Acute Otitis Media
Conditions
Keywords
ear infection, antibiotics, infants, children, pediatrics, tympanostomy tubes
Brief summary
To determine whether tympanostomy tube placement (TTP) compared with nonsurgical management will meaningfully improve children's acute otitis media (AOM) experience over the succeeding 2 years.
Detailed description
Tympanostomy tube placement (TTP) for recurrent acute otitis media (rAOM) is frequently performed in children under 3 years of age; however, a critical need exists to establish its risk/benefit ratio. Seventy percent of children experience at least one episode of AOM during the first year of life; 20% of children have rAOM. The efficacy of TTP for preventing rAOM, assumedly by maintaining middle-ear ventilation, remains unclear. Benefits of TTP must be balanced against risks of anesthesia, complications and sequelae of surgery, and cost. Accordingly, the objective of this proposal is to determine the efficacy of TTP in children aged 6-35 months, the group in which rAOM is most troublesome. The central hypothesis is that in children with rAOM, the operation will prove effective over the ensuing 2 years overall, but the benefit in a more severely affected, and therefore higher-risk subgroup may be substantially greater than in a less severely affected subgroup, in whom benefits may not outweigh risks. The rationale for this research is based on a belief that the limited nature of the benefit of TTP found in earlier clinical trials may have been the result of enrolling children whose illnesses had not been diagnosed using stringent criteria and/or whose ascertainment of episodes had relied on undocumented histories. The primary objective is to determine the extent to which TTP reduces the overall rate of recurrences in children with rAOM over a 2-year period. In a randomized, clinical trial, children aged 6-35 months who are at risk for rAOM will be followed prospectively and examined promptly with new respiratory illnesses to accurately document episodes of AOM. A total of 240 children who meet stringent inclusion criteria for rAOM will be eligible to undergo randomization within strata (age and exposure to other children) to receive TTP or nonsurgical management. Children will be followed for 2 years; the average number of episodes of AOM will be documented and compared between groups. The secondary objective is to determine changes following TTP in nasopharyngeal (NP) colonization with resistant bacteria. At the time of randomization and 3 times a year for 2 years, NP specimens will be obtained and cultured. Susceptibility testing and serotyping will be performed, and the proportions of children colonized with resistant bacteria compared between treatment groups. The tertiary objective is to determine cost-effectiveness of TTP. The investigators will calculate both direct medical and nonmedical costs and correlate this with the number of days that each child has AOM symptoms, otorrhea, and any adverse events or complications. The proposed research is innovative, as the investigators will document AOM episodes prospectively using stringent diagnostic criteria and obtain digital tympanic membrane images otoendoscopically to enhance accuracy of observations. Findings of the proposed study will provide clinicians and parents with dependable evidence concerning the overall effects of TTP compared with nonsurgical management in children with rAOM of varying degrees of severity, enabling evidence-based decisions regarding an important component of the children's healthcare.
Interventions
As per routine care, tympanostomy tubes will be inserted under general anesthesia, using a small radial incision in the anteroinferior portion of the tympanic membrane; a Teflon® Armstrong-type tympanostomy tube will be used.
DRUGAmoxicillin-Clavulanate and/or Ceftriaxone
Children randomized to nonsurgical management will receive stepwise therapy with amoxicillin-clavulanate (90/6.4 mg/kg in two divided doses for 10 days), and in the event of inadequate response, ceftriaxone (75 mg/kg intramuscularly, repeated in 48 hours), as recommended in the American Academy of Pediatrics guidelines.
DRUGOfloxacin Otic
Participants randomized to receive tympanostomy tubes will also be followed overtime for recurrences of AOM and treated with topical ofloxacin (Floxin® 0.3%, 5 mL) 5 drops into the affected ear twice daily for 10 days. Persistence of otorrhea after 7 days of treatment will be considered inadequate response, and children so affected will be prescribed empiric amoxicillin-clavulanate (90/6.4 mg/kg/day in two divided doses) followed by culture-directed therapy 48 hours later.
Sponsors
George Washington University
National Institute on Deafness and Other Communication Disorders (NIDCD)
Alejandro Hoberman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Subjects in the randomization phase of the study will be randomized to either medical management or tube surgery. No masking will occur.
Eligibility
Sex/Gender
ALL
Age
6 Months to 35 Months
Healthy volunteers
No
Inclusion criteria
1. are aged 6-35 months, 2. have rAOM, defined as the occurrence of 3 AOM episodes in 6 months or 4 episodes in 12 months with ≥1 episode in the preceding 6 months, and 3. 2 of these AOM episodes have been documented by trained study personnel.
Exclusion criteria
1. have a history of TTP, 2. have a chronic illness (cystic fibrosis, neoplasm, juvenile diabetes, renal or hepatic insufficiency, immune dysfunction, malabsorption, inflammatory bowel disease, severe asthma requiring at least 4 courses of oral corticosteroids during the last 12 months), 3. are allergic to amoxicillin, 4. have a congenital anomaly that might increase the risk of recurrences (e.g., cleft palate, Down's syndrome), 5. have had otitis media effusion for at least 3 months in addition to rAOM, or 6. have sensorineural hearing loss.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year | Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years. For each child with incomplete 2-year follow-up, multiple imputation was used and values for the remaining days/years were imputed. | An episode of AOM is considered a discrete occurrence if symptoms and signs persisted for, or recurred, 17 or more days after the start of antimicrobial treatment. The rate is calculated by dividing the total number of occurrences by the total number of years of follow-up. Multiple imputation was used when follow-up was incomplete. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Frequency Distribution of AOM Episodes Among Children Completing the Study | Day 1 until Day 786. For children completing the study, the mean length of follow-up was 726 days. | An episode of AOM is considered a discrete occurrence if symptoms and signs persisted for, or recurred, 17 or more days after the start of antimicrobial treatment. Children with at least 23 months of follow-up were considered to have completed the study. |
| The Distribution of Children Experiencing Treatment Failure (TF) | Day 1 until Day 786. | Parents used the Acute Otitis Media Severity of Symptoms (AOM-SOS) scale (version 4.0) to rate each of 5 symptoms as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Total scores range from 0 to 10; higher scores indicate greater severity of symptoms. AOM episodes were categorized as likely severe if the parent described the child as having moderate or severe otalgia (a lot of ear tugging), temperature ≥39°C, or an AOM-SOS scale score \>6 Day 1 of the episode. TF is defined as frequent AOM recurrences (2 in 3 months, 3 in 6 or 4 in 12); ≥3 likely severe AOM recurrences, receipt of ≥45 cumulative days of systemic antimicrobial treatment for AOM, otorrhea for ≥45 cumulative days or diarrhea associated with antimicrobial treatment for ≥30 cumulative days, respectively, in 12 months; persistent effusion for ≥12 successive months; TM perforation for ≥90 days; AOM related hospitalization; anesthesia reactions; and tubes in children randomized to nonsurgical management. |
| The Time to the First Episode of AOM | Day 1 until Day 786. The mean length of follow-up was 662 days / 21.8 months. | The time to the first episode of AOM is defined as the time, expressed in months, from randomization until the first episode of AOM. |
