Acute Otitis Media
Conditions
Keywords
acute otitis media, infants, children
Brief summary
The purpose of this study is to learn whether or not all children with ear infections (acute otitis media or AOM) should be treated with antibiotics. The study will compare two treatment strategies, watchful waiting or treatment with antibiotics, to determine which is more appropriate for children with AOM. About 268 children in Pittsburgh, between the ages of 6-23 months, with AOM will be enrolled in the study. They will be treated either with Augmentin (an antibiotic) or placebo for 10 days and closely followed for about 1 month. Parents will be asked to write information about their child in a Patient Diary. A general physical exam, including an ear exam, will be performed 4 times during the study. A mucus sample will be collected from the back of each child's nose. Parents will be asked questions during phone calls and at every visit. If a child has not improved or has worsened, the investigators will prescribe a different antibiotic that is known to kill resistant germs.
Detailed description
The purpose of this randomized, double-masked, placebo-controlled, single-center clinical trial is to determine the efficacy of antimicrobials in young children with acute otitis media (AOM). The primary objectives are to compare time to resolution of symptoms (initial and sustained) in children receiving amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses for 10 days) to children receiving placebo (in 2 divided doses for 10 days), and to compare the weighted average AOM-Severity of Symptoms (AOM-SOS) scores in the two groups during days 1-7. The secondary objectives are to: evaluate the clinical efficacy of amoxicillin-clavulanate vs. placebo at the on-therapy visit (Day 4-5, and at least 72 hours after initial dose of study medication); evaluate the clinical efficacy of amoxicillin-clavulanate vs. placebo at the end-of-therapy visit (Day 10-12); compare AOM-SOS and AOM-Faces scales between treatment groups during each of the first 7 days of therapy and at all study visits; compare the proportion of children in each treatment group who develop worsening symptoms before having received 72 hours of study medication; compare the two treatment groups regarding the quantity of analgesic medication administered by children's parents; compare the incidence of adverse events accompanying the two treatment regimens; compare the effects of amoxicillin-clavulanate vs. placebo on the overall proportion of children with nasopharyngeal (NP) colonization with AOM pathogens (S. pneumoniae, H. influenzae, M. catarrhalis, S. pyogenes), and on the proportion of children with NP colonization with penicillin non-susceptible S. pneumoniae; compare the 2 treatment groups regarding tympanometric outcomes at the on-therapy (Day 4-5), end-of-therapy (Day 10-12) and follow-up (Day 21-25) visits, using an algorithm that permits estimation of the probability of middle ear effusion given any particular tympanographic configuration; compare direct and indirect medical costs between the two treatment groups; and compare parental satisfaction with therapy between the two treatment groups. Participants will include 268 children, aged 6 to 23 months, diagnosed with acute otitis media in Western Pennsylvania. These participants will be recruited into the study at Children's Hospital of Pittsburgh (CHP), Pittsburgh, PA, and Armstrong Pediatrics (Children's Community Pediatrics: an affiliate of CHP) in Kittanning, PA. Subjects will be randomized to receive either amoxicillin-clavulanate or placebo twice daily for 10 days. Parents of the subject will be asked to track symptom status, medication use (study medication and acetaminophen), fever and diarrhea in a study memory aid. Study procedures will include a medical history, vital signs, weight, clinical information regarding signs and symptoms of infection, nasopharyngeal specimens, and a physical exam including tympanometry. Each child will be examined three additional times: 4-5 days after starting the medicine, study day 10-12 and 21-25 days after enrolling in the study. During these visits, study staff will review the child's symptoms and examine the child's ears. The study staff will also obtain a nasopharyngeal culture in order to look for resistant bacteria and to make appropriate changes in antibiotic treatment. Daily telephone assessments will be made by study staff on days 2, 3, and 4 of therapy to make sure the child is getting better. The study staff will see a child anytime a parent feels their child has not improved or has worsened.
Interventions
Augmentin ES-600™: Amoxicillin-clavulanate potassium (600/42.9 mg per 5 mL), administered at a dose of 90/6.4 mg/kg/day in 2 divided doses for 10 days with strawberry cream flavor.
DRUGPlacebo
Same base formulation of the licensed product Augmentin ES-600™, with the same strawberry cream flavor.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to 23 Months
Healthy volunteers
No
Inclusion criteria
* aged 6 to 23 months * have received at least two doses of pneumococcal conjugate vaccine (Prevnar) and Haemophilus influenzae type B vaccine * have evidence of acute otitis media (AOM) defined as: 1. Recent (within 48 hours), onset of signs and symptoms and a score of greater than or equal to 3 on the AOM-SOS scale. 2. Middle ear effusion evidenced by at least two of the following: * decreased or absent tympanic membrane mobility by pneumatic otoscopy, * yellow or white discoloration of the tympanic membrane, * opacification of the tympanic membrane, plus * 1+ bulging of the tympanic membrane with either marked erythema or otalgia, or * 2+ or 3+ bulging of the tympanic membrane
Exclusion criteria
* certain signs or symptoms (e.g., toxic appearance \[capillary refill greater than 3 seconds, systolic blood pressure less than 60 mm Hg\], otalgia for a period greater than 48 hours, spontaneous perforation of the tympanic membrane and drainage or temperature greater than or equal to 105 degrees F); * clinical or anatomical characteristics that might obscure response to treatment (e.g., tympanostomy tube\[s\] in place or a history of tympanostomy tubes, unrepaired or repaired overt or submucous cleft palate, high-arched palate, or Down's syndrome); * underlying systemic problems that might obscure response to infection (e.g., serious underlying disease \[e.g., cystic fibrosis, neoplasm, juvenile diabetes\]), concomitant infection that would preclude evaluation of the response of the child's AOM to study medication, known renal insufficiency (i.e., serum creatinine greater than or equal to 1.5 times upper limit of normal for age), known hepatic insufficiency or a history of amoxicillin-clavulanate-associated cholestatic jaundice or hepatic dysfunction, history of immune dysfunction, deficiency or receipt of immunosuppressive therapy, chronic gastrointestinal conditions (i.e., malabsorption, inflammatory bowel disease), malignancy; * sensorineural hearing loss either unilateral or bilateral; * comedications (e.g., systemic corticosteroids at any point while enrolled in the study, more than one dose of systemic antimicrobial therapy within 96, any investigational drug or vaccine; * hypersensitivity to penicillin, amoxicillin or amoxicillin-clavulanate, or phenylketonuria or known hypersensitivity to aspartame; * unable to complete the study protocol or not having access to a telephone; and * current enrollment in another study or previously enrolled in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | The first 7 days on therapy | Time to resolution of symptoms is defined as the time from randomization until a child's AOM-SOS score reaches 0 or 1. The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 and 3, then once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score. The maximum possible score was 14 and the minimum was 0. A score \>=3 was required to be enrolled in the study. |
