outcome timeframe

Days 2 to 11

Results posted on

2023-06-29

Participant Flow

Children determined to be eligible for the study and whose parents agreed to participation were randomized to one of two treatments arms. At each site of enrollment, within stratum defined by the presence/absence of colored (yellow or green) nasal discharge, children were randomized 1:1 in blocks of four to receive either twice daily amoxicillin-clavulanate or matching placebo. The analyses of study data were based on the randomized treatment assignment.

Participant milestones

Participant milestones
Measure
Amoxicillin-clavulanate
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
Overall Study
STARTED
257
258
Overall Study
COMPLETED
234
239
Overall Study
NOT COMPLETED
23
19

Reasons for withdrawal

Reasons for withdrawal
Measure
Amoxicillin-clavulanate
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
Overall Study
Ineligible
3
2
Overall Study
Parent completed 0 diaries by Day 4 and 0 diaries Days 5-11
8
6
Overall Study
Parent completed 0 diaries by Day 4 and >=1 diary Days 5-11
0
2
Overall Study
Parent completed >=1 diary by Day 4, but <2 diaries Days 2-4 or <3 diaries Days 5-11
12
9

Baseline Characteristics

Efficacy of Antibiotics in Children With Acute Sinusitis: Which Subgroups Benefit?

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Amoxicillin-clavulanate
n=254 Participants
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=256 Participants
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
Total
n=510 Participants
Total of all reporting groups
Age, Customized
2 - 5 years
159 Participants
n=5 Participants
165 Participants
n=7 Participants
324 Participants
n=5 Participants
Age, Customized
6 - 12 years
95 Participants
n=5 Participants
91 Participants
n=7 Participants
186 Participants
n=5 Participants
Sex: Female, Male
Female
114 Participants
n=5 Participants
122 Participants
n=7 Participants
236 Participants
n=5 Participants
Sex: Female, Male
Male
140 Participants
n=5 Participants
134 Participants
n=7 Participants
274 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
24 Participants
n=5 Participants
34 Participants
n=7 Participants
58 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
230 Participants
n=5 Participants
222 Participants
n=7 Participants
452 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
5 Participants
n=5 Participants
5 Participants
n=7 Participants
10 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
91 Participants
n=5 Participants
88 Participants
n=7 Participants
179 Participants
n=5 Participants
Race (NIH/OMB)
White
128 Participants
n=5 Participants
136 Participants
n=7 Participants
264 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
24 Participants
n=5 Participants
21 Participants
n=7 Participants
45 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
5 Participants
n=5 Participants
6 Participants
n=7 Participants
11 Participants
n=5 Participants
Study Site
Pittsburgh, PA
196 Participants
n=5 Participants
194 Participants
n=7 Participants
390 Participants
n=5 Participants
Study Site
Philadelphia, PA
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Study Site
Bardstown, KY
37 Participants
n=5 Participants
36 Participants
n=7 Participants
73 Participants
n=5 Participants
Study Site
Madison, WI
18 Participants
n=5 Participants
20 Participants
n=7 Participants
38 Participants
n=5 Participants
Study Site
Morgantown, WV
0 Participants
n=5 Participants
2 Participants
n=7 Participants
2 Participants
n=5 Participants
Study Site
Gresham, OR
2 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants
History of Asthma
Yes
46 Participants
n=5 Participants
48 Participants
n=7 Participants
94 Participants
n=5 Participants
History of Asthma
No
208 Participants
n=5 Participants
208 Participants
n=7 Participants
416 Participants
n=5 Participants
History of Allergic Rhinitis
Yes
78 Participants
n=5 Participants
80 Participants
n=7 Participants
158 Participants
n=5 Participants
History of Allergic Rhinitis
No
176 Participants
n=5 Participants
176 Participants
n=7 Participants
352 Participants
n=5 Participants
Fever
Yes
120 Participants
n=5 Participants
136 Participants
n=7 Participants
256 Participants
n=5 Participants
Fever
No
134 Participants
n=5 Participants
120 Participants
n=7 Participants
254 Participants
n=5 Participants
Exposure to Other Children
Yes
200 Participants
n=5 Participants
217 Participants
n=7 Participants
417 Participants
n=5 Participants
Exposure to Other Children
No
54 Participants
n=5 Participants
39 Participants
n=7 Participants
93 Participants
n=5 Participants
Type of Presentation
Persistent
180 Participants
n=5 Participants
173 Participants
n=7 Participants
353 Participants
n=5 Participants
Type of Presentation
Worsening
74 Participants
n=5 Participants
83 Participants
n=7 Participants
157 Participants
n=5 Participants
Pediatric Rhinosinusitis Symptom Scale (PRSS) Score
9 -15
39 Participants
n=5 Participants
29 Participants
n=7 Participants
68 Participants
n=5 Participants
Pediatric Rhinosinusitis Symptom Scale (PRSS) Score
16 -20
43 Participants
n=5 Participants
49 Participants
n=7 Participants
92 Participants
n=5 Participants
Pediatric Rhinosinusitis Symptom Scale (PRSS) Score
21 -25
62 Participants
n=5 Participants
73 Participants
n=7 Participants
135 Participants
n=5 Participants
Pediatric Rhinosinusitis Symptom Scale (PRSS) Score
26 -30
65 Participants
n=5 Participants
65 Participants
n=7 Participants
130 Participants
n=5 Participants
Pediatric Rhinosinusitis Symptom Scale (PRSS) Score
31 -35
34 Participants
n=5 Participants
34 Participants
n=7 Participants
68 Participants
n=5 Participants
Pediatric Rhinosinusitis Symptom Scale (PRSS) Score
36 -40
11 Participants
n=5 Participants
6 Participants
n=7 Participants
17 Participants
n=5 Participants
Pathogens Cultured from Nasopharynx
Yes
178 Participants
n=5 Participants
185 Participants
n=7 Participants
363 Participants
n=5 Participants
Pathogens Cultured from Nasopharynx
No
76 Participants
n=5 Participants
68 Participants
n=7 Participants
144 Participants
n=5 Participants
Pathogens Cultured from Nasopharynx
Unknown
0 Participants
n=5 Participants
3 Participants
n=7 Participants
3 Participants
n=5 Participants
Colored Nasal Discharge
Yes
171 Participants
n=5 Participants
169 Participants
n=7 Participants
340 Participants
n=5 Participants
Colored Nasal Discharge
No
83 Participants
n=5 Participants
87 Participants
n=7 Participants
170 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Days 2 to 11