| The Distribution of AOM Episodes Categorized as Probably Severe or Probably Nonsevere | Day 1 until Day 786. | The American Academy of Pediatrics clinical practice guideline concerning the management of AOM refers to children with severe signs or symptoms as those with moderate or severe otalgia or otalgia for \>= 48 hours or temperature 39°C (102.2°F) or higher. To simulate that definition, scores are used from the 5-item Acute Otitis Media Severity of Symptoms (AOM-SOS) scale (version 4.0) in which parents are asked to rate symptoms, as compared with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Total scores range from 0 to 10, with higher scores indicating greater severity of symptoms. AOM episodes are categorized as probably severe if the parent described the child as having had moderate or severe otalgia (a lot of ear tugging; i.e. a score of 2), temperature \>=39°C, or an AOM-SOS scale score \>6 on Day 1 of the episode. If not probably severe, then the episode is categorized as probably nonsevere. |
| The Distribution of AOM Episodes Presenting With Tympanic Membrane Bulging or Otorrhea | Day 1 until Day 786. | The presence of either tympanic membrane bulging or tympanic membrane perforation with purulent otorrhea, in addition to documentation of symptoms, is required for each episode of AOM. |
| The Mean Days Per Year Children Experience Tube Otorrhea | Day 1 until Day 786. The mean length of follow-up was 662 days / 1.8 years. | Adverse events, including tube-associated otorrhea, were collected from enrollment through the end of study. Each study visit included a review of adverse events. Any such event that occurred since the previous visit was recorded, including the date of onset and the date of resolution. For each child, the days per year of tube otorrhea is calculated by dividing the total number of days of tube otorrhea (based on dates of onset and resolution) by the total number of years of follow-up. |
| The Mean Days Per Year Children Experience AOM Symptoms With an Intact Tympanic Membrane (TM) | Day 1 until Day 786. The mean length of follow-up was 662 days / 1.8 years. | For a given child, if a day of follow-up coincides with a study visit, the status of the right and left TMs are recorded at the ear exam. If a day of follow-up does not coincide with a study visit the status of each TM is assumed to be the same as the status on the prior day. Scores are used from the 5-item Acute Otitis Media Severity of Symptoms (AOM-SOS) scale (version 4.0) in which parents are asked to rate symptoms, as compared with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Total scores range from 0 to 10, with higher scores indicating greater severity of symptoms. Scores are recorded at study visits and on diaries. The total number of days with an intact TM and a AOM-SOS score greater than or equal to 1 is divided by the total number of years of follow-up to arrive at the days per year with AOM symptoms and an intact TM. |
| The Mean Days Per Year Children Receive Systemic Antimicrobials for AOM | Day 1 until Day 786. The mean length of follow-up was 662 days / 1.8 years. | Systemic antibiotics include Amoxicillin-Clavulanate, Ceftriaxone, Cefdinir, Amoxicillin, Azithromycin, Clindamycin, Levofloxacin, Bactrim, Cefprozil, Omnicef and Trimethoprim-Sulfamethoxazole. The days per year, for each child, is calculated by dividing the total number of days the child receives systemic antimicrobials for AOM (based on the recorded start and stop dates) by the total number of years of follow-up. |
| The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported | Day 1 until Day 786. | PDD is defined as the occurrence of three or more watery stools on 1 day or two or more watery stools on each of 2 consecutive days. Adverse events, including PDD, were collected from enrollment through the end of study. Each study visit included a review of medication-related adverse events. Any such event that occurred since the previous visit was recorded. |
| The Distribution of Children for Whom Diaper Dermatitis Was Reported | Day 1 until Day 786. | Diaper dermatitis is defined as diaper rash necessitating administration of topical antifungal therapy. Adverse events, including diaper dermatitis, were collected from enrollment through the end of study. Each study visit included a review of medication-related adverse events. Any such event that occurred since the previous visit was recorded. |
| The Distribution of Children for Whom Tube Otorrhea Was Reported | Day 1 until Day 786. | Adverse events, including tube-associated otorrhea, were collected from enrollment through the end of study. Each study visit included a review of adverse events. Any such event that occurred since the previous visit was recorded. |
| The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year According to the Estimated Risk of Acute Otitis Media (AOM) Recurrences at Enrollment | Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years. For each child with incomplete 2-year follow-up, multiple imputation was used and values for the remaining days/years were imputed. | An episode of AOM is considered a discrete occurrence if symptoms and signs persisted for, or recurred, \>=17 days after the start of antimicrobial treatment. The rate is calculated by dividing the total # of occurrences by the total # of years of follow-up. Risk of recurrences was based on early age of onset of AOM; numerous and/or frequent previous AOM episodes; receipt of multiple courses of antibiotic; eligibility for enrollment first evident during warm-weather months; parental characterization of previous AOM episodes as severe; eligibility for enrollment despite nonexposure to other young children; moderate or marked tympanic membrane (TM) bulging with previous AOM episodes; most previous AOM episodes in both ears; and a high score on the Acute Otitis Media Severity of Symptom scale (with scores ranging from 0 to 10 and higher scores indicating greater severity of symptoms) during screening and/or at enrollment. Multiple imputation was used when follow-up was incomplete. |
| The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Episodes of AOM | Day 1 until Day 786. | Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (S. pn) and ß-lactamase-positive Haemophilus influenzae (H. flu). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of \>1 μg/mL. |
| The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Routine Non-Illness Visits | Day 1 until Day 786. | Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (S. pm) and ß-lactamase-positive Haemophilus influenzae (H. flu). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of \>1 μg/mL. |
| The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at AOM Episodes Late During the Respiratory Season (April-May) | April 1 to May 31, each of the 2 years of follow-up. The mean length of follow-up was 111 days / 3.7 months. | Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (S. pn) and ß-lactamase-positive Haemophilus influenzae (H. flu). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of \>1 μg/mL. |
| The Mean Score Representing Parental Satisfaction With Clinical Management | The end-of-study visit. The mean day for this visit was 726. | At the end-of-study visit, parents were asked to rate their level of satisfaction with their child's assigned management using a 5-point scale with higher numbers indicating greater satisfaction, specifically 1 = very dissatisfied, 2 = somewhat dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = somewhat satisfied, and 5 = very satisfied. |
| The Distribution of Parent Reports Indicating At Least One Health Care Encounter Since the Previous Study Visit as an Indicator of Medical Resource Use | Day 1 until Day 786. | Health care encounters, indicators of medical resource use, were ascertained from parent reports. At scheduled study visits, every 8 weeks after randomization. and at interim sick study visits, parents were asked about encounters with healthcare providers, including hospitalizations and visits to emergency departments, urgent care, and primary care providers, since the previous study visit. |
| The Distribution of Reported Occurrences of a Parent Missing Work Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Day 1 until Day 786. | Occurrences of parent missing work due to child's illness, an indicator of non-medical resource use, was ascertained from parent reports at scheduled study visits, every 8 weeks after randomization, and at interim sick study visits. |
