Sinusitis, Respiratory Tract Infections
Conditions
Keywords
pediatrics, antibiotics, placebo
Brief summary
The objective of this trial is to determine whether certain subgroups of children with acute sinusitis exist in whom antibiotic therapy can be appropriately withheld.
Detailed description
The current clinical practice guideline from the American Academy of Pediatrics for the Diagnosis and Management of Acute Bacterial Sinusitis recommends that the diagnosis of acute sinusitis is made when symptoms of an upper respiratory infection (URI) persist beyond 10 days without showing signs of improvement (persistent presentation), when symptoms appear to worsen (on the 6th to 10th day) after a period of improvement (worsening presentation), or when both high fever and purulent nasal discharge are present concurrently for at least 3 consecutive days (severe presentation). In studies to date, children with persistent and worsening presentations comprise \>95% of cases. The investigators preliminary data and the available literature suggest that only a subset of children being diagnosed with acute sinusitis on the basis of current criteria are likely to have bacterial disease. This is not entirely surprising because current criteria rely solely on the duration and the quality of respiratory tract symptoms (which are both common and non-specific). Accordingly, it seems likely that many children currently being diagnosed as having acute sinusitis actually have an uncomplicated upper respiratory infection. This is important because acute sinusitis is one of the most common diagnoses for which antimicrobials are prescribed for children in the United States, accounting for 7.9 million prescriptions annually. A critical need thus exists to establish which subgroups of children currently being diagnosed with acute sinusitis actually benefit from antimicrobial therapy. The objective of this trial is to determine whether certain subgroups of children with acute sinusitis exist in whom antibiotic therapy can be appropriately withheld. This objective will be achieved by conducting a large, randomized, double-blind, placebo-controlled clinical trial in children 2 to 12 years of age with persistent or worsening presentations of acute sinusitis. Based on the investigators preliminary data, the investigators hypothesize that only certain subgroups of children currently being treated for acute sinusitis actually benefit from antimicrobial therapy. By identifying, in a large placebo-controlled trial, subgroups of children who respectively do and do not benefit from antimicrobial therapy, the investigators will be better able to determine which children should be classified as having acute bacterial sinusitis. Accordingly, the results of this trial may impact not only the treatment guidelines for acute sinusitis but also the diagnostic criteria, and will help ensure that, to the extent possible, antibiotic use is limited to appropriate patients. This, in turn, will maximize the likelihood of achieving optimal outcomes and minimize the risk of promoting antibiotic resistance.
Interventions
Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days)
DRUGPlacebo
placebo made to match the study antibiotic given twice a day orally for 10 days
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Nader Shaikh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Meets criteria for persistent or worsening presentations of sinusitis * Baseline score ≥9 on the Pediatric Rhinosinusitis Symptom Scale
Exclusion criteria
* Severe presentation (≥3 days of colored nasal discharge and fever ≥39°C * Asthma/allergic rhinitis explains symptoms * Allergy to amoxicillin-clavulanate * Immotile cilia syndrome * Cystic fibrosis * Immunodeficiency * Parental inability to read/write English or Spanish * Other concurrent infection (e.g., pneumonia, acute otitis media, streptococcal pharyngitis) * Systemic toxicity * Wheezing on exam * Antibiotic use within 15 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Days 2 to 11 | 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. |
| 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 | Days 2 to 11 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up | 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. | 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. |
| The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up | 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. | 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. |
| The Distribution of Children Compliant With Study Medication | Days 1 to 11, where Day 1 is day of enrollment | 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. |
| The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported | Day 1 through Day 23. | 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. |
| The Distribution of Children Experiencing Treatment Failure (TF) | 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. | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit | The follow-up visit. The mean number of days from enrollment to the follow-up visit was 13.4. | 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Amoxicillin-clavulanate Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days) | 254 |