Population: The analysis was intention-to-treat (ITT). The overall number of participants analyzed is equal to the number of children randomized \& eligible who had results of a nasopharyngeal culture at enrollment and whose parent completed the PRSS at least once Days 2 to 11. For any given day, the total number analyzed plus the total number without diary data available on that day is equal to the overall number of participants analyzed for the respective Arm/Group.

The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough \& trouble sleeping - as none, almost none, a little, some, a lot \& an extreme amount with respective scores of 0, 1, 2, 3, 4 \& 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment) \& electronically on diaries evenings Days 2-11. Pathogens cultured were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

Outcome measures

Outcome measures
Measure
Amoxicillin-clavulanate
n=246 Participants
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=247 Participants
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 2
17.3 Score on a scale
Standard Deviation 7.8
18.6 Score on a scale
Standard Deviation 7.6
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 3
13.9 Score on a scale
Standard Deviation 7.7
16.6 Score on a scale
Standard Deviation 7.5
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 4
11.8 Score on a scale
Standard Deviation 7.9
13.9 Score on a scale
Standard Deviation 7.6
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 5
10.1 Score on a scale
Standard Deviation 7.6
12.0 Score on a scale
Standard Deviation 7.0
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 6
8.5 Score on a scale
Standard Deviation 7.1
10.9 Score on a scale
Standard Deviation 6.9
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 7
7.3 Score on a scale
Standard Deviation 6.7
8.9 Score on a scale
Standard Deviation 6.4
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 8
6.4 Score on a scale
Standard Deviation 6.7
8.3 Score on a scale
Standard Deviation 6.9
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 9
4.9 Score on a scale
Standard Deviation 5.8
7.4 Score on a scale
Standard Deviation 6.6
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 10
4.2 Score on a scale
Standard Deviation 5.4
6.0 Score on a scale
Standard Deviation 5.9
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Presence of 1 or more pathogens in the nasopharynx at enrollment - Day 11
3.7 Score on a scale
Standard Deviation 5.1
5.8 Score on a scale
Standard Deviation 6.5
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 2
19.5 Score on a scale
Standard Deviation 7.3
18.7 Score on a scale
Standard Deviation 7.2
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 3
15.5 Score on a scale
Standard Deviation 8.1
15.5 Score on a scale
Standard Deviation 7.2
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 4
11.9 Score on a scale
Standard Deviation 7.4
12.5 Score on a scale
Standard Deviation 6.7
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 5
10.3 Score on a scale
Standard Deviation 7.4
10.5 Score on a scale
Standard Deviation 6.7
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 6
8.1 Score on a scale
Standard Deviation 7.1
9.4 Score on a scale
Standard Deviation 7.0
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 7
6.9 Score on a scale
Standard Deviation 6.5
8.3 Score on a scale
Standard Deviation 6.7
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 8
6.2 Score on a scale
Standard Deviation 6.4
7.4 Score on a scale
Standard Deviation 6.8
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 9
5.4 Score on a scale
Standard Deviation 6.1
6.3 Score on a scale
Standard Deviation 6.7
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 10
4.9 Score on a scale
Standard Deviation 5.9
5.5 Score on a scale
Standard Deviation 6.5
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment
Absence of 1 or more pathogens in the nasopharynx at enrollment - Day 11
4.1 Score on a scale
Standard Deviation 5.5