| The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | The first 7 days on therapy | Time to resolution of symptoms is defined as the time from randomization until a child's AOM-SOS score reaches \<= 1 on two consecutive occasions. The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) & recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 & 3, & once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score. The maximum possible was 14 and the minimum 0. A score \>=3 was required to be enrolled in the study. |
| The Weighted Average Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, According to Treatment Assignment | During the first 7 days of therapy | The AOM-SOS score is derived from parent scoring each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) associated with AOM as 0, 1 or 2 (none, a little, a lot). The AOM-SOS was administered twice daily the first 3 days of follow-up, then daily for 4 additional days. Symptom burden for each child is determined by calculating the weighted average of symptom scores post-enrollment over the first 7 days of therapy. Scores are weighted by 1/k, where k is the number of post-enrollment assessments taken on that day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Distribution of Children Developing Worsening Symptoms Prior to Receiving 72 Hours of Study Medication According to Treatment Assignment | Before receiving 72 hours of study medication | The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1 and twice daily Days 2 and 3. Each set of ratings was summed to obtain an Acute Otitis Media-Severity of Symptoms (AOM-SOS) score. We compared a child's AOM-SOS scores in the first 72 hours to his/her score at enrollment to determine if a child's symptoms got worse (score increased) or remained unchanged or improved (score remained same or decreased). |
| The Mean Number of Times Analgesic Medication Was Administered to the Child According to Treatment Assignment | The first 10 days of follow-up | The parents were asked to complete a memory aid for the first 10 days of the study. One item asked them to record medications administered to the child in addition to the study medication. The data presented shows the mean number of times analgesic, i.e. ibuprofen or acetaminophen, was administered. |
| The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | We monitored children and queried parents regarding adverse events at each study visit, i.e. Day 4-5, Day 10-12, and Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this visit was 22.8. | Analysis was limited to those adverse events identified as being associated with either the study medication or the antimicrobials administered to children who were treatment failures or as being a complication of acute otitis media. |
| The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | End-of-therapy visit. The mean day for this visit was 11.6. | AOM pathogens are defined as Streptococcus Pneumoniae or Haemophilus Influenzae or Moraxella Catarrhalis or Streptococcus Pyogenes. Nasopharyngeal cultures were obtained at the end of therapy visit. |
| The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the End-of-therapy Visit According to Treatment Assignment | End-of-therapy visit. The mean day for this visit was 11.6. | — |
| The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Follow-up visit. The mean day for this visit was 22.8. | AOM pathogens are defined as Streptococcus Pneumoniae or Haemophilus Influenzae or Moraxella Catarrhalis or Streptococcus Pyogenes. Nasopharyngeal cultures were obtained at the follow-up visit. |
| The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the Follow-up Visit | Follow-up visit. The mean day for this visit was 22.8. | — |
| The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the On-therapy Visit According to Treatment Assignment | On-therapy visit. The mean day for this visit was 5.0. | For tympanograms with values for height, middle-ear air pressure, and gradient width, the probability of Middle Ear Effusion (MEE) was estimated by applying an algorithm developed by Smith et al. If the tympanogram was flat and had no printed values for the 3 fields, the probability of MEE was estimated to be .802 based on the proportion of ears with flat graphs that were found otoscopically, by Smith et al, to have MEE. |
| The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the End-of-therapy Visit According to Treatment Assignment | End-of-therapy visit. The mean day for this visit was 11.6. | For tympanograms with values for height, middle-ear air pressure, and gradient width, the probability of Middle Ear Effusion (MEE) was estimated by applying an algorithm developed by Smith et al. If the tympanogram was flat and had no printed values for the 3 fields, the probability of MEE was estimated to be .802 based on the proportion of ears with flat graphs that were found otoscopically, by Smith et al, to have MEE. |
| The Distribution of Clinical Failures by the On-therapy Visit According to Treatment Assignment | On-therapy visit. The mean day for this visit was 5.0. | Clinical failure by the on-therapy visit is defined as either failure to achieve substantial improvement in symptoms, or worsening of otoscopic signs, or both. |
| The Mean Number of Visits to a Primary Care Provider (PCP) According to Treatment Assignment | This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8. | At each visit parents were asked if they had taken their child to his/her primary care physician since the last contact. Medical records were also reviewed. |
| The Mean Number of Emergency Room Visits According to Treatment Assignment | This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8. | At each visit we asked parents if they had to take their child to the emergency department. We also reviewed medical records to assure even more accurate reporting. |
| The Mean Number of Antibiotic Prescriptions, Exclusive of Study Medication, According to Treatment Assignment | This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8. | This is the number of times, in the course of the study, a child required treatment with an antibiotic other than the blinded study medication. |
| The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Having Missed Work According to Treatment Assignment | This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8. | At each visit, parent or parents were asked if their child's illness had caused either parent to miss a day or partial day of work. The total number of visits is summed across all participants in the respective treatment arms. |
| The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Making Special Daycare Arrangements According to Treatment Assignment | This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8. | At each visit, parent or parents were asked if their child's illness had caused them to make alternative daycare arrangements. The total number of visits is summed across all participants in the respective treatment arms. |
| The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the On-therapy Visit According to Treatment Assignment | On-therapy visit. The mean day for this visit was 5.0. | Parents were asked to circle the expression that best represented their satisfaction with the study medication. These expressions have an assigned value: Very dissatisfied = 1, Somewhat dissatisfied = 2, Neither satisfied nor dissatisfied = 3, Somewhat satisfied = 4 and Very satisfied = 5. |