| Placebo Placebo made to match the study antibiotic (will be taken bid orally for 10 days) | 256 |
| Total | 510 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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
| Characteristic | Amoxicillin-clavulanate | Placebo | Total |
|---|---|---|---|
| Age, Customized 2 - 5 years | 159 Participants | 165 Participants | 324 Participants |
| Age, Customized 6 - 12 years | 95 Participants | 91 Participants | 186 Participants |
| Colored Nasal Discharge No | 83 Participants | 87 Participants | 170 Participants |
| Colored Nasal Discharge Yes | 171 Participants | 169 Participants | 340 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 34 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 230 Participants | 222 Participants | 452 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Exposure to Other Children No | 54 Participants | 39 Participants | 93 Participants |
| Exposure to Other Children Yes | 200 Participants | 217 Participants | 417 Participants |
| Fever No | 134 Participants | 120 Participants | 254 Participants |
| Fever Yes | 120 Participants | 136 Participants | 256 Participants |
| History of Allergic Rhinitis No | 176 Participants | 176 Participants | 352 Participants |
| History of Allergic Rhinitis Yes | 78 Participants | 80 Participants | 158 Participants |
| History of Asthma No | 208 Participants | 208 Participants | 416 Participants |
| History of Asthma Yes | 46 Participants | 48 Participants | 94 Participants |
| Pathogens Cultured from Nasopharynx No | 76 Participants | 68 Participants | 144 Participants |
| Pathogens Cultured from Nasopharynx Unknown | 0 Participants | 3 Participants | 3 Participants |
| Pathogens Cultured from Nasopharynx Yes | 178 Participants | 185 Participants | 363 Participants |
| Pediatric Rhinosinusitis Symptom Scale (PRSS) Score 16 -20 | 43 Participants | 49 Participants | 92 Participants |
| Pediatric Rhinosinusitis Symptom Scale (PRSS) Score 21 -25 | 62 Participants | 73 Participants | 135 Participants |
| Pediatric Rhinosinusitis Symptom Scale (PRSS) Score 26 -30 | 65 Participants | 65 Participants | 130 Participants |
| Pediatric Rhinosinusitis Symptom Scale (PRSS) Score 31 -35 | 34 Participants | 34 Participants | 68 Participants |
| Pediatric Rhinosinusitis Symptom Scale (PRSS) Score 36 -40 | 11 Participants | 6 Participants | 17 Participants |
| Pediatric Rhinosinusitis Symptom Scale (PRSS) Score 9 -15 | 39 Participants | 29 Participants | 68 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 91 Participants | 88 Participants | 179 Participants |
| Race (NIH/OMB) More than one race | 24 Participants | 21 Participants | 45 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) White | 128 Participants | 136 Participants | 264 Participants |
| Sex: Female, Male Female | 114 Participants | 122 Participants | 236 Participants |
| Sex: Female, Male Male | 140 Participants | 134 Participants | 274 Participants |
| Study Site Bardstown, KY | 37 Participants | 36 Participants | 73 Participants |
| Study Site Gresham, OR | 2 Participants | 3 Participants | 5 Participants |
| Study Site Madison, WI | 18 Participants | 20 Participants | 38 Participants |
| Study Site Morgantown, WV | 0 Participants | 2 Participants | 2 Participants |
| Study Site Philadelphia, PA | 1 Participants | 1 Participants | 2 Participants |
| Study Site Pittsburgh, PA | 196 Participants | 194 Participants | 390 Participants |
| Type of Presentation Persistent | 180 Participants | 173 Participants | 353 Participants |
| Type of Presentation Worsening | 74 Participants | 83 Participants | 157 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 254 | 0 / 256 |
| other Total, other adverse events | 29 / 254 | 12 / 256 |
| serious Total, serious adverse events | 0 / 254 | 0 / 256 |
Outcome results
Primary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Placebo | 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 | 7.3 Score on a scale | Standard Deviation 6.5 |
| Placebo | 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 | 19.0 Score on a scale | Standard Deviation 7.2 |
| Placebo | 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 | 17.6 Score on a scale | Standard Deviation 8.3 |
| Placebo | 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 | 16.6 Score on a scale | Standard Deviation 7.1 |
| Placebo | 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 | 8.8 Score on a scale | Standard Deviation 6.7 |
| Placebo | 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 | 13.7 Score on a scale | Standard Deviation 7.1 |
| Placebo | 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 | 15.6 Score on a scale | Standard Deviation 7.9 |
| Placebo | 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 | 11.3 Score on a scale | Standard Deviation 6.8 |
| Placebo | 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 | 5.7 Score on a scale | Standard Deviation 6.9 |
| Placebo | 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 | 10.5 Score on a scale | Standard Deviation 6.8 |