4.1 Score on a scale
Standard Deviation 5.3

PRIMARY outcome

Timeframe: Days 2 to 11

Population: The analysis was ITT. The overall number of participants analyzed is equal to the number of children randomized \& eligible whose parent completed the PRSS at least once Days 2 to 11. For any given day, the total number analyzed plus the total number without diary data available on that day is equal to the overall number of participants analyzed for the respective Arm/Group.

The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough \& trouble sleeping - as none, almost none, a little, some, a lot \& an extreme amount with respective scores of 0, 1, 2, 3, 4 \& 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment) \& electronically on diaries evenings Days 2-11. Nasal discharge, either yellow or green, was considered colored.

Outcome measures

Outcome measures
Measure
Amoxicillin-clavulanate
n=246 Participants
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=250 Participants
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 2
18.6 Score on a scale
Standard Deviation 7.9
19.0 Score on a scale
Standard Deviation 7.2
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 3
14.8 Score on a scale
Standard Deviation 8.3
16.6 Score on a scale
Standard Deviation 7.1
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 4
12.1 Score on a scale
Standard Deviation 8.1
13.7 Score on a scale
Standard Deviation 7.1
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 5
10.8 Score on a scale
Standard Deviation 7.8
11.3 Score on a scale
Standard Deviation 6.8
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 6
8.6 Score on a scale
Standard Deviation 7.1
10.5 Score on a scale
Standard Deviation 6.8
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 7
7.4 Score on a scale
Standard Deviation 6.8
8.8 Score on a scale
Standard Deviation 6.4
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 8
6.4 Score on a scale
Standard Deviation 6.4
8.2 Score on a scale
Standard Deviation 7.1
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 9
5.1 Score on a scale
Standard Deviation 6.1
7.0 Score on a scale
Standard Deviation 6.7
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 10
4.4 Score on a scale
Standard Deviation 5.5
5.7 Score on a scale
Standard Deviation 5.9
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Presence of colored nasal discharge at enrollment - Day 11
3.7 Score on a scale
Standard Deviation 5.2
5.2 Score on a scale
Standard Deviation 5.9
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 2
16.4 Score on a scale
Standard Deviation 7.1
17.6 Score on a scale
Standard Deviation 8.3
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 3
13.3 Score on a scale
Standard Deviation 6.8
15.6 Score on a scale
Standard Deviation 7.9
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 4
11.1 Score on a scale
Standard Deviation 7.0
12.9 Score on a scale
Standard Deviation 8.0
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 5
9.0 Score on a scale
Standard Deviation 6.8
12.1 Score on a scale
Standard Deviation 7.1
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 6
7.8 Score on a scale
Standard Deviation 7.1
10.5 Score on a scale
Standard Deviation 7.3
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 7
6.7 Score on a scale
Standard Deviation 6.3
8.8 Score on a scale
Standard Deviation 6.7
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 8
6.1 Score on a scale
Standard Deviation 6.9
7.7 Score on a scale
Standard Deviation 6.5
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 9
4.9 Score on a scale
Standard Deviation 5.5
7.3 Score on a scale
Standard Deviation 6.5
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 10
4.5 Score on a scale
Standard Deviation 5.6
6.2 Score on a scale
Standard Deviation 6.4
The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment
Absence of colored nasal discharge at enrollment - Day 11
4.0 Score on a scale
Standard Deviation 5.2
5.7 Score on a scale
Standard Deviation 6.9