| The Distribution of Reported Occurrences of the Need for Special Childcare Arrangements Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Day 1 until Day 786. | Occurrences of the need for special childcare arrangements due to child's illness, an indicator of non-medical resource use, was ascertained from parent reports at scheduled study visits, every 8 weeks after randomization, and at interim sick study visits. |
| The Mean Scores on the 6 Item Quality of Life Survey Questionnaire (OM-6) | Day 1 until Day 786. | The OM-6 is a 6 item quality of life assessment addressing physical suffering, hearing loss, speech impairment, emotional distress, activity limitations and caregiver concerns. Responses are regarded on an ordinal scale ranging from 1 (no problem) to 7 (greatest problem). The average response, i.e., score, for these 6 items is calculated. The overall child's quality of life (QOL) score, also captured on the OM-6, is expressed on an ordinal response scale that ranges from 0 (worst quality of life) to 10 (best quality). A OM-6 is administered to the parent every 16 weeks after randomization and occasionally at sick visits. |
| The Mean Scores on the 6 Item Caregiver Impact Questionnaire (CIQ) | Day 1 until Day 786. | The Caregiver Impact Questionnaire (CIQ) is a 6 item assessment addressing lack of sleep, absence from work or education, canceling of family activities, changing daily activities, feeling nervous and feeling helpless. Each of these responses is expanded to a continuous scale from 0 (no impact on caregiver) to 100 (greatest impact). The average response, i.e., score, for these 6 items is calculated. The overall caregiver's quality of life (QOL) score, also captured on the CIQ, is expressed on a ordinal response scale that ranges from 0 (worst quality of life) to 10 (best quality). The CIQ is administered to the parent every 16 weeks after randomization and occasionally at sick visits. |
| The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness | Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years. | Total costs in US dollars were calculated by summing costs of lost wages, office visits, medical procedures, hospitalizations, and medications. Total QALDs were calculated by summing daily utility values. A utility value of 1.0 was assumed for days without AOM, otorrhea, or hospitalization. For days where these states were reported, published utility values associated with each state were used. To arrive at the final measure, total costs were divided by total utility values. |
| The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness According to the Estimated Risk of Acute Otitis Media Recurrences at Enrollment | Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years. | Total costs in US dollars were calculated by summing costs of lost wages, office visits, medical procedures, hospitalizations, and medications. Total QALDs were calculated by summing daily utility values. A utility value of 1.0 was assumed for days without AOM, otorrhea, or hospitalization. For days where these states were reported, published utility values associated with each state were used. To arrive at the final measure, total costs were divided by total utility values. The estimated risk of AOM at enrollment is described under both Baseline Characteristics and Outcome Measure #2. |
| The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | Day 1 until Day 786. | Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae and ß-lactamase-positive Haemophilus influenzae. Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of \>1 μg/mL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Surgical Management Tympanostomy Tube Placement Topical antimicrobial treatment of acute otitis media episodes with ofloxacin drops
Tympanostomy tube placement: As per routine care, tympanostomy tubes will be inserted under general anesthesia, using a small radial incision in the anteroinferior portion of the tympanic membrane; a Teflon® Armstrong-type tympanostomy tube will be used.
Ofloxacin Otic: Participants randomized to receive tympanostomy tubes will also be followed overtime for recurrences of AOM and treated with topical ofloxacin (Floxin® 0.3%, 5 mL) 5 drops into the affected ear twice daily for 10 days. Persistence of otorrhea after 7 days of treatment will be considered inadequate response, and children so affected will be prescribed empiric amoxicillin-clavulanate (90/6.4 mg/kg/day in two divided doses) followed by culture-directed therapy 48 hours later. | 129 |
| Non-Surgical Management Antimicrobial treatment of acute otitis media episodes with amoxicillin-clavulanate and/or ceftriaxone
Amoxicillin-Clavulanate and/or Ceftriaxone: Children randomized to nonsurgical management will receive stepwise therapy with amoxicillin-clavulanate (90/6.4 mg/kg in two divided doses for 10 days), and in the event of inadequate response, ceftriaxone (75 mg/kg intramuscularly, repeated in 48 hours), as recommended in the American Academy of Pediatrics guidelines. | 121 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Follow-up less than 23 months | 16 | 20 |
| Overall Study | No follow-up post-randomization | 5 | 1 |
Baseline characteristics
| Characteristic | Surgical Management | Total | Non-Surgical Management |
|---|---|---|---|
| Age, Customized 12-23 months | 70 Participants | 137 Participants | 67 Participants |
| Age, Customized 24-35 months | 13 Participants | 22 Participants | 9 Participants |
| Age, Customized 6-11 months | 46 Participants | 91 Participants | 45 Participants |
| Estimated Risk of Recurrences of Acute Otitis Media (AOM) High risk | 66 Participants | 115 Participants | 49 Participants |
| Estimated Risk of Recurrences of Acute Otitis Media (AOM) Low risk | 63 Participants | 135 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 29 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 110 Participants | 221 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Exposure to Other Children No | 26 Participants | 48 Participants | 22 Participants |
| Exposure to Other Children Yes | 103 Participants | 202 Participants | 99 Participants |
| Maternal Level of Education College graduate | 52 Participants | 108 Participants | 56 Participants |
| Maternal Level of Education High school graduate or equivalent | 62 Participants | 117 Participants | 55 Participants |
| Maternal Level of Education Less than high school | 6 Participants | 10 Participants | 4 Participants |
| Maternal Level of Education Unknown | 9 Participants | 15 Participants | 6 Participants |
| Otitis Media With Effusion (OME) Present at Randomization No | 85 Participants | 156 Participants | 71 Participants |
| Otitis Media With Effusion (OME) Present at Randomization Yes | 44 Participants | 94 Participants | 50 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 41 Participants | 83 Participants | 42 Participants |
| Race (NIH/OMB) More than one race | 10 Participants | 17 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 70 Participants | 140 Participants | 70 Participants |
| Sex: Female, Male Female | 42 Participants | 90 Participants | 48 Participants |
| Sex: Female, Male Male | 87 Participants | 160 Participants | 73 Participants |
| Site of Enrollment Children's Hospital of Pittsburgh (CHP) | 92 Participants | 183 Participants | 91 Participants |
| Site of Enrollment Children's National Medical Center (CNMC) | 20 Participants | 36 Participants | 16 Participants |
| Site of Enrollment Kentucky Pediatric and Adult Research (KPAR) | 17 Participants | 31 Participants | 14 Participants |
| Type of Health Insurance None | 4 Participants | 4 Participants | 0 Participants |
| Type of Health Insurance Private | 62 Participants | 124 Participants | 62 Participants |
| Type of Health Insurance Public | 63 Participants | 122 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 129 | 0 / 121 |
| other Total, other adverse events | 98 / 129 | 70 / 121 |
| serious Total, serious adverse events | 3 / 129 | 7 / 121 |
Outcome results
Primary
The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year
An episode of AOM is considered a discrete occurrence if symptoms and signs persisted for, or recurred, 17 or more days after the start of antimicrobial treatment. The rate is calculated by dividing the total number of occurrences by the total number of years of follow-up. Multiple imputation was used when follow-up was incomplete.
