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Efficacy of Short-Course Antimicrobial Treatment for Children With Acute Otitis Media and Impact on Resistance

This study has been terminated.
(The primary objective of the study was met.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01511107
First Posted: January 18, 2012
Last Update Posted: February 10, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Alejandro Hoberman, University of Pittsburgh
Results First Submitted: September 30, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Acute Otitis Media
Interventions: Drug: Amoxicillin-Clavulanate, 10 days
Drug: Amoxicillin-Clavulanate, 5 days

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Amoxicillin-Clavulanate, 10 Days Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.
Amoxicillin-Clavulanate, 5 Days Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.

Participant Flow:   Overall Study
    Amoxicillin-Clavulanate, 10 Days   Amoxicillin-Clavulanate, 5 Days
STARTED   260 [1]   260 [1] 
COMPLETED   238 [2]   219 [2] 
NOT COMPLETED   22   41 
Ineligible                3                2 
Lost to Follow-up                10                19 
Withdrawal by Subject                9                20 
[1] Randomized to the treatment group.
[2] Completed - Assessed at a final visit in Sep or at the end of the respiratory season in Apr or May.



  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.
520 children underwent randomization; 260 were randomized to the amoxicillin-clavulante 10 days group and 260 to the amoxicillin-clavulante 5 days, placebo 5 days group. 3 and 2, respectively, were found ineligible after randomization and were withdrawn by the PI. The remaining 257 and 258 participants, respectively, were the basis for analysis.

Reporting Groups
  Description
Amoxicillin-Clavulanate, 10 Days Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.
Amoxicillin-Clavulanate, 5 Days Amoxicillin-clavulanate administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.
Total Total of all reporting groups

Baseline Measures
   Amoxicillin-Clavulanate, 10 Days   Amoxicillin-Clavulanate, 5 Days   Total 
Overall Participants Analyzed 
[Units: Participants]
 257   258   515 
Age, Customized 
[Units: Participants]
     
6-11 months   129   132   261 
12-17 months   80   77   157 
18-23 months   48   49   97 
Gender 
[Units: Participants]
Count of Participants
     
Female      115  44.7%      123  47.7%      238  46.2% 
Male      142  55.3%      135  52.3%      277  53.8% 
Ethnicity (NIH/OMB) [1] 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      24   9.3%      23   8.9%      47   9.1% 
Not Hispanic or Latino      233  90.7%      235  91.1%      468  90.9% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0% 
[1] Parents were asked what ethnicity they would use to describe their child.
Race (NIH/OMB) [1] 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0% 
Asian      7   2.7%      5   1.9%      12   2.3% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      110  42.8%      118  45.7%      228  44.3% 
White      116  45.1%      110  42.6%      226  43.9% 
More than one race      21   8.2%      21   8.1%      42   8.2% 
Unknown or Not Reported      3   1.2%      4   1.6%      7   1.4% 
[1] Parents were asked what race or races they would use to describe their child.
Study Site [1] 
[Units: Participants]
     
Children's Hospital of Pittsburgh (CHP)   163   163   326 
Children's Community Pediatrics   47   47   94 
Kentucky Pediatric and Adult Research   47   48   95 
[1] Participating clinical study sites included: Children's Hospital of Pittsburgh (CHP) of University of Pittsburgh Medical Center (UPMC) Primary Care Center - Oakland, CHP of UPMC Emergency Department, Pittsburgh, Pennsylvania (PA); its affiliated University of Pittsburgh Clinical and Translational Science Institute (PittNet) Pediatric Practice-Based Research Network (PBRN) - PittNet North, East, South, City Loop, Pittsburgh, PA and Kittanning, PA; and Kentucky Pediatric/Adult Research (KPAR) and Physicians to Children and Adolescents (PTCA) Bardstown, Kentucky (KY).
Maternal Education [1] 
[Units: Participants]
     
Less than high school   31   26   57 
High school graduate or equivalent   150   169   319 
College graduate   76   62   138 
Unknown   0   1   1 
[1] Parent was asked about the highest level of maternal education. High school graduate or equivalent implies the mother has graduated high school graduate or has a General Education Diploma (GED) or has attended technical school or some college or has an associates degree.
Type of Health Insurance [1] 
[Units: Participants]
     
Private   84   75   159 
Public   171   179   350 
None   2   4   6 
[1] Type of health insurance relates to the child's insurance.
Exposure to Other Children [1] 
[Units: Participants]
     
Not exposed   109   105   214 
Exposed   148   153   301 
[1] Exposed to other children is defined as a being exposed to 3 or more children for 10 or more hours per week or living in a home with at least 3 other children under the age of 18.
Acute Otitis Media Severity of Symptoms (AOM-SOS) Score [1] 
[Units: Participants]
     