| The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the End-of-therapy Visit According to Treatment Assignment | End-of-therapy visit. The mean day for this visit was 11.6. | Parents were asked to circle the expression that best represented their satisfaction with the study medication. These expressions have an assigned value: Very dissatisfied = 1, Somewhat dissatisfied = 2, Neither satisfied nor dissatisfied = 3, Somewhat satisfied = 4 and Very satisfied = 5. |
| The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment | Follow-up visit. The mean day for this visit was 22.8. | Parents were asked to circle the expression that best represented their satisfaction with the study medication. These expressions have an assigned value: Very dissatisfied = 1, Somewhat dissatisfied = 2, Neither satisfied nor dissatisfied = 3, Somewhat satisfied = 4 and Very satisfied = 5. |
| The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the Follow-up Visit According to Treatment Assignment | Follow-up visit. The mean day for this visit was 22.8. | For tympanograms with values for height, middle-ear air pressure, and gradient width, the probability of Middle Ear Effusion (MEE) was estimated by applying an algorithm developed by Smith et al. If the tympanogram was flat and had no printed values for the 3 fields, the probability of MEE was estimated to be .802 based on the proportion of ears with flat graphs that were found otoscopically, by Smith et al, to have MEE. |
| The Distribution of Clinical Failures by the End-of-therapy Visit According to Treatment Assignment | End-of-therapy visit. The mean day for this visit was 11.6. | Clinical failure by the end of therapy visit is defined as failure to achieve complete or virtually complete resolution of symptoms and of otoscopic signs, but without regard to the persistence of middle ear effusion. |
| The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | During the first 7 days of therapy | The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 and 3, then once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score as a measure of symptom burden. The maximum possible score was 14 and the minimum was 0. |
Countries
United States
Participant flow
Recruitment details
Children were recruited over 3 respiratory seasons, beginning on 11/31/2006 with the last enrollment on 3/31/2009. There were 2 enrollment sites, as well as referrals from private pediatricians. One site was a large private practice; the other was a large hospital based practice. This was for generalizability.
Pre-assignment details
There were 2 children who signed consents but were not randomized. One parent withdrew consent and one child, referred from an outside practice, was found to not be eligible.
Participants by arm
| Arm | Count |
|---|---|
| Amoxicillin-Clavulanate Reconstituted amoxicillin-clavulanate at 90/6.4 mg/kg/day in 2 divided doses for 10 days. | 144 |
| Placebo Reconstituted placebo in 2 divided doses for 10 days. | 147 |
| Total | 291 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Amoxicillin-Clavulanate | Placebo | Total |
|---|---|---|---|
| Age, Customized 12-17 months | 35 participants | 42 participants | 77 participants |
| Age, Customized 18-23 months | 26 participants | 27 participants | 53 participants |
| Age, Customized 6-11 months | 83 participants | 78 participants | 161 participants |
| Colonization With AOM Pathogens Absence of any AOM pathogen | 16 participants | 24 participants | 40 participants |
| Colonization With AOM Pathogens No culture result | 5 participants | 4 participants | 9 participants |
| Colonization With AOM Pathogens Presence of at least one AOM pathogen | 123 participants | 119 participants | 242 participants |
| Degree of tympanic membrane bulging Marked | 39 participants | 38 participants | 77 participants |
| Degree of tympanic membrane bulging Moderate | 63 participants | 70 participants | 133 participants |
| Degree of tympanic membrane bulging Slight | 42 participants | 39 participants | 81 participants |
| Ethnicity Hispanic | 21 participants | 19 participants | 40 participants |
| Ethnicity Non-Hispanic | 123 participants | 128 participants | 251 participants |
| Exposed to other children Exposed | 69 participants | 72 participants | 141 participants |
| Exposed to other children Not exposed | 75 participants | 75 participants | 150 participants |
| Gender Female | 69 Participants | 67 Participants | 136 Participants |
| Gender Male | 75 Participants | 80 Participants | 155 Participants |
| Health insurance status Medicaid | 98 participants | 103 participants | 201 participants |
| Health insurance status None | 3 participants | 2 participants | 5 participants |
| Health insurance status Private | 43 participants | 42 participants | 85 participants |
| History of recurrent acute otitis media No | 123 participants | 118 participants | 241 participants |
| History of recurrent acute otitis media Yes | 21 participants | 29 participants | 50 participants |
| Laterality of Acute Otitis Media Bilateral | 75 participants | 77 participants | 152 participants |
| Laterality of Acute Otitis Media Unilateral | 69 participants | 70 participants | 139 participants |
| Maternal Education College graduate | 30 participants | 35 participants | 65 participants |
| Maternal Education High school graduate | 90 participants | 95 participants | 185 participants |
| Maternal Education Less than high school | 24 participants | 16 participants | 40 participants |
| Maternal Education Unknown | 0 participants | 1 participants | 1 participants |
| Mean Estimated Probability of Middle Ear Effusion Left ear | .35 probability of effusion STANDARD_DEVIATION 0.3 | .44 probability of effusion STANDARD_DEVIATION 0.29 | .40 probability of effusion STANDARD_DEVIATION 0.3 |
| Mean Estimated Probability of Middle Ear Effusion Right ear | .42 probability of effusion STANDARD_DEVIATION 0.31 | .39 probability of effusion STANDARD_DEVIATION 0.27 | .41 probability of effusion STANDARD_DEVIATION 0.29 |
| Mean score of AOM-SOS | 7.69 AOM-SOS score STANDARD_DEVIATION 2.85 | 7.90 AOM-SOS score STANDARD_DEVIATION 2.87 | 7.80 AOM-SOS score STANDARD_DEVIATION 2.86 |
| Race African-American | 62 participants | 58 participants | 120 participants |
| Race Caucasian | 66 participants | 65 participants | 131 participants |
| Race Other | 16 participants | 24 participants | 40 participants |
| Severity of symptoms score Score of 12-14 | 15 participants | 19 participants | 34 participants |
| Severity of symptoms score Score of 3-5 | 37 participants | 33 participants | 70 participants |
| Severity of symptoms score Score of 6-8 | 46 participants | 51 participants | 97 participants |
| Severity of symptoms score Score of 9-11 | 46 participants | 44 participants | 90 participants |
| Study Site Armstrong Pediatrics (Kittanning, PA) | 31 participants | 30 participants | 61 participants |
| Study Site Children's Hospital of Pittsburgh (Pittsburgh, PA) | 113 participants | 117 participants | 230 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 117 / 144 | 104 / 147 |
| serious Total, serious adverse events | 0 / 144 | 2 / 147 |
Outcome results
Primary
The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment
Time to resolution of symptoms is defined as the time from randomization until a child's AOM-SOS score reaches 0 or 1. The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 and 3, then once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score. The maximum possible score was 14 and the minimum was 0. A score \>=3 was required to be enrolled in the study.