Time frame: Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years. For each child with incomplete 2-year follow-up, multiple imputation was used and values for the remaining days/years were imputed.
Population: The analysis was intention-to-treat (ITT). The participants are randomized children. For each child with incomplete 2-year follow-up, the total number of episodes of acute otitis media were imputed using multivariate imputation by chained equations with 50 imputations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Surgical Management | The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year | 1.48 Occurrences per child-year | Standard Error 0.08 |
| Non-Surgical Management | The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year | 1.56 Occurrences per child-year | Standard Error 0.08 |
Comparison: Null hypothesis: There is no difference between the two groups in the rate of occurrence of AOM per child-year during the 2-year follow-up period.p-value: 0.6695% CI: [0.84, 1.12]Generalized linear model
Secondary
The Distribution of AOM Episodes Categorized as Probably Severe or Probably Nonsevere
The American Academy of Pediatrics clinical practice guideline concerning the management of AOM refers to children with severe signs or symptoms as those with moderate or severe otalgia or otalgia for \>= 48 hours or temperature 39°C (102.2°F) or higher. To simulate that definition, scores are used from the 5-item Acute Otitis Media Severity of Symptoms (AOM-SOS) scale (version 4.0) in which parents are asked to rate symptoms, as compared with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Total scores range from 0 to 10, with higher scores indicating greater severity of symptoms. AOM episodes are categorized as probably severe if the parent described the child as having had moderate or severe otalgia (a lot of ear tugging; i.e. a score of 2), temperature \>=39°C, or an AOM-SOS scale score \>6 on Day 1 of the episode. If not probably severe, then the episode is categorized as probably nonsevere.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children having at least one episode of AOM.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Surgical Management | The Distribution of AOM Episodes Categorized as Probably Severe or Probably Nonsevere | Probably severe | 156 Episodes of AOM |
| Surgical Management | The Distribution of AOM Episodes Categorized as Probably Severe or Probably Nonsevere | Probably nonsevere | 180 Episodes of AOM |
| Non-Surgical Management | The Distribution of AOM Episodes Categorized as Probably Severe or Probably Nonsevere | Probably severe | 165 Episodes of AOM |
| Non-Surgical Management | The Distribution of AOM Episodes Categorized as Probably Severe or Probably Nonsevere | Probably nonsevere | 168 Episodes of AOM |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of episodes categorized as probably severe.95% CI: [0.76, 1.09]
Secondary
The Distribution of AOM Episodes Presenting With Tympanic Membrane Bulging or Otorrhea
The presence of either tympanic membrane bulging or tympanic membrane perforation with purulent otorrhea, in addition to documentation of symptoms, is required for each episode of AOM.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children having at least one episode of AOM.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Surgical Management | The Distribution of AOM Episodes Presenting With Tympanic Membrane Bulging or Otorrhea | Episodes presenting with tympanic membrane bulging | 86 Episodes of AOM |
| Surgical Management | The Distribution of AOM Episodes Presenting With Tympanic Membrane Bulging or Otorrhea | Episodes presenting with otorrhea | 250 Episodes of AOM |
| Non-Surgical Management | The Distribution of AOM Episodes Presenting With Tympanic Membrane Bulging or Otorrhea | Episodes presenting with tympanic membrane bulging | 248 Episodes of AOM |
| Non-Surgical Management | The Distribution of AOM Episodes Presenting With Tympanic Membrane Bulging or Otorrhea | Episodes presenting with otorrhea | 85 Episodes of AOM |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of episodes presenting with tympanic membrane bulging rather than otorrhea95% CI: [0.26, 0.44]
Secondary
The Distribution of Children Experiencing Treatment Failure (TF)
Parents used the Acute Otitis Media Severity of Symptoms (AOM-SOS) scale (version 4.0) to rate each of 5 symptoms as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Total scores range from 0 to 10; higher scores indicate greater severity of symptoms. AOM episodes were categorized as likely severe if the parent described the child as having moderate or severe otalgia (a lot of ear tugging), temperature ≥39°C, or an AOM-SOS scale score \>6 Day 1 of the episode. TF is defined as frequent AOM recurrences (2 in 3 months, 3 in 6 or 4 in 12); ≥3 likely severe AOM recurrences, receipt of ≥45 cumulative days of systemic antimicrobial treatment for AOM, otorrhea for ≥45 cumulative days or diarrhea associated with antimicrobial treatment for ≥30 cumulative days, respectively, in 12 months; persistent effusion for ≥12 successive months; TM perforation for ≥90 days; AOM related hospitalization; anesthesia reactions; and tubes in children randomized to nonsurgical management.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children with follow-up.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Surgical Management | The Distribution of Children Experiencing Treatment Failure (TF) | Experienced failure | 56 Participants |
| Surgical Management | The Distribution of Children Experiencing Treatment Failure (TF) | Did not experience failure | 68 Participants |
| Non-Surgical Management | The Distribution of Children Experiencing Treatment Failure (TF) | Experienced failure | 74 Participants |
| Non-Surgical Management | The Distribution of Children Experiencing Treatment Failure (TF) | Did not experience failure | 46 Participants |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of children experiencing treatment failure.95% CI: [0.58, 0.92]
Secondary
The Distribution of Children for Whom Diaper Dermatitis Was Reported
Diaper dermatitis is defined as diaper rash necessitating administration of topical antifungal therapy. Adverse events, including diaper dermatitis, were collected from enrollment through the end of study. Each study visit included a review of medication-related adverse events. Any such event that occurred since the previous visit was recorded.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Surgical Management | The Distribution of Children for Whom Diaper Dermatitis Was Reported | Diaper dermatitis was reported | 25 Participants |
| Surgical Management | The Distribution of Children for Whom Diaper Dermatitis Was Reported | Diaper dermatitis was not reported | 104 Participants |
| Non-Surgical Management | The Distribution of Children for Whom Diaper Dermatitis Was Reported | Diaper dermatitis was reported | 33 Participants |
| Non-Surgical Management | The Distribution of Children for Whom Diaper Dermatitis Was Reported | Diaper dermatitis was not reported | 88 Participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of children for whom diaper dermatitis was reported.95% CI: [0.51, 1.22]
Secondary
The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported
PDD is defined as the occurrence of three or more watery stools on 1 day or two or more watery stools on each of 2 consecutive days. Adverse events, including PDD, were collected from enrollment through the end of study. Each study visit included a review of medication-related adverse events. Any such event that occurred since the previous visit was recorded.
Time frame: Day 1 until Day 786.