SECONDARY outcome

Timeframe: Day of enrollment to the day of the follow-up visit. The mean length of actual follow-up was 13.4 days. For each child with incomplete follow-up, multiple imputation was used and PRSS scores for the remaining days were imputed.

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

The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough \& trouble sleeping - as none, almost none, a little, some, a lot \& an extreme amount with respective scores of 0, 1, 2, 3, 4 \& 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment), electronically evenings Days 2-11 \& at the follow-up visit. If, compared to the Day 1 score, there was \>20% increase at any time, decrease \<2 on Day 3, \<20% decrease on Day 4, \<20% decrease on 2 consecutive occasions Days 5-11 or \<50% decrease at follow-up, then criterion for treatment failure (TF) was met. Multiple imputation was used when data was insufficient to assess TF.

Outcome measures

Outcome measures
Measure
Amoxicillin-clavulanate
n=254 Participants
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=256 Participants
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
The Distribution of Children Experiencing Treatment Failure (TF)
Experienced failure
76 Participants
111 Participants
The Distribution of Children Experiencing Treatment Failure (TF)
Did not experience failure
178 Participants
145 Participants

SECONDARY outcome

Timeframe: Days 2 to 11, where Day 1 is day of enrollment. The mean number of days of follow-up in this interval was 9.8.

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible with follow-up post-enrollment.

AOM is an infection of the middle ear marked by acute symptoms and a bulging tympanic membrane. Its diagnosis coincided with receipt of a systemic antibiotic. Systemic antibiotics include Amoxicillin, Amoxicillin-clavulanate, Azithromycin, Bacillin L-A, Cefdinir, Clindamycin, Doxycycline, Levofloxacin, Ofloxacin \& Sulfamethoxazole-Trimethoprim. Start and stop dates were recorded.

Outcome measures

Outcome measures
Measure
Amoxicillin-clavulanate
n=251 Participants
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=256 Participants
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up
Developed AOM
0 Participants
8 Participants
The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up
Did not develop AOM
251 Participants
248 Participants

SECONDARY outcome

Timeframe: Days 2 to 11, where Day 1 is day of enrollment. The mean number of days of follow-up in this interval was 9.8.

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible with follow-up post-enrollment.

Systemic antibiotics include Amoxicillin, Amoxicillin-clavulanate, Azithromycin, Bacillin L-A, Cefdinir, Clindamycin, Doxycycline, Levofloxacin, Ofloxacin \& Sulfamethoxazole-Trimethoprim. Start and stop dates were recorded. The antibiotic received is exclusive of the study product assigned at enrollment.

Outcome measures

Outcome measures
Measure
Amoxicillin-clavulanate
n=251 Participants
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=256 Participants
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up
Received a systemic antibiotic
34 Participants
66 Participants
The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up
Did not receive a systemic antibiotic
217 Participants
190 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 23.