| Placebo | 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 | 12.9 Score on a scale | Standard Deviation 8 |
| Placebo | 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 | 8.8 Score on a scale | Standard Deviation 6.4 |
| Placebo | 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 | 7.7 Score on a scale | Standard Deviation 6.5 |
| Placebo | 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 | 8.2 Score on a scale | Standard Deviation 7.1 |
| Placebo | 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 | 12.1 Score on a scale | Standard Deviation 7.1 |
| Placebo | 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 | 7.0 Score on a scale | Standard Deviation 6.7 |
| Placebo | 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 | 6.2 Score on a scale | Standard Deviation 6.4 |
| Placebo | 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 | 5.7 Score on a scale | Standard Deviation 5.9 |
| Placebo | 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 | 10.5 Score on a scale | Standard Deviation 7.3 |
| Placebo | 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 | 5.2 Score on a scale | Standard Deviation 5.9 |
Comparison: Null hypothesis: The effect of treatment with antibiotics does not differ in the subgroups of children defined, respectively, by the presence and by the absence of colored nasal discharge at enrollment, i.e., there is no significant interaction between treatment and colored nasal discharge.p-value: 0.37Mixed Models Analysis
Comparison: Null hypothesis: There is no difference between the treatment groups in the subgroup of children defined by the presence of colored nasal discharge at enrollment.95% CI: [-2.09, -1.16]
Comparison: Null hypothesis: There is no difference between the treatment groups in the subgroup of children defined by the absence of colored nasal discharge at enrollment.95% CI: [-2.38, -1.03]
Primary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Amoxicillin-clavulanate | 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 |
| Placebo | 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 | 5.8 Score on a scale | Standard Deviation 6.5 |
| Placebo | 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 | 8.3 Score on a scale | Standard Deviation 6.7 |
| Placebo | 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 | 8.9 Score on a scale | Standard Deviation 6.4 |
| Placebo | 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 | 7.4 Score on a scale | Standard Deviation 6.8 |
| Placebo | 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 | 18.7 Score on a scale | Standard Deviation 7.2 |
| Placebo | 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 | 6.3 Score on a scale | Standard Deviation 6.7 |
| Placebo | 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 | 8.3 Score on a scale | Standard Deviation 6.9 |
| Placebo | 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 | 5.5 Score on a scale | Standard Deviation 6.5 |
| Placebo | 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 | 9.4 Score on a scale | Standard Deviation 7 |
| Placebo | 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 7.2 |
| Placebo | 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 | 18.6 Score on a scale | Standard Deviation 7.6 |
| Placebo | 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 | 7.4 Score on a scale | Standard Deviation 6.6 |
| Placebo | 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 5.3 |
| Placebo | 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 | 10.5 Score on a scale | Standard Deviation 6.7 |
| Placebo | 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 | 16.6 Score on a scale | Standard Deviation 7.5 |
| Placebo | 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 | 13.9 Score on a scale | Standard Deviation 7.6 |
| Placebo | 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 | 6.0 Score on a scale | Standard Deviation 5.9 |
| Placebo | 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 | 12.0 Score on a scale | Standard Deviation 7 |
| Placebo | 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 | 12.5 Score on a scale | Standard Deviation 6.7 |
| Placebo | 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 | 10.9 Score on a scale | Standard Deviation 6.9 |
Comparison: Null hypothesis: The effect of treatment with antibiotics does not differ in the subgroups of children defined, respectively, by the presence and by the absence of pathogens in the nasopharynx at enrollment, i.e., there is no significant interaction between treatment and pathogens in the nasopharynx.p-value: 0.02Mixed Models Analysis
Comparison: Null hypothesis: There is no difference between the treatment groups in the subgroup of children defined by the presence of one or more pathogens in the nasopharynx at enrollment.95% CI: [-2.4, -1.51]
Comparison: Null hypothesis: There is no difference between the treatment groups in the subgroup of children defined by the absence of one or more pathogens in the nasopharynx at enrollment.95% CI: [-1.63, -0.12]
Secondary
The Distribution of Children Compliant With Study Medication