Time frame: The first 7 days on therapy
Population: The analysis was ITT. The number of participants is equal to the number of children randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 1 - PM | 20 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 1 - PM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 2 - AM | 38 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 2 - AM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 2 - PM | 50 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 2 - PM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 3 - AM | 70 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 3 - AM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 3 - PM | 77 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 3 - PM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 4 | 87 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 4 | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 5 | 96 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 5 | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 6 | 110 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 6 | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 7 | 114 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 7 | 30 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 5 | 4 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 1 - PM | 9 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 3 - PM | 4 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 1 - PM | 2 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 7 | 41 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 2 - AM | 28 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 4 | 78 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 2 - AM | 2 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 6 | 98 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 2 - PM | 41 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 4 | 4 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 2 - PM | 3 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 7 | 106 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 3 - AM | 58 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 5 | 92 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 3 - AM | 3 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Censored by Day 6 | 4 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment | Resolved by Day 3 - PM | 66 participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the time to resolution of symptoms where resolution is defined as AOM-SOS score \<=1.p-value: 0.14Regression, Cox
Primary
The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment
Time to resolution of symptoms is defined as the time from randomization until a child's AOM-SOS score reaches \<= 1 on two consecutive occasions. The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) & recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 & 3, & once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score. The maximum possible was 14 and the minimum 0. A score \>=3 was required to be enrolled in the study.
Time frame: The first 7 days on therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 1 - PM | 0 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 1 - PM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 2 - AM | 17 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 2 - AM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 2 - PM | 29 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 2 - PM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 3 - AM | 34 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 3 - AM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 3 - PM | 50 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 3 - PM | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 4 | 58 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 4 | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 5 | 70 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 5 | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 6 | 80 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 6 | 1 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 7 | 96 participants |
| Amoxicillin-Clavulanate | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 7 | 48 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 5 | 5 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 1 - PM | 0 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 3 - PM | 4 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 1 - PM | 2 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 7 | 71 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 2 - AM | 8 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 4 | 51 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 2 - AM | 2 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 6 | 69 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 2 - PM | 20 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 4 | 5 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 2 - PM | 3 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 7 | 76 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 3 - AM | 29 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 5 | 63 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 3 - AM | 3 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Censored by Day 6 | 5 participants |
| Placebo | The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment | Resolved by Day 3 - PM | 42 participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the time to resolution of symptoms where resolution is defined as AOM-SOS score \<=1 on two consecutive occasions.p-value: 0.04Regression, Cox
Primary
The Weighted Average Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, According to Treatment Assignment
The AOM-SOS score is derived from parent scoring each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) associated with AOM as 0, 1 or 2 (none, a little, a lot). The AOM-SOS was administered twice daily the first 3 days of follow-up, then daily for 4 additional days. Symptom burden for each child is determined by calculating the weighted average of symptom scores post-enrollment over the first 7 days of therapy. Scores are weighted by 1/k, where k is the number of post-enrollment assessments taken on that day.
Time frame: During the first 7 days of therapy
Population: The analysis was ITT. The number of participants equals the number of children with at least one AOM-SOS score post-enrollment in the first 7 days of therapy. The score was based on diaries completed at home by the child's parent.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Weighted Average Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, According to Treatment Assignment | 2.79 AOM-SOS score | Standard Error 0.16 |
| Placebo | The Weighted Average Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, According to Treatment Assignment | 3.42 AOM-SOS score | Standard Error 0.18 |
Comparison: Null hypothesis: There is no difference between the two treatment groups regarding the mean weighted average acute otitis media - severity of symptom (AOM-SOS) score (symptom burden), post-enrollment, over the first 7 days of therapy.p-value: 0.01Regression, Linear
Secondary
The Distribution of Children Developing Worsening Symptoms Prior to Receiving 72 Hours of Study Medication According to Treatment Assignment
The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1 and twice daily Days 2 and 3. Each set of ratings was summed to obtain an Acute Otitis Media-Severity of Symptoms (AOM-SOS) score. We compared a child's AOM-SOS scores in the first 72 hours to his/her score at enrollment to determine if a child's symptoms got worse (score increased) or remained unchanged or improved (score remained same or decreased).