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

The monitoring of adverse events (AEs), i.e. diarrhea or generalized rash, began on Day 1 (enrollment) and continued through Day 23 (the follow-up visit). Diarrhea was the occurrence of 3 or more watery stools on one day or 2 watery stools on each of 2 consecutive days. Parents recorded in daily diaries, Days 1-11, information regarding the occurrence of diarrhea. Additionally, parents were asked at the follow-up visit if their child had diarrhea while on study product.

Outcome measures

Outcome measures
Measure
Amoxicillin-clavulanate
n=254 Participants
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=256 Participants
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported
Diarrhea or rash was reported
31 Participants
13 Participants
The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported
Neither diarrhea nor rash was reported
223 Participants
243 Participants

SECONDARY outcome

Timeframe: Days 1 to 11, where Day 1 is day of enrollment

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible with information sufficient to determine compliance.

Compliance, expressed as a percentage, is the total number of doses taken divided by the total number of expected doses. The child is considered compliant if he/she has received at least 70% of the study medication. The parent completed diaries evenings Days 2-11. The diaries included yes/no questions - (1) did your child take the study medication last night and (2) did your child take the study medication this morning? The total number of doses taken was calculated based on the responses to question (1), and accounted for the dose dispensed at enrollment when enrollment was 1pm or earlier on Day 1. The total of expected doses was determined from the responses to questions (1) and (2), and accounted for scenarios in which the child was taken off the study medication by the clinician. In some cases, due to incomplete diaries the information was insufficient to declare a child either compliant or not compliant.

Outcome measures

Outcome measures
Measure
Amoxicillin-clavulanate
n=226 Participants
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=234 Participants
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
The Distribution of Children Compliant With Study Medication
Compliant, i.e., received at least 70% of the the study medication
212 Participants
221 Participants
The Distribution of Children Compliant With Study Medication
Not compliant, i.e., received less than 70% of study medication
14 Participants
13 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: The follow-up visit. The mean number of days from enrollment to the follow-up visit was 13.4.

Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible with a nasopharyngeal specimen obtained at the time of the follow-up visit

The nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (SPN) and ß-lactamase-positive Haemophilus influenzae (NTHi). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<=0.06 μg/mL; intermediate as an MIC of greater than 0.06 to less than 2 μg/mL; and resistant as an MIC of \>=2 μg/mL. A nasopharyngeal specimen for bacterial culture was obtained at the time of the follow-up visit, occurring between study days 11 and 23.

Outcome measures

Outcome measures
Measure
Amoxicillin-clavulanate
n=148 Participants
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=152 Participants
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit
Nonsusceptible pathogen at the follow-up visit
19 Participants
18 Participants
The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit
No nonsusceptible pathogen at the follow-up visit
129 Participants
134 Participants

Adverse Events

Amoxicillin-clavulanate

Serious events: 0 serious events
Other events: 29 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Amoxicillin-clavulanate
n=254 participants at risk
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
Placebo
n=256 participants at risk
Placebo made to match the study antibiotic (will be taken bid orally for 10 days)
Gastrointestinal disorders
Diarrhea
11.4%
29/254 • Number of events 31 • The monitoring of adverse events (AEs) began on Day 1 (enrollment) and continued through Day 23 (the follow-up visit). All recorded AEs were followed to adequate resolution.
Parents recorded in daily diaries, Days 1-11, information regarding the occurrence of diarrhea. Additionally, parents were asked at the follow-up visit if their child had diarrhea while on study product.
4.7%
12/256 • Number of events 13 • The monitoring of adverse events (AEs) began on Day 1 (enrollment) and continued through Day 23 (the follow-up visit). All recorded AEs were followed to adequate resolution.
Parents recorded in daily diaries, Days 1-11, information regarding the occurrence of diarrhea. Additionally, parents were asked at the follow-up visit if their child had diarrhea while on study product.

Additional Information

Nader Shaikh

University of Pittsburgh

Phone: 412-692-8111

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place