Population: The analysis was intention-to-treat (ITT). The participants are randomized children.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Surgical Management | The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported | PDD was reported | 21 Participants |
| Surgical Management | The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported | PDD was not reported | 108 Participants |
| Non-Surgical Management | The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported | PDD was reported | 34 Participants |
| Non-Surgical Management | The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported | PDD was not reported | 87 Participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of children for whom PDD was reported.95% CI: [0.44, 1.03]
Secondary
The Distribution of Children for Whom Tube Otorrhea Was Reported
Adverse events, including tube-associated otorrhea, were collected from enrollment through the end of study. Each study visit included a review of adverse events. Any such event that occurred since the previous visit was recorded.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Surgical Management | The Distribution of Children for Whom Tube Otorrhea Was Reported | Tube otorrhea was reported | 94 Participants |
| Surgical Management | The Distribution of Children for Whom Tube Otorrhea Was Reported | Tube otorrhea was not reported | 35 Participants |
| Non-Surgical Management | The Distribution of Children for Whom Tube Otorrhea Was Reported | Tube otorrhea was reported | 34 Participants |
| Non-Surgical Management | The Distribution of Children for Whom Tube Otorrhea Was Reported | Tube otorrhea was not reported | 87 Participants |
Comparison: Null hypothesis: There is no difference between the two groups regarding the proportion of children for whom tube otorrhea was reported.95% CI: [1.91, 3.48]
Secondary
The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment
Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae and ß-lactamase-positive Haemophilus influenzae. Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of \>1 μg/mL.
Time frame: Day 1 until Day 786.
Population: Children with a nasopharyngeal or throat culture at enrollment and at least 1 follow-up nasopharyngeal or throat culture
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | Positive for at least 1 penicillin-nonsusceptible pathogen at enrollment | No penicillin-nonsusceptible isolate at a follow-up visit | 5 Participants |
| Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | No pathogens at enrollment | Penicillin-nonsusceptible isolate at a follow-up visit | 25 Participants |
| Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | No pathogens at enrollment | No penicillin-nonsusceptible isolate at a follow-up visit | 12 Participants |
| Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | Positive only for at least 1 penicillin-susceptible pathogen at enrollment | Penicillin-nonsusceptible isolate at a follow-up visit | 22 Participants |
| Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | Positive only for at least 1 penicillin-susceptible pathogen at enrollment | No penicillin-nonsusceptible isolate at a follow-up visit | 11 Participants |
| Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | Positive for at least 1 penicillin-nonsusceptible pathogen at enrollment | Penicillin-nonsusceptible isolate at a follow-up visit | 38 Participants |
| Non-Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | Positive only for at least 1 penicillin-susceptible pathogen at enrollment | No penicillin-nonsusceptible isolate at a follow-up visit | 15 Participants |
| Non-Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | Positive for at least 1 penicillin-nonsusceptible pathogen at enrollment | No penicillin-nonsusceptible isolate at a follow-up visit | 9 Participants |
| Non-Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | Positive only for at least 1 penicillin-susceptible pathogen at enrollment | Penicillin-nonsusceptible isolate at a follow-up visit | 20 Participants |
| Non-Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | No pathogens at enrollment | Penicillin-nonsusceptible isolate at a follow-up visit | 24 Participants |
| Non-Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | Positive for at least 1 penicillin-nonsusceptible pathogen at enrollment | Penicillin-nonsusceptible isolate at a follow-up visit | 34 Participants |
| Non-Surgical Management | The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment | No pathogens at enrollment | No penicillin-nonsusceptible isolate at a follow-up visit | 11 Participants |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of children with no pathogens at enrollment having a penicillin-nonsusceptible nasopharyngeal or throat isolate at some follow-up visit.95% CI: [0.74, 1.24]
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of children positive only for at least 1 penicillin-susceptible pathogen at enrollment having a penicillin-nonsusceptible nasopharyngeal or throat isolate at some follow-up visit.95% CI: [0.83, 1.72]
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of children positive for at least 1 penicillin nonsusceptible pathogen at enrollment having a penicillin-nonsusceptible nasopharyngeal or throat isolate at some follow-up visit.95% CI: [0.94, 1.29]
Secondary
The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at AOM Episodes Late During the Respiratory Season (April-May)
Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (S. pn) and ß-lactamase-positive Haemophilus influenzae (H. flu). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of \>1 μg/mL.
Time frame: April 1 to May 31, each of the 2 years of follow-up. The mean length of follow-up was 111 days / 3.7 months.
Population: The analysis was ITT. The participants are randomized children with at least one episode of AOM late during the respiratory season (April-May) at which a nasopharyngeal or throat culture is obtained
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at AOM Episodes Late During the Respiratory Season (April-May) | Any nonsusceptible pathogen (nonsusceptible S. pn and/or Beta-lactamase positive H. flu) | 16 Episodes of AOM |
| Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at AOM Episodes Late During the Respiratory Season (April-May) | No nonsusceptible pathogen | 21 Episodes of AOM |
| Non-Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at AOM Episodes Late During the Respiratory Season (April-May) | Any nonsusceptible pathogen (nonsusceptible S. pn and/or Beta-lactamase positive H. flu) | 16 Episodes of AOM |
| Non-Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at AOM Episodes Late During the Respiratory Season (April-May) | No nonsusceptible pathogen | 27 Episodes of AOM |
95% CI: [0.69, 1.95]
Secondary
The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Episodes of AOM
Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (S. pn) and ß-lactamase-positive Haemophilus influenzae (H. flu). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of \>1 μg/mL.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children with at least one episode of AOM at which a nasopharyngeal or throat culture is obtained.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Episodes of AOM | Any nonsusceptible pathogen (nonsusceptible S. pn and/or Beta-lactamase positive H. flu) | 66 Episodes of AOM |
| Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Episodes of AOM | No nonsusceptible pathogen | 107 Episodes of AOM |
| Non-Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Episodes of AOM | Any nonsusceptible pathogen (nonsusceptible S. pn and/or Beta-lactamase positive H. flu) | 64 Episodes of AOM |
| Non-Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Episodes of AOM | No nonsusceptible pathogen | 132 Episodes of AOM |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of episodes of AOM at which a nonsusceptible pathogen is recovered.95% CI: [0.84, 1.55]
Secondary
The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Routine Non-Illness Visits
Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (S. pm) and ß-lactamase-positive Haemophilus influenzae (H. flu). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of \<0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of \>1 μg/mL.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children with at least one routine non-illness visit at which a nasopharyngeal or throat culture is obtained.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Routine Non-Illness Visits | Any nonsusceptible pathogen (nonsusceptible S. pn and/or Beta-lactamase positive H. flu) | 116 Routine non-illness visits |
| Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Routine Non-Illness Visits | No nonsusceptible pathogen | 369 Routine non-illness visits |
| Non-Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Routine Non-Illness Visits | Any nonsusceptible pathogen (nonsusceptible S. pn and/or Beta-lactamase positive H. flu) | 98 Routine non-illness visits |
| Non-Surgical Management | The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Routine Non-Illness Visits | No nonsusceptible pathogen | 349 Routine non-illness visits |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of routine non-illness visits at which a nonsusceptible pathogen is recovered.95% CI: [0.84, 1.41]
Secondary
The Distribution of Parent Reports Indicating At Least One Health Care Encounter Since the Previous Study Visit as an Indicator of Medical Resource Use