Time frame: Before receiving 72 hours of study medication
Population: The analysis was ITT. The number of participants equals the number of children with follow-up whose parent(s) recorded AM and/or PM symptom scores in the first 3 days of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Distribution of Children Developing Worsening Symptoms Prior to Receiving 72 Hours of Study Medication According to Treatment Assignment | Number of children with worsening symptoms | 31 Participants |
| Amoxicillin-Clavulanate | The Distribution of Children Developing Worsening Symptoms Prior to Receiving 72 Hours of Study Medication According to Treatment Assignment | Number of children unchanged or improved | 112 Participants |
| Placebo | The Distribution of Children Developing Worsening Symptoms Prior to Receiving 72 Hours of Study Medication According to Treatment Assignment | Number of children with worsening symptoms | 39 Participants |
| Placebo | The Distribution of Children Developing Worsening Symptoms Prior to Receiving 72 Hours of Study Medication According to Treatment Assignment | Number of children unchanged or improved | 104 Participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of children who develop worsening symptoms within the first 3 days of treatment.p-value: 0.24Regression, Logistic
Secondary
The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment
AOM pathogens are defined as Streptococcus Pneumoniae or Haemophilus Influenzae or Moraxella Catarrhalis or Streptococcus Pyogenes. Nasopharyngeal cultures were obtained at the end of therapy visit.
Time frame: End-of-therapy visit. The mean day for this visit was 11.6.
Population: The analysis was ITT. The number of participants equals the number of children with NP culture results at the end-of-therapy visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of at least one AOM pathogen | 63 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of any AOM pathogen | 67 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of Streptococcus pneumoniae | 18 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of Streptococcus pneumoniae | 112 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of Haemophilus influenzae | 45 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of Haemophilus influenzae | 85 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of Moraxella catarrhalis | 9 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of Moraxella catarrhalis | 121 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of Streptococcus pyogenes | 0 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of Streptococcus pyogenes | 130 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of Moraxella catarrhalis | 93 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of at least one AOM pathogen | 88 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of Haemophilus influenzae | 87 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of any AOM pathogen | 43 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of Streptococcus pyogenes | 128 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of Streptococcus pneumoniae | 46 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of Moraxella catarrhalis | 38 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Absence of Streptococcus pneumoniae | 85 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of Streptococcus pyogenes | 3 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment | Presence of Haemophilus influenzae | 44 participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with at least one AOM pathogen present.p-value: 0.002Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with Streptococcus pneumoniae present.p-value: <0.001Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with Haemophilus influenzae present.p-value: 0.85Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with Moraxella catarrhalis present.p-value: <0.001Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with Streptococcus pyogenes present.p-value: 0.28Regression, Logistic
Secondary
The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment
AOM pathogens are defined as Streptococcus Pneumoniae or Haemophilus Influenzae or Moraxella Catarrhalis or Streptococcus Pyogenes. Nasopharyngeal cultures were obtained at the follow-up visit.
Time frame: Follow-up visit. The mean day for this visit was 22.8.
Population: The analysis was ITT. The number of participants equals the number of children with NP culture results at the follow-up visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of at least one AOM pathogen | 76 participant |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of any AOM pathogen | 52 participant |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of Streptococcus pneumoniae | 26 participant |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of Streptococcus pneumoniae | 102 participant |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of Haemophilus influenzae | 38 participant |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of Haemophilus influenzae | 90 participant |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of Moraxella catarrhalis | 29 participant |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of Moraxella catarrhalis | 99 participant |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of Streptococcus pyogenes | 1 participant |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of Streptococcus pyogenes | 127 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of Moraxella catarrhalis | 99 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of at least one AOM pathogen | 89 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of Haemophilus influenzae | 92 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of any AOM pathogen | 41 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of Streptococcus pyogenes | 130 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of Streptococcus pneumoniae | 42 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of Moraxella catarrhalis | 31 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Absence of Streptococcus pneumoniae | 88 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of Streptococcus pyogenes | 0 participant |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment | Presence of Haemophilus influenzae | 38 participant |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with at least one AOM pathogen present.p-value: 0.1Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with Streptococcus pneumoniae present.p-value: 0.03Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with Haemophilus influenzae present.p-value: 0.96Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with Moraxella catarrhalis present.p-value: 0.79Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of culture results with Streptococcus pyogenes present.p-value: 0.98Regression, Logistic
Secondary
The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the End-of-therapy Visit According to Treatment Assignment
Time frame: End-of-therapy visit. The mean day for this visit was 11.6.
Population: The analysis was ITT. The number of participants equals the number of children with NP culture results and results regarding penicillin susceptibility at the end-of-therapy visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the End-of-therapy Visit According to Treatment Assignment | Colonization with penicillin-susceptible S. pn | 1 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the End-of-therapy Visit According to Treatment Assignment | No colonization with penicillin-susceptible S. pn | 129 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the End-of-therapy Visit According to Treatment Assignment | Colonization with penicillin-susceptible S. pn | 28 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the End-of-therapy Visit According to Treatment Assignment | No colonization with penicillin-susceptible S. pn | 102 participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of children colonized with penicillin-susceptible Streptococcus pneumoniae.p-value: <0.001Regression, Logistic
Secondary
The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the Follow-up Visit
Time frame: Follow-up visit. The mean day for this visit was 22.8.
Population: The analysis was ITT. The number of participants equals the number of children with NP culture results and results regarding penicillin susceptibility at the follow-up visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the Follow-up Visit | No colonization with penicillin-susceptible S. pn | 121 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the Follow-up Visit | Colonization with penicillin-susceptible S. pn | 7 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the Follow-up Visit | Colonization with penicillin-susceptible S. pn | 17 participants |
| Placebo | The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the Follow-up Visit | No colonization with penicillin-susceptible S. pn | 112 participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of children colonized with penicillin-susceptible Streptococcus pneumoniae.p-value: 0.04Regression, Logistic
Secondary
The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment
Analysis was limited to those adverse events identified as being associated with either the study medication or the antimicrobials administered to children who were treatment failures or as being a complication of acute otitis media.
Time frame: We monitored children and queried parents regarding adverse events at each study visit, i.e. Day 4-5, Day 10-12, and Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this visit was 22.8.
