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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 (Responsible Party):
Alejandro Hoberman, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00377260
First received: September 14, 2006
Last updated: October 24, 2016
Last verified: October 2016
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
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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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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.
No text entered.

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 
Overall Participants Analyzed 
[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]
Count of Participants
     
Female      69  47.9%      67  45.6%      136  46.7% 
Male      75  52.1%      80  54.4%      155  53.3% 
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 
[1] AOM pathogens refer to Streptococcus Pneumoniae, Haemophilus Influenzae, Moraxella Catarrhalis or Streptococcus Pyogenes
Degree of tympanic membrane bulging [1] 
[Units: Participants]
     
Slight   42   39   81 
Moderate   63   70   133 
Marked   39   38   77 
[1] 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.
Ethnicity [1] 
[Units: Participants]
     
Hispanic   21   19   40 
Non-Hispanic   123   128   251 
[1] Parents were asked if their child is Hispanic.
Exposed to other children [1] 
[Units: Participants]
     
Exposed   69   72   141 
Not exposed   75   75   150 
[1]

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.

Health insurance status [1] 
[Units: Participants]
     
Private   43   42   85 
Medicaid   98   103   201 
None   3   2   5 
[1] Parents were asked the child's health insurance status
History of recurrent acute otitis media [1] 
[Units: Participants]
     
Yes   21   29   50 
No   123   118   241 
[1]

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".

Laterality of Acute Otitis Media [1] 
[Units: Participants]
     
Bilateral   75   77   152 
Unilateral   69   70   139 
[1] 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.
Maternal Education [1] 
[Units: Participants]
     
Less than high school   24   16   40 
High school graduate   90   95   185 
College graduate   30   35   65 
Unknown   0   1   1 
[1] Parents were asked about the highest level of maternal education.
Race [1] 
[Units: Participants]
     
Caucasian   66   65   131 
African-American   62   58   120 
Other   16   24   40 
[1] 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.
Severity of symptoms score [1] 
[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 
[1]

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 minimum score is 3, the maximum is 14.

Study Site [1] 
[Units: Participants]
     
Children's Hospital of Pittsburgh (Pittsburgh, PA)   113   117   230 
Armstrong Pediatrics (Kittanning, PA)   31   30   61 
[1] Children's Hospital of Pittsburgh (CHP) is the Primary Care Center of CHP. Armstrong Pediatrics is a large community practice in Kittanning, PA.
Mean Estimated Probability of Middle Ear Effusion [1] 
[Units: Probability of effusion]
Mean (Standard Deviation)
     
Right ear   .42  (.31)   .39  (.27)   .41  (.29) 
Left ear   .35  (.30)   .44  (.29)   .40  (.30) 
[1] 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.
Mean score of AOM-SOS [1] 
[Units: AOM-SOS score]
Mean (Standard Deviation)
 7.69  (2.85)   7.90  (2.87)   7.80  (2.86) 
[1]

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 minimum 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 ]

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 ]

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 ]

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. ]

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. ]

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 ]

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 ]

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 ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]

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. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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.


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


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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Alejandro Hoberman, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00377260     History of Changes
Other Study ID Numbers: 05-0142
U01AI066007 ( US NIH Grant/Contract Award Number )
Study First Received: September 14, 2006
Results First Received: April 13, 2010
Last Updated: October 24, 2016
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board