Health care encounters, indicators of medical resource use, were ascertained from parent reports. At scheduled study visits, every 8 weeks after randomization. and at interim sick study visits, parents were asked about encounters with healthcare providers, including hospitalizations and visits to emergency departments, urgent care, and primary care providers, since the previous study visit.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children having at least one parent report.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Surgical Management | The Distribution of Parent Reports Indicating At Least One Health Care Encounter Since the Previous Study Visit as an Indicator of Medical Resource Use | Number of reports indicating no health care encounter since the previous study visit | 897 Number of parent reports |
| Surgical Management | The Distribution of Parent Reports Indicating At Least One Health Care Encounter Since the Previous Study Visit as an Indicator of Medical Resource Use | Number of reports indicating at least one health care encounter since the previous study visit | 738 Number of parent reports |
| Non-Surgical Management | The Distribution of Parent Reports Indicating At Least One Health Care Encounter Since the Previous Study Visit as an Indicator of Medical Resource Use | Number of reports indicating no health care encounter since the previous study visit | 956 Number of parent reports |
| Non-Surgical Management | The Distribution of Parent Reports Indicating At Least One Health Care Encounter Since the Previous Study Visit as an Indicator of Medical Resource Use | Number of reports indicating at least one health care encounter since the previous study visit | 672 Number of parent reports |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of parent reports indicating at least one health care encounter since the previous study visit.95% CI: [0.98, 1.18]
Secondary
The Distribution of Reported Occurrences of a Parent Missing Work Due to Child's Illness, as an Indicator of Non-Medical Resource Use
Occurrences of parent missing work due to child's illness, an indicator of non-medical resource use, was ascertained from parent reports at scheduled study visits, every 8 weeks after randomization, and at interim sick study visits.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children having at least one parent report.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Surgical Management | The Distribution of Reported Occurrences of a Parent Missing Work Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports indicating a parent missed work due to child's illness | 286 Number of parent reports |
| Surgical Management | The Distribution of Reported Occurrences of a Parent Missing Work Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports indicating parent did not miss work due to child's illness | 1317 Number of parent reports |
| Surgical Management | The Distribution of Reported Occurrences of a Parent Missing Work Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports for which the parent did not answer the question | 32 Number of parent reports |
| Non-Surgical Management | The Distribution of Reported Occurrences of a Parent Missing Work Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports indicating a parent missed work due to child's illness | 256 Number of parent reports |
| Non-Surgical Management | The Distribution of Reported Occurrences of a Parent Missing Work Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports indicating parent did not miss work due to child's illness | 1342 Number of parent reports |
| Non-Surgical Management | The Distribution of Reported Occurrences of a Parent Missing Work Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports for which the parent did not answer the question | 30 Number of parent reports |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of parent reports indicating a parent missed work due to child's illness.95% CI: [0.88, 1.41]
Secondary
The Distribution of Reported Occurrences of the Need for Special Childcare Arrangements Due to Child's Illness, as an Indicator of Non-Medical Resource Use
Occurrences of the need for special childcare arrangements due to child's illness, an indicator of non-medical resource use, was ascertained from parent reports at scheduled study visits, every 8 weeks after randomization, and at interim sick study visits.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children having at least one parent report.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Surgical Management | The Distribution of Reported Occurrences of the Need for Special Childcare Arrangements Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports indicating the need for special child care arrangements due to child's illness | 231 Number of parent reports |
| Surgical Management | The Distribution of Reported Occurrences of the Need for Special Childcare Arrangements Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports indicating no need for special child care arrangements due to child's illness | 1402 Number of parent reports |
| Surgical Management | The Distribution of Reported Occurrences of the Need for Special Childcare Arrangements Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports for which the parent did not answer the question | 2 Number of parent reports |
| Non-Surgical Management | The Distribution of Reported Occurrences of the Need for Special Childcare Arrangements Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports indicating the need for special child care arrangements due to child's illness | 195 Number of parent reports |
| Non-Surgical Management | The Distribution of Reported Occurrences of the Need for Special Childcare Arrangements Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports indicating no need for special child care arrangements due to child's illness | 1429 Number of parent reports |
| Non-Surgical Management | The Distribution of Reported Occurrences of the Need for Special Childcare Arrangements Due to Child's Illness, as an Indicator of Non-Medical Resource Use | Number of reports for which the parent did not answer the question | 4 Number of parent reports |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of parent reports indicating the need for special childcare arrangements due to child's illness.95% CI: [0.89, 1.48]
Secondary
The Frequency Distribution of AOM Episodes Among Children Completing the Study
An episode of AOM is considered a discrete occurrence if symptoms and signs persisted for, or recurred, 17 or more days after the start of antimicrobial treatment. Children with at least 23 months of follow-up were considered to have completed the study.
Time frame: Day 1 until Day 786. For children completing the study, the mean length of follow-up was 726 days.
Population: The analysis was ITT. The participants are randomized children having follow-up greater than or equal to 23 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Surgical Management | The Frequency Distribution of AOM Episodes Among Children Completing the Study | Number of cumulative episodes = 3 or 4 | 24 Participants |
| Surgical Management | The Frequency Distribution of AOM Episodes Among Children Completing the Study | Number of cumulative episodes = 0 | 17 Participants |
| Surgical Management | The Frequency Distribution of AOM Episodes Among Children Completing the Study | Number of cumulative episodes >= 5 | 26 Participants |
| Surgical Management | The Frequency Distribution of AOM Episodes Among Children Completing the Study | Number of cumulative episodes = 1 or 2 | 41 Participants |
| Non-Surgical Management | The Frequency Distribution of AOM Episodes Among Children Completing the Study | Number of cumulative episodes >= 5 | 18 Participants |
| Non-Surgical Management | The Frequency Distribution of AOM Episodes Among Children Completing the Study | Number of cumulative episodes = 3 or 4 | 29 Participants |
| Non-Surgical Management | The Frequency Distribution of AOM Episodes Among Children Completing the Study | Number of cumulative episodes = 1 or 2 | 41 Participants |
| Non-Surgical Management | The Frequency Distribution of AOM Episodes Among Children Completing the Study | Number of cumulative episodes = 0 | 12 Participants |
Comparison: Null hypothesis: There is no difference between the two groups in the proportion of children completing the study with 0, 1 or 2, 3 or 4, greater than or equal to 5 episodes of AOM.~.p-value: 0.48Chi-squared
Secondary
The Mean Days Per Year Children Experience AOM Symptoms With an Intact Tympanic Membrane (TM)
For a given child, if a day of follow-up coincides with a study visit, the status of the right and left TMs are recorded at the ear exam. If a day of follow-up does not coincide with a study visit the status of each TM is assumed to be the same as the status on the prior day. Scores are used from the 5-item Acute Otitis Media Severity of Symptoms (AOM-SOS) scale (version 4.0) in which parents are asked to rate symptoms, as compared with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Total scores range from 0 to 10, with higher scores indicating greater severity of symptoms. Scores are recorded at study visits and on diaries. The total number of days with an intact TM and a AOM-SOS score greater than or equal to 1 is divided by the total number of years of follow-up to arrive at the days per year with AOM symptoms and an intact TM.