Population: The analysis was ITT. The number of participants equals the number of children randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Protocol-defined diarrhea | 36 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Oral thrush | 7 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Perforation of tympanic membrane | 1 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Vomiting | 12 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Diaper dermatitis | 73 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Rash | 1 participants |
| Amoxicillin-Clavulanate | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Mastoiditis | 0 participants |
| Placebo | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Rash | 2 participants |
| Placebo | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Mastoiditis | 1 participants |
| Placebo | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Perforation of tympanic membrane | 7 participants |
| Placebo | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Protocol-defined diarrhea | 22 participants |
| Placebo | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Diaper dermatitis | 51 participants |
| Placebo | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Oral thrush | 1 participants |
| Placebo | The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment | Vomiting | 12 participants |
Comparison: Null hypothesis: There is no difference between the two treatment groups regarding the proportion of children with protocol-defined diarrhea.p-value: 0.04Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two treatment groups regarding the proportion of children with diaper dermatitis.p-value: <0.01Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two treatment groups regarding the proportion of children with oral thrush.p-value: 0.07Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two treatment groups regarding the proportion of children with vomiting.p-value: >0.99Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two treatment groups regarding the proportion of children with rash.p-value: >0.99Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two treatment groups regarding the proportion of children with mastoiditis.p-value: 0.99Regression, Logistic
Comparison: Null hypothesis: There is no difference between the two treatment groups regarding the proportion of children with perforation of their tympanic membrane.p-value: 0.08Regression, Logistic
Secondary
The Distribution of Clinical Failures by the End-of-therapy Visit According to Treatment Assignment
Clinical failure by the end of therapy visit is defined as failure to achieve complete or virtually complete resolution of symptoms and of otoscopic signs, but without regard to the persistence of middle ear effusion.
Time frame: End-of-therapy visit. The mean day for this visit was 11.6.
Population: The analysis was ITT. The number of participants equals the number of children evaluated post therapy plus the number of children who met the criteria for clinical failure prior to the end of therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Distribution of Clinical Failures by the End-of-therapy Visit According to Treatment Assignment | Clinical failures by the end of therapy visit | 23 participants |
| Amoxicillin-Clavulanate | The Distribution of Clinical Failures by the End-of-therapy Visit According to Treatment Assignment | Subjects not classified as clinical failures | 119 participants |
| Placebo | The Distribution of Clinical Failures by the End-of-therapy Visit According to Treatment Assignment | Clinical failures by the end of therapy visit | 73 participants |
| Placebo | The Distribution of Clinical Failures by the End-of-therapy Visit According to Treatment Assignment | Subjects not classified as clinical failures | 70 participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of clinical failures by the end of therapy.p-value: <0.001Regression, Logistic
Secondary
The Distribution of Clinical Failures by the On-therapy Visit According to Treatment Assignment
Clinical failure by the on-therapy visit is defined as either failure to achieve substantial improvement in symptoms, or worsening of otoscopic signs, or both.
Time frame: On-therapy visit. The mean day for this visit was 5.0.
Population: The analysis was ITT. The number of participants equals the number of children followed at least 72 hours after the initial dose of study medication plus the number of children meeting the criteria for clinical failure less than 72 hours after the initial dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Distribution of Clinical Failures by the On-therapy Visit According to Treatment Assignment | Clinical failures by the on therapy visit | 5 participants |
| Amoxicillin-Clavulanate | The Distribution of Clinical Failures by the On-therapy Visit According to Treatment Assignment | Subjects not classified as clinical failures | 138 participants |
| Placebo | The Distribution of Clinical Failures by the On-therapy Visit According to Treatment Assignment | Clinical failures by the on therapy visit | 34 participants |
| Placebo | The Distribution of Clinical Failures by the On-therapy Visit According to Treatment Assignment | Subjects not classified as clinical failures | 111 participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of clinical treatment failures by the on-therapy visit.p-value: <0.001Regression, Logistic
Secondary
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment
The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 and 3, then once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score as a measure of symptom burden. The maximum possible score was 14 and the minimum was 0.
Time frame: During the first 7 days of therapy
Population: The analysis was ITT. The number of participants equals the number of children with at least one AOM-SOS score post-enrollment in the first 7 days of therapy. The score was based on AM and PM diaries completed at home by the child's parent.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-Clavulanate | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 2 AM | 4.12 AOM-SOS score | Standard Deviation 3.06 |
| Amoxicillin-Clavulanate | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 4 | 2.40 AOM-SOS score | Standard Deviation 2.62 |
| Amoxicillin-Clavulanate | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 3 AM | 2.86 AOM-SOS score | Standard Deviation 2.69 |
| Amoxicillin-Clavulanate | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 5 | 1.93 AOM-SOS score | Standard Deviation 2.09 |
| Amoxicillin-Clavulanate | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 2 PM | 3.78 AOM-SOS score | Standard Deviation 3.05 |
| Amoxicillin-Clavulanate | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 6 | 1.40 AOM-SOS score | Standard Deviation 1.69 |
| Amoxicillin-Clavulanate | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 3 PM | 2.82 AOM-SOS score | Standard Deviation 2.67 |
| Amoxicillin-Clavulanate | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 7 | 1.28 AOM-SOS score | Standard Deviation 1.64 |
| Amoxicillin-Clavulanate | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 1 PM | 5.80 AOM-SOS score | Standard Deviation 3.61 |
| Placebo | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 7 | 1.94 AOM-SOS score | Standard Deviation 2.5 |
| Placebo | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 1 PM | 6.20 AOM-SOS score | Standard Deviation 3.33 |
| Placebo | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 2 AM | 4.85 AOM-SOS score | Standard Deviation 3.54 |
| Placebo | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 2 PM | 4.33 AOM-SOS score | Standard Deviation 3.41 |
| Placebo | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 3 AM | 3.37 AOM-SOS score | Standard Deviation 3.04 |
| Placebo | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 3 PM | 3.25 AOM-SOS score | Standard Deviation 2.94 |
| Placebo | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 4 | 2.68 AOM-SOS score | Standard Deviation 2.59 |
| Placebo | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 5 | 2.41 AOM-SOS score | Standard Deviation 2.59 |
| Placebo | The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment | Day 6 | 2.31 AOM-SOS score | Standard Deviation 2.29 |
Comparison: Null hypothesis: There is no difference between the two groups regarding the symptom burden as measured by the respective mean scores over time.p-value: 0.02Generalized estimating equations
Secondary
The Mean Number of Antibiotic Prescriptions, Exclusive of Study Medication, According to Treatment Assignment
This is the number of times, in the course of the study, a child required treatment with an antibiotic other than the blinded study medication.