3-5   43   59   102 
6-8   75   70   145 
9-11   98   95   193 
12-14   41   34   75 
[1] The AOM-SOS scale measures seven discrete items: tugging of ears, crying, irritability, difficulty sleeping, diminished activity, diminished appetite, and fever. Parents are asked to rate these symptoms in comparison with the child’s usual state, as “none,” “a little,” or “a lot,” with corresponding scores of 0, 1, and 2. Thus, total scores range from 0 to 14, with higher scores indicating greater severity of symptoms. Children must have at least a total score of 3 at enrollment to qualify for the study.
Mean AOM-SOS Score [1] 
[Units: AOM-SOS score]
Mean (Standard Deviation)
 8.6  (2.9)   8.2  (3.0)   8.4  (3.0) 
[1] The AOM-SOS scale measures seven discrete items: tugging of ears, crying, irritability, difficulty sleeping, diminished activity, diminished appetite, and fever. Parents are asked to rate these symptoms in comparison with the child’s usual state, as “none,” “a little,” or “a lot,” with corresponding scores of 0, 1, and 2. Thus, total scores range from 0 to 14, with higher scores indicating greater severity of symptoms.
Estimated severity of illness from pain and fever history only [1] 
[Units: Participants]
     
Likely nonsevere   111   121   232 
Likely severe   146   137   283 
[1] AOM episodes were categorized as “likely severe” if the parent described the child as having had “a lot” of ear tugging or “a lot” of fever during the preceding 24 hours, else the episode was categorized as "likely nonsevere."
Laterality of Acute Otitis Media (AOM) 
[Units: Participants]
     
Unilateral   136   126   262 
Bilateral   121   132   253 
Degree of Tympanic Membrane Bulging [1] 
[Units: Participants]
     
Slight   35   45   80 
Moderate   137   135   272 
Marked   85   78   163 
[1] If a child has unilateral AOM, the degree of bulging reflects the degree of bulging in the ear with AOM. If a child has bilateral AOM, the degree of bulging reflects the degree of bulging in the ear with the greater level of bulging,
Streptococcus Pneumoniae (S pneumoniae) Sensitivity in Nasopharyngeal Cultures [1] 
[Units: Participants]
     
S pneumoniae absent   131   120   251 
S pneumoniae present, susceptible   84   94   178 
S pneumoniae present, intermediate   20   28   48 
S pneumoniae present, resistant   21   16   37 
Unknown, no culture   1   0   1 
[1] Susceptibility to penicillin was determined as follows: When minimum inhibitory concentration (MIC) was available , susceptible was defined as MIC <0.1 µg/mL, intermediate as MIC 0.1 to 1 µg/mL, and resistant as MIC >1 µg/mL. When MIC was not available, susceptible was defined as showing oxacillin disk zone size >20 mm, intermediate as zone size 9 to 20 mm, and resistant as zone size ≤8 mm.
Haemophilus Influenzae (H influenzae) Sensitivity in Nasopharyngeal Cultures [1] 
[Units: Participants]
     
H influenzae absent   172   197   369 
H influenzae present, susceptible   53   37   90 
H influenzae present, nonsusceptible   31   24   55 
Unknown, no culture   1   0   1 
[1] Susceptible was defined as beta-lactamase-negative and E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and E test MIC >1 µg/mL.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   The Distribution of Children Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit Specific to the Index Episode of AOM   [ Time Frame: From 72 hours after randomization until day 21 of the index episode. The mean day for this visit was 13.2. ]

2.  Secondary:   The Distribution of AOM Recurrences Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit   [ Time Frame: From 72 hours after the AOM recurrence was diagnosed until day 21 of the recurrence. The mean day for this visit was 13.3. ]

3.  Secondary:   The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen   [ Time Frame: The day 12-14 visit. The mean day for this visit was 13.3. ]

4.  Secondary:   The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen   [ Time Frame: The day 12-14 visit. The mean day for this visit was 13.4. ]

5.  Secondary:   The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen   [ Time Frame: The day 12-14 visit. The mean day for this visit was 13.2. ]

6.  Secondary:   The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen   [ Time Frame: The day 12-14 visit. The mean day for this visit was 13.9. ]

7.  Secondary:   The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Positive for One or More Nonsusceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen   [ Time Frame: The end-of-treatment visit. The mean day for this visit was 13.6. ]

8.  Secondary:   The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Positive for One or More Nonsusceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen   [ Time Frame: The end-of-treatment visit. The mean day for this visit was 13.4. ]

9.  Secondary:   The Distribution of Children Whose Nasopharyngeal (NP) Isolates at Enrollment Are Pathogen Negative or Positive Only for at Least One Susceptible Pathogen Who Become Colonized With Nonsusceptible Pathogens at Any Time Over the Course of Follow-up   [ Time Frame: Day 1 of study entry until day 365 ]

10.  Secondary:   The Distribution of 6 Week Follow-up, Non-Illness Visits During the Respiratory Season at Which a Nonsusceptible Pathogen is Recovered   [ Time Frame: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