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate | The Distribution of Children Compliant With Study Medication | Compliant, i.e., received at least 70% of the the study medication | 212 Participants |
| Amoxicillin-clavulanate | The Distribution of Children Compliant With Study Medication | Not compliant, i.e., received less than 70% of study medication | 14 Participants |
| Placebo | The Distribution of Children Compliant With Study Medication | Compliant, i.e., received at least 70% of the the study medication | 221 Participants |
| Placebo | The Distribution of Children Compliant With Study Medication | Not compliant, i.e., received less than 70% of study medication | 13 Participants |
Comparison: Null hypothesis: There is no difference between the treatment groups in the proportion of children compliant with study product.p-value: 0.75Log-binomial regression
Secondary
The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate | The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up | Developed AOM | 0 Participants |
| Amoxicillin-clavulanate | The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up | Did not develop AOM | 251 Participants |
| Placebo | The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up | Developed AOM | 8 Participants |
| Placebo | The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up | Did not develop AOM | 248 Participants |
Comparison: Null hypothesis: There is no difference between the treatment groups in the proportion of children developing AOM over the first 10 days of follow-up.p-value: 0.007Fisher Exact
Secondary
The Distribution of Children Experiencing Treatment Failure (TF)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate | The Distribution of Children Experiencing Treatment Failure (TF) | Experienced failure | 76 Participants |
| Amoxicillin-clavulanate | The Distribution of Children Experiencing Treatment Failure (TF) | Did not experience failure | 178 Participants |
| Placebo | The Distribution of Children Experiencing Treatment Failure (TF) | Experienced failure | 111 Participants |
| Placebo | The Distribution of Children Experiencing Treatment Failure (TF) | Did not experience failure | 145 Participants |
Comparison: Null hypothesis: There is no difference between the treatment groups in the proportion of children experiencing treatment failure.p-value: 0.003Log-binomial regression
Secondary
The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported
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.
Time frame: Day 1 through Day 23.
Population: The analysis was ITT. The number of participants is equal to the number of children randomized \& eligible
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate | The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported | Diarrhea or rash was reported | 31 Participants |
| Amoxicillin-clavulanate | The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported | Neither diarrhea nor rash was reported | 223 Participants |
| Placebo | The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported | Diarrhea or rash was reported | 13 Participants |
| Placebo | The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported | Neither diarrhea nor rash was reported | 243 Participants |
Comparison: Null hypothesis: There is no difference between the treatment groups in the proportion of children for whom diarrhea or generalized rash was reported.p-value: 0.004Log-binomial regression
Secondary
The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate | The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up | Received a systemic antibiotic | 34 Participants |
| Amoxicillin-clavulanate | The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up | Did not receive a systemic antibiotic | 217 Participants |
| Placebo | The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up | Received a systemic antibiotic | 66 Participants |
| Placebo | The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up | Did not receive a systemic antibiotic | 190 Participants |
Comparison: Null hypothesis: There is no difference between the treatment groups in the proportion of children receiving a systemic antibiotic over the first 10 days of follow-up.p-value: <0.001Log-binomial regression
Other Pre-specified
The Distribution of Children With a Nonsusceptible Pathogen at 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.
Time frame: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate | The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit | Nonsusceptible pathogen at the follow-up visit | 19 Participants |
| Amoxicillin-clavulanate | The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit | No nonsusceptible pathogen at the follow-up visit | 129 Participants |
| Placebo | The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit | Nonsusceptible pathogen at the follow-up visit | 18 Participants |
| Placebo | The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit | No nonsusceptible pathogen at the follow-up visit | 134 Participants |
Comparison: Null hypothesis: There is no difference between the treatment groups in the proportion of children with a nonsusceptible pathogen at the follow-up visit.p-value: 0.63Log-binomial regression