Time frame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
Population: The analysis was ITT. The participants for analysis were the children with follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Mean Number of Antibiotic Prescriptions, Exclusive of Study Medication, According to Treatment Assignment | .35 antibiotic prescriptions | Standard Deviation 0.58 |
| Placebo | The Mean Number of Antibiotic Prescriptions, Exclusive of Study Medication, According to Treatment Assignment | .75 antibiotic prescriptions | Standard Deviation 0.73 |
Comparison: Null hypothesis: There is no difference between the two groups regarding the number of antibiotic prescriptions, exclusive of the blinded study medication.p-value: <0.001Generalized estimating equations
Secondary
The Mean Number of Emergency Room Visits According to Treatment Assignment
At each visit we asked parents if they had to take their child to the emergency department. We also reviewed medical records to assure even more accurate reporting.
Time frame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
Population: The analysis was ITT. The participants for analysis were the children with follow-up assessment visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Mean Number of Emergency Room Visits According to Treatment Assignment | .07 visits to ER | Standard Deviation 0.26 |
| Placebo | The Mean Number of Emergency Room Visits According to Treatment Assignment | .07 visits to ER | Standard Deviation 0.25 |
Comparison: Null hypothesis: There is no difference between the two groups regarding visits to emergency roomp-value: 0.9Generalized estimating equations
Secondary
The Mean Number of Times Analgesic Medication Was Administered to the Child According to Treatment Assignment
The parents were asked to complete a memory aid for the first 10 days of the study. One item asked them to record medications administered to the child in addition to the study medication. The data presented shows the mean number of times analgesic, i.e. ibuprofen or acetaminophen, was administered.
Time frame: The first 10 days of follow-up
Population: The analysis was ITT. The participants for analysis were the children with follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Mean Number of Times Analgesic Medication Was Administered to the Child According to Treatment Assignment | .37 times analgesic was administered | Standard Deviation 0.48 |
| Placebo | The Mean Number of Times Analgesic Medication Was Administered to the Child According to Treatment Assignment | .43 times analgesic was administered | Standard Deviation 0.48 |
Comparison: Null hypothesis: There is no difference between the two groups regarding the average number of doses of analgesic medication administered by parents.p-value: 0.35Regression, Linear
Secondary
The Mean Number of Visits to a Primary Care Provider (PCP) According to Treatment Assignment
At each visit parents were asked if they had taken their child to his/her primary care physician since the last contact. Medical records were also reviewed.
Time frame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
Population: The analysis was ITT. The participants for analysis were the children with follow-up assessment visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Mean Number of Visits to a Primary Care Provider (PCP) According to Treatment Assignment | .15 visits to PCP | Standard Deviation 0.4 |
| Placebo | The Mean Number of Visits to a Primary Care Provider (PCP) According to Treatment Assignment | .23 visits to PCP | Standard Deviation 0.5 |
Comparison: Null hypothesis: There is no difference between the two groups regarding visits to primary care provider.p-value: 0.2Generalized estimating equations
Secondary
The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the End-of-therapy Visit According to Treatment Assignment
Parents were asked to circle the expression that best represented their satisfaction with the study medication. These expressions have an assigned value: Very dissatisfied = 1, Somewhat dissatisfied = 2, Neither satisfied nor dissatisfied = 3, Somewhat satisfied = 4 and Very satisfied = 5.
Time frame: End-of-therapy visit. The mean day for this visit was 11.6.
Population: The analysis was ITT. The number of participants equals the number of children whose parent reported a satisfaction score at the end-of-therapy visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the End-of-therapy Visit According to Treatment Assignment | 4.40 parental satisfaction score | Standard Deviation 0.92 |
| Placebo | The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the End-of-therapy Visit According to Treatment Assignment | 4.12 parental satisfaction score | Standard Deviation 1.16 |
Comparison: Null hypothesis: There is no difference between the groups regarding the mean parental satisfaction score at the end-of-therapy visit.p-value: 0.04Regression, Linear
Secondary
The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment
Parents were asked to circle the expression that best represented their satisfaction with the study medication. These expressions have an assigned value: Very dissatisfied = 1, Somewhat dissatisfied = 2, Neither satisfied nor dissatisfied = 3, Somewhat satisfied = 4 and Very satisfied = 5.
Time frame: Follow-up visit. The mean day for this visit was 22.8.
Population: The analysis was ITT. The number of participants equals the number of children whose parent reported a satisfaction score at the follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment | 4.53 parental satisfaction score | Standard Deviation 0.89 |
| Placebo | The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment | 4.17 parental satisfaction score | Standard Deviation 1.12 |
Comparison: Null hypothesis: There is no difference between the groups regarding the mean parental satisfaction score at the follow-visit visit.p-value: 0.005Regression, Linear
Secondary
The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the On-therapy Visit According to Treatment Assignment
Parents were asked to circle the expression that best represented their satisfaction with the study medication. These expressions have an assigned value: Very dissatisfied = 1, Somewhat dissatisfied = 2, Neither satisfied nor dissatisfied = 3, Somewhat satisfied = 4 and Very satisfied = 5.
Time frame: On-therapy visit. The mean day for this visit was 5.0.