Time frame: Day 1 until Day 786. The mean length of follow-up was 662 days / 1.8 years.
Population: The analysis was ITT. The participants are randomized children.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Surgical Management | The Mean Days Per Year Children Experience AOM Symptoms With an Intact Tympanic Membrane (TM) | 2.00 Days per year | Standard Error 0.29 |
| Non-Surgical Management | The Mean Days Per Year Children Experience AOM Symptoms With an Intact Tympanic Membrane (TM) | 8.33 Days per year | Standard Error 0.59 |
Comparison: Null hypothesis: There is no difference between the two groups in the mean days per year children experience AOM symptoms with an intact TM. The analysis uses a weighted regression model with weights equal to the length of follow-up.95% CI: [-7.55, -5.1]
Secondary
The Mean Days Per Year Children Experience Tube Otorrhea
Adverse events, including tube-associated otorrhea, were collected from enrollment through the end of study. Each study visit included a review of adverse events. Any such event that occurred since the previous visit was recorded, including the date of onset and the date of resolution. For each child, the days per year of tube otorrhea is calculated by dividing the total number of days of tube otorrhea (based on dates of onset and resolution) by the total number of years of follow-up.
Time frame: Day 1 until Day 786. The mean length of follow-up was 662 days / 1.8 years.
Population: The analysis was ITT. The participants are randomized children.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Surgical Management | The Mean Days Per Year Children Experience Tube Otorrhea | 7.96 Days per year | Standard Error 1.1 |
| Non-Surgical Management | The Mean Days Per Year Children Experience Tube Otorrhea | 2.83 Days per year | Standard Error 0.78 |
Comparison: Null hypothesis: There is no difference between the two groups in the mean days per year children experience tube otorrhea. The analysis uses a weighted regression model with weights equal to the length of follow-up.95% CI: [2.6, 7.82]
Secondary
The Mean Days Per Year Children Receive Systemic Antimicrobials for AOM
Systemic antibiotics include Amoxicillin-Clavulanate, Ceftriaxone, Cefdinir, Amoxicillin, Azithromycin, Clindamycin, Levofloxacin, Bactrim, Cefprozil, Omnicef and Trimethoprim-Sulfamethoxazole. The days per year, for each child, is calculated by dividing the total number of days the child receives systemic antimicrobials for AOM (based on the recorded start and stop dates) by the total number of years of follow-up.
Time frame: Day 1 until Day 786. The mean length of follow-up was 662 days / 1.8 years.
Population: The analysis was ITT. The participants are randomized children.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Surgical Management | The Mean Days Per Year Children Receive Systemic Antimicrobials for AOM | 8.76 Days per year | Standard Error 0.94 |
| Non-Surgical Management | The Mean Days Per Year Children Receive Systemic Antimicrobials for AOM | 12.92 Days per year | Standard Error 0.9 |
Comparison: Null hypothesis: There is no difference between the two groups in the mean days per year children receive systemic antimicrobials for AOM. The analysis uses a weighted regression model with weights equal to the length of follow-up.95% CI: [-6.82, -2.18]
Secondary
The Mean Score Representing Parental Satisfaction With Clinical Management
At the end-of-study visit, parents were asked to rate their level of satisfaction with their child's assigned management using a 5-point scale with higher numbers indicating greater satisfaction, specifically 1 = very dissatisfied, 2 = somewhat dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = somewhat satisfied, and 5 = very satisfied.
Time frame: The end-of-study visit. The mean day for this visit was 726.
Population: The analysis was ITT. The participants are randomized children who completed the study and whose parent rated their level of satisfaction.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Surgical Management | The Mean Score Representing Parental Satisfaction With Clinical Management | 4.64 Score on a scale | Standard Error 0.1 |
| Non-Surgical Management | The Mean Score Representing Parental Satisfaction With Clinical Management | 4.43 Score on a scale | Standard Error 0.13 |
Comparison: Null hypothesis: There is no difference between the two groups in the mean parental satisfaction score95% CI: [-0.06, 0.56]
Secondary
The Mean Scores on the 6 Item Caregiver Impact Questionnaire (CIQ)
The Caregiver Impact Questionnaire (CIQ) is a 6 item assessment addressing lack of sleep, absence from work or education, canceling of family activities, changing daily activities, feeling nervous and feeling helpless. Each of these responses is expanded to a continuous scale from 0 (no impact on caregiver) to 100 (greatest impact). The average response, i.e., score, for these 6 items is calculated. The overall caregiver's quality of life (QOL) score, also captured on the CIQ, is expressed on a ordinal response scale that ranges from 0 (worst quality of life) to 10 (best quality). The CIQ is administered to the parent every 16 weeks after randomization and occasionally at sick visits.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children having at least one parent report.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Surgical Management | The Mean Scores on the 6 Item Caregiver Impact Questionnaire (CIQ) | Caregiver impact questionnaire score | 10.82 Score on a scale | Standard Error 0.53 |
| Surgical Management | The Mean Scores on the 6 Item Caregiver Impact Questionnaire (CIQ) | Caregiver impact questionnaire--Caregiver's overall QOL score | 8.55 Score on a scale | Standard Error 0.06 |
| Non-Surgical Management | The Mean Scores on the 6 Item Caregiver Impact Questionnaire (CIQ) | Caregiver impact questionnaire score | 10.93 Score on a scale | Standard Error 0.55 |
| Non-Surgical Management | The Mean Scores on the 6 Item Caregiver Impact Questionnaire (CIQ) | Caregiver impact questionnaire--Caregiver's overall QOL score | 8.50 Score on a scale | Standard Error 0.06 |
Comparison: Null hypothesis: There is no difference between the two groups in the mean caregiver impact questionnaire score.95% CI: [-1.55, 1.47]
Comparison: Null hypothesis: There is no difference between the two groups in the mean caregiver impact questionnaire--caregiver's overall QOL score.95% CI: [-0.14, 0.2]
Secondary
The Mean Scores on the 6 Item Quality of Life Survey Questionnaire (OM-6)
The OM-6 is a 6 item quality of life assessment addressing physical suffering, hearing loss, speech impairment, emotional distress, activity limitations and caregiver concerns. Responses are regarded on an ordinal scale ranging from 1 (no problem) to 7 (greatest problem). The average response, i.e., score, for these 6 items is calculated. The overall child's quality of life (QOL) score, also captured on the OM-6, is expressed on an ordinal response scale that ranges from 0 (worst quality of life) to 10 (best quality). A OM-6 is administered to the parent every 16 weeks after randomization and occasionally at sick visits.
Time frame: Day 1 until Day 786.
Population: The analysis was ITT. The participants are randomized children having at least one parent report.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Surgical Management | The Mean Scores on the 6 Item Quality of Life Survey Questionnaire (OM-6) | OM-6 survey score | 1.5 Score on a scale | Standard Error 0.03 |
| Surgical Management | The Mean Scores on the 6 Item Quality of Life Survey Questionnaire (OM-6) | OM-6 survey--Children's overall QOL score | 8.45 Score on a scale | Standard Error 0.07 |
| Non-Surgical Management | The Mean Scores on the 6 Item Quality of Life Survey Questionnaire (OM-6) | OM-6 survey score | 1.55 Score on a scale | Standard Error 0.03 |
| Non-Surgical Management | The Mean Scores on the 6 Item Quality of Life Survey Questionnaire (OM-6) | OM-6 survey--Children's overall QOL score | 8.37 Score on a scale | Standard Error 0.07 |
Comparison: Null hypothesis: There is no difference between the two groups in the mean OM-6 survey score95% CI: [-0.13, 0.02]
Comparison: Null hypothesis: There is no difference between the two groups in the mean OM-6 survey--children's overall QOL score.95% CI: [-0.13, 0.24]
Secondary
The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year According to the Estimated Risk of Acute Otitis Media (AOM) Recurrences at Enrollment
An episode of AOM is considered a discrete occurrence if symptoms and signs persisted for, or recurred, \>=17 days after the start of antimicrobial treatment. The rate is calculated by dividing the total # of occurrences by the total # of years of follow-up. Risk of recurrences was based on early age of onset of AOM; numerous and/or frequent previous AOM episodes; receipt of multiple courses of antibiotic; eligibility for enrollment first evident during warm-weather months; parental characterization of previous AOM episodes as severe; eligibility for enrollment despite nonexposure to other young children; moderate or marked tympanic membrane (TM) bulging with previous AOM episodes; most previous AOM episodes in both ears; and a high score on the Acute Otitis Media Severity of Symptom scale (with scores ranging from 0 to 10 and higher scores indicating greater severity of symptoms) during screening and/or at enrollment. Multiple imputation was used when follow-up was incomplete.
Time frame: Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years. For each child with incomplete 2-year follow-up, multiple imputation was used and values for the remaining days/years were imputed.
Population: The analysis was ITT. The participants are randomized children. For each child with incomplete 2-year follow-up, the total number of episodes of acute otitis media were imputed using multivariate imputation by chained equations with 50 imputations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Surgical Management | The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year According to the Estimated Risk of Acute Otitis Media (AOM) Recurrences at Enrollment | Children considered at low risk of AOM recurrence | 1.28 Occurrences per child-year | Standard Error 0.1 |
| Surgical Management | The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year According to the Estimated Risk of Acute Otitis Media (AOM) Recurrences at Enrollment | Children considered at high risk of AOM recurrence | 1.67 Occurrences per child-year | Standard Error 0.11 |
| Non-Surgical Management | The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year According to the Estimated Risk of Acute Otitis Media (AOM) Recurrences at Enrollment | Children considered at low risk of AOM recurrence | 1.56 Occurrences per child-year | Standard Error 0.1 |
| Non-Surgical Management | The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year According to the Estimated Risk of Acute Otitis Media (AOM) Recurrences at Enrollment | Children considered at high risk of AOM recurrence | 1.56 Occurrences per child-year | Standard Error 0.13 |
Comparison: Null hypothesis: There is no difference between the two groups in the rate of occurrence of AOM per child-year during the 2 year follow-up among children considered at low risk of AOM recurrences at enrollment..95% CI: [0.67, 1.01]
Comparison: Null hypothesis: There is no difference between the two groups in the rate of occurrence of AOM per child-year during the 2 year follow-up among children considered at high risk of AOM recurrences at enrollment.95% CI: [0.86, 1.33]
Comparison: Null hypothesis: There is no interaction between comparison group (Surgical Management, Non-Surgical Management) and risk group (children considered at low risk of AOM recurrences at enrollment, children considered at high risk of AOM recurrences at enrollment).p-value: 0.08Generalized linear models
Secondary
The Time to the First Episode of AOM
The time to the first episode of AOM is defined as the time, expressed in months, from randomization until the first episode of AOM.
Time frame: Day 1 until Day 786. The mean length of follow-up was 662 days / 21.8 months.
Population: The analysis was ITT. The participants are randomized children.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Surgical Management | The Time to the First Episode of AOM | 4.34 Months |
| Non-Surgical Management | The Time to the First Episode of AOM | 2.33 Months |
Comparison: Null hypothesis: There is no difference between the two groups regarding the time to the first episode of AOM.95% CI: [0.52, 0.9]
Secondary
The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness
Total costs in US dollars were calculated by summing costs of lost wages, office visits, medical procedures, hospitalizations, and medications. Total QALDs were calculated by summing daily utility values. A utility value of 1.0 was assumed for days without AOM, otorrhea, or hospitalization. For days where these states were reported, published utility values associated with each state were used. To arrive at the final measure, total costs were divided by total utility values.
Time frame: Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years.
Population: The analysis was ITT. The participants are randomized children.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Surgical Management | The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness | 7.19 US dollars per quality adjusted life day |
| Non-Surgical Management | The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness | 5.79 US dollars per quality adjusted life day |
Secondary
The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness According to the Estimated Risk of Acute Otitis Media Recurrences at Enrollment
Total costs in US dollars were calculated by summing costs of lost wages, office visits, medical procedures, hospitalizations, and medications. Total QALDs were calculated by summing daily utility values. A utility value of 1.0 was assumed for days without AOM, otorrhea, or hospitalization. For days where these states were reported, published utility values associated with each state were used. To arrive at the final measure, total costs were divided by total utility values. The estimated risk of AOM at enrollment is described under both Baseline Characteristics and Outcome Measure #2.
Time frame: Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years.
Population: The analysis was ITT. The participants are randomized children.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Surgical Management | The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness According to the Estimated Risk of Acute Otitis Media Recurrences at Enrollment | Children considered at low risk of AOM recurrence | 6.25 US dollars per quality adjusted life day |
| Surgical Management | The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness According to the Estimated Risk of Acute Otitis Media Recurrences at Enrollment | Children considered at high risk of AOM recurrence | 8.00 US dollars per quality adjusted life day |
| Non-Surgical Management | The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness According to the Estimated Risk of Acute Otitis Media Recurrences at Enrollment | Children considered at low risk of AOM recurrence | 5.70 US dollars per quality adjusted life day |
| Non-Surgical Management | The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness According to the Estimated Risk of Acute Otitis Media Recurrences at Enrollment | Children considered at high risk of AOM recurrence | 5.91 US dollars per quality adjusted life day |