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Acute Otitis Media (AOM) Therapy Trial in Young Children

This study has been completed.
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00377260
First received: September 14, 2006
Last updated: February 23, 2011
Last verified: February 2011
History of Changes
Results First Received: April 13, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Acute Otitis Media
Interventions: Drug: Amoxicillin-clavulanate
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Amoxicillin-Clavulanate Reconstituted amoxicillin-clavulanate at 90/6.4 mg/kg/day in 2 divided doses for 10 days.
Placebo Reconstituted placebo in 2 divided doses for 10 days.

Participant Flow:   Overall Study
    Amoxicillin-Clavulanate     Placebo  
STARTED     144     147  
COMPLETED     142 [1]   142 [1]
NOT COMPLETED     2     5  
Lost to Follow-up                 0                 1  
Withdrawal by Subject                 2                 4  
[1] A child is considered a completer if he/she had at least one visit after the end of therapy.



  Baseline Characteristics
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Reporting Groups
  Description
Amoxicillin-Clavulanate Reconstituted amoxicillin-clavulanate at 90/6.4 mg/kg/day in 2 divided doses for 10 days.
Placebo Reconstituted placebo in 2 divided doses for 10 days.
Total Total of all reporting groups

Baseline Measures
    Amoxicillin-Clavulanate     Placebo     Total  
Number of Participants  
[units: participants]
 		  144     147     291  
Age, Customized  
[units: participants]
 		     
6-11 months     83     78     161  
12-17 months     35     42     77  
18-23 months     26     27     53  
Gender  
[units: participants]
 		     
Female     69     67     136  
Male     75     80     155  
Colonization With AOM Pathogens [1]
[units: participants]
 		     
Presence of at least one AOM pathogen     123     119     242  
Absence of any AOM pathogen     16     24     40  
No culture result     5     4     9  
Degree of tympanic membrane bulging [2]
[units: participants]
 		     
Slight     42     39     81  
Moderate     63     70     133  
Marked     39     38     77  
Ethnicity [3]
[units: participants]
 		     
Hispanic     21     19     40  
Non-Hispanic     123     128     251  
Exposed to other children [4]
[units: participants]
 		     
Exposed     69     72     141  
Not exposed     75     75     150  
Health insurance status [5]
[units: participants]
 		     
Private     43     42     85  
Medicaid     98     103     201  
None     3     2     5  
History of recurrent acute otitis media [6]
[units: participants]
 		     
Yes     21     29     50  
No     123     118     241  
Laterality of Acute Otitis Media [7]
[units: participants]
 		     
Bilateral     75     77     152  
Unilateral     69     70     139  
Maternal Education [8]
[units: participants]
 		     
Less than high school     24     16     40  
High school graduate     90     95     185  
College graduate     30     35     65  
Unknown     0     1     1  
Race [9]
[units: participants]
 		     
Caucasian     66     65     131  
African-American     62     58     120  
Other     16     24     40  
Severity of symptoms score [10]
[units: participants]
 		     
Score of 3-5     37     33     70  
Score of 6-8     46     51     97  
Score of 9-11     46     44     90  
Score of 12-14     15     19     34  
Study Site [11]
[units: participants]
 		     
Children's Hospital of Pittsburgh (Pittsburgh, PA)     113     117     230  
Armstrong Pediatrics (Kittanning, PA)     31     30     61  
Mean Estimated Probability of Middle Ear Effusion [12]
[units: probability of effusion]
Mean ± Standard Deviation 		     
Right ear     .42  ± .31     .39  ± .27     .41  ± .29  
Left ear     .35  ± .30     .44  ± .29     .40  ± .30  
Mean score of AOM-SOS [13]
[units: AOM-SOS score]
Mean ± Standard Deviation 		  7.69  ± 2.85     7.90  ± 2.87     7.80  ± 2.86  
[1] AOM pathogens refer to Streptococcus Pneumoniae, Haemophilus Influenzae, Moraxella Catarrhalis or Streptococcus Pyogenes
[2] The degree of bulging for the ear with the greater level of bulging at entry is summarized. The otoscopists rated this as slight bulging, moderate bulging or marked bulging. The otoscopists have all been validated for inter-observer reliability.
[3] Parents were asked if their child is Hispanic.
[4]

Exposed to other children is defined as a child being exposed to 3 or more children, including siblings, for at least 10 hours per week.

Not exposed is defined as any child who does not meet this criteria.
[5] Parents were asked the child's health insurance status
[6]

Records were obtained and reviewed for a history of recurrent acute otitis media.

"Yes" indicates that the child had a documented history of at least 3 acute otitis media episodes in the past 6 months or at least 4 episodes in the past year.

"No" indicates that the child did not meet the criteria for "Yes".
[7] Bilateral means that both ears were found to be acute. Unilateral means that only one ear was found to be acute, the other ear could have had middle ear effusion or have been free of middle ear effusion.
[8] Parents were asked about the highest level of maternal education.
[9] Parents were asked what race or races they would use to describe their child. Caucasian and African-American are listed when only one race was given. Other includes other races as well as any who gave more than one race.
[10]

Parents completed the Acute Otitis-Media-Severity of Symptoms (AOM-SOS)scale prior to their child's ear exam. It's a list of 7 symptoms associated with Acute Otitis-media.

[tugging/rubbing/holding ears; crying more; irritable/fussy; difficulty sleeping; less playful/active; eating less; fever or warm to touch. The parent rates these symptoms as No (0 points), A little (1 point) or A lot (2 points). Children must have at least 3 points to qualify, so the minumum score is 3, the maximum is 14.
[11] Children's Hospital of Pittsburgh (CHP) is the Primary Care Center of CHP. Armstrong Pediatrics is a large community practice in Kittanning, PA.
[12] 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.
[13]

This is the mean score for each arm. Parents completed the Acute Otitis Media -Severity of Symptoms (AOM-SOS) scale prior to their child's ear exam. It's a list of 7 symptoms associated with Acute Otitis-media.