Population: The analysis was ITT. The number of participants equals the number of children whose parent reported a satisfaction score at the on-therapy visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-Clavulanate | The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the On-therapy Visit According to Treatment Assignment | 4.19 parental satisfaction score | Standard Deviation 0.97 |
| Placebo | The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the On-therapy Visit According to Treatment Assignment | 4.13 parental satisfaction score | Standard Deviation 1.06 |
Comparison: Null hypothesis: There is no difference between the groups regarding the mean parental satisfaction score at the on-therapy visit.p-value: 0.71Regression, Linear
Secondary
The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the End-of-therapy Visit According to Treatment Assignment
For tympanograms with values for height, middle-ear air pressure, and gradient width, the probability of Middle Ear Effusion (MEE) was estimated by applying an algorithm developed by Smith et al. If the tympanogram was flat and had no printed values for the 3 fields, the probability of MEE was estimated to be .802 based on the proportion of ears with flat graphs that were found otoscopically, by Smith et al, to have MEE.
Time frame: End-of-therapy visit. The mean day for this visit was 11.6.
Population: The analysis was ITT. The number of participants equals the number of children for which at least one ear has an interpretable tympanogram at the end-of-therapy visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-Clavulanate | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the End-of-therapy Visit According to Treatment Assignment | Right ear | .32 probability of effusion | Standard Deviation 0.27 |
| Amoxicillin-Clavulanate | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the End-of-therapy Visit According to Treatment Assignment | Left ear | .33 probability of effusion | Standard Deviation 0.28 |
| Placebo | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the End-of-therapy Visit According to Treatment Assignment | Right ear | .41 probability of effusion | Standard Deviation 0.28 |
| Placebo | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the End-of-therapy Visit According to Treatment Assignment | Left ear | .41 probability of effusion | Standard Deviation 0.27 |
Comparison: Null hypothesis: There is no difference between the two groups regarding the probability of middle ear effusion at the end-of-therapy visit.p-value: 0.006Generalized estimating equations
Secondary
The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the Follow-up Visit According to Treatment Assignment
For tympanograms with values for height, middle-ear air pressure, and gradient width, the probability of Middle Ear Effusion (MEE) was estimated by applying an algorithm developed by Smith et al. If the tympanogram was flat and had no printed values for the 3 fields, the probability of MEE was estimated to be .802 based on the proportion of ears with flat graphs that were found otoscopically, by Smith et al, to have MEE.
Time frame: Follow-up visit. The mean day for this visit was 22.8.
Population: The analysis was ITT. The number of participants equals the number of children for which at least one ear has an interpretable tympanogram at the follow-up visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-Clavulanate | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the Follow-up Visit According to Treatment Assignment | Right ear | .28 probability of effusion | Standard Deviation 0.28 |
| Amoxicillin-Clavulanate | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the Follow-up Visit According to Treatment Assignment | Left ear | .27 probability of effusion | Standard Deviation 0.3 |
| Placebo | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the Follow-up Visit According to Treatment Assignment | Right ear | .32 probability of effusion | Standard Deviation 0.29 |
| Placebo | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the Follow-up Visit According to Treatment Assignment | Left ear | .37 probability of effusion | Standard Deviation 0.31 |
Comparison: The analysis was ITT. The number of participants equals the number of children for which at least one ear has an interpretable tympanogram at the follow-up visit.p-value: 0.04Generalized estimating equations
Secondary
The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the On-therapy Visit According to Treatment Assignment
For tympanograms with values for height, middle-ear air pressure, and gradient width, the probability of Middle Ear Effusion (MEE) was estimated by applying an algorithm developed by Smith et al. If the tympanogram was flat and had no printed values for the 3 fields, the probability of MEE was estimated to be .802 based on the proportion of ears with flat graphs that were found otoscopically, by Smith et al, to have MEE.
Time frame: On-therapy visit. The mean day for this visit was 5.0.
Population: The analysis was ITT. The number of participants equals the number of children for which at least one ear has an interpretable tympanogram at the on-therapy visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-Clavulanate | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the On-therapy Visit According to Treatment Assignment | Right ear | .36 probability of effusion | Standard Deviation 0.29 |
| Amoxicillin-Clavulanate | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the On-therapy Visit According to Treatment Assignment | Left ear | .39 probability of effusion | Standard Deviation 0.31 |
| Placebo | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the On-therapy Visit According to Treatment Assignment | Right ear | .42 probability of effusion | Standard Deviation 0.29 |
| Placebo | The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the On-therapy Visit According to Treatment Assignment | Left ear | .48 probability of effusion | Standard Deviation 0.29 |
Comparison: Null hypothesis: There is no difference between the two groups regarding the probability of middle ear effusion at the on-therapy visit.p-value: 0.03Generalized estimating equations
Secondary
The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Having Missed Work According to Treatment Assignment
At each visit, parent or parents were asked if their child's illness had caused either parent to miss a day or partial day of work. The total number of visits is summed across all participants in the respective treatment arms.
Time frame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
Population: The analysis was ITT. The participants for analysis were the children with follow-up assessment visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amoxicillin-Clavulanate | The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Having Missed Work According to Treatment Assignment | 33 visits |
| Placebo | The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Having Missed Work According to Treatment Assignment | 33 visits |
Comparison: Null hypothesis: There is no difference between the two groups regarding the visits at which family member reported missing work, i.e. number of such visits / total number of follow-up assessment visits.p-value: 0.93Generalized estimating equations
Secondary
The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Making Special Daycare Arrangements According to Treatment Assignment
At each visit, parent or parents were asked if their child's illness had caused them to make alternative daycare arrangements. The total number of visits is summed across all participants in the respective treatment arms.
Time frame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
Population: The analysis was ITT. The participants for analysis were the children with follow-up assessment visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amoxicillin-Clavulanate | The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Making Special Daycare Arrangements According to Treatment Assignment | 22 visits |
| Placebo | The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Making Special Daycare Arrangements According to Treatment Assignment | 24 visits |
Comparison: Null hypothesis: There is no difference between the two groups regarding the visits at which family member reported making special daycare arrangements, i.e. number of such visits / total number of follow-up assessment visits.p-value: 0.66Generalized estimating equations