[tugging/rubbing/holding ears; crying more; irritable/fussy; difficulty sleeping; less playful/active; eating less; fever or warm to touch. The parent rates these symptoms as No (0 points), A little (1 point) or A lot (2 points). Children must have at least 3 points to qualify, so the minumum score is 3, the maximum is 14.



  Outcome Measures
  Show All Outcome Measures

1.  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 Frame: The first 7 days on therapy ]
  Show Outcome Measure 1

2.  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 Frame: The first 7 days on therapy ]
  Show Outcome Measure 2

3.  Primary:   The Weighted Average Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, According to Treatment Assignment   [ Time Frame: During the first 7 days of therapy ]
  Show Outcome Measure 3

4.  Secondary:   The Distribution of Clinical Failures by the On-therapy Visit According to Treatment Assignment   [ Time Frame: On-therapy visit. The mean day for this visit was 5.0. ]
  Show Outcome Measure 4

5.  Secondary:   The Distribution of Clinical Failures by the End-of-therapy Visit According to Treatment Assignment   [ Time Frame: End-of-therapy visit. The mean day for this visit was 11.6. ]
  Show Outcome Measure 5

6.  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   [ Time Frame: During the first 7 days of therapy ]
  Show Outcome Measure 6

7.  Secondary:   The Distribution of Children Developing Worsening Symptoms Prior to Receiving 72 Hours of Study Medication According to Treatment Assignment   [ Time Frame: Before receiving 72 hours of study medication ]
  Show Outcome Measure 7

8.  Secondary:   The Mean Number of Times Analgesic Medication Was Administered to the Child According to Treatment Assignment   [ Time Frame: The first 10 days of follow-up ]
  Show Outcome Measure 8

9.  Secondary:   The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment   [ 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. ]
  Show Outcome Measure 9

10.  Secondary:   The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens 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. ]
  Show Outcome Measure 10

11.  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. ]
  Show Outcome Measure 11

12.  Secondary:   The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment   [ Time Frame: Follow-up visit. The mean day for this visit was 22.8. ]
  Show Outcome Measure 12

13.  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. ]
  Show Outcome Measure 13

14.  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   [ Time Frame: On-therapy visit. The mean day for this visit was 5.0. ]
  Show Outcome Measure 14

15.  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   [ Time Frame: End-of-therapy visit. The mean day for this visit was 11.6. ]
  Show Outcome Measure 15

16.  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   [ Time Frame: Follow-up visit. The mean day for this visit was 22.8. ]
  Show Outcome Measure 16

17.  Secondary:   The Mean Number of Visits to a Primary Care Provider (PCP) According to Treatment Assignment   [ 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. ]
  Show Outcome Measure 17

18.  Secondary:   The Mean Number of Emergency Room Visits According to Treatment Assignment   [ 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. ]
  Show Outcome Measure 18

19.  Secondary:   The Mean Number of Antibiotic Prescriptions, Exclusive of Study Medication, According to Treatment Assignment   [ 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. ]
  Show Outcome Measure 19

20.  Secondary:   The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Having Missed Work According to Treatment Assignment   [ 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. ]
  Show Outcome Measure 20

21.  Secondary:   The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Making Special Daycare Arrangements According to Treatment Assignment   [ 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. ]
  Show Outcome Measure 21

22.  Secondary:   The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the On-therapy Visit According to Treatment Assignment   [ Time Frame: On-therapy visit. The mean day for this visit was 5.0. ]
  Show Outcome Measure 22

23.  Secondary:   The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded 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. ]
  Show Outcome Measure 23

24.  Secondary:   The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment   [ Time Frame: Follow-up visit. The mean day for this visit was 22.8. ]
  Hide Outcome Measure 24

Measure Type Secondary
Measure Title The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment
Measure Description 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was ITT. The number of participants equals the number of children whose parent reported a satisfaction score at the follow-up visit.

Reporting Groups
  Description
Amoxicillin-Clavulanate Reconstituted amoxicillin-clavulanate at 90/6.4 mg/kg/day in 2 divided doses for 10 days.
Placebo Reconstituted placebo in 2 divided doses for 10 days.

Measured Values
    Amoxicillin-Clavulanate     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  139     139  
The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment  
[units: parental satisfaction score]
Mean ± Standard Deviation 		  4.53  ± 0.89     4.17  ± 1.12  


Statistical Analysis 1 for The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment
Groups [1] All groups
Method [2] Regression, Linear
P Value [3] .005
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Null hypothesis: There is no difference between the groups regarding the mean parental satisfaction score at the follow-visit visit.
[2] Other relevant information, such as adjustments or degrees of freedom:
  The comparison adjusted for site, history of recurrent acute otitis media and exposure to other children.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.




  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Long-term implications of abnormal otoscopic findings (bulging) without symptoms, and persistent middle-ear effusion without findings of acute inflammation as forerunners of subsequent acute otitis media episodes remains uncertain.  


Results Point of Contact:  
Name/Title: Efficacy of Antimicrobials in Young children with Acute Otitis Media
Organization: Children's Hospital of Pittsburgh of UPMC
phone: 412-692-5249
e-mail: Hoberman@chp.edu


No publications provided by University of Pittsburgh

Publications automatically indexed to this study:


Responsible Party: Alejandro Hoberman, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00377260     History of Changes
Other Study ID Numbers: 05-0142, U01AI066007
Study First Received: September 14, 2006
Results First Received: April 13, 2010
Last Updated: February 23, 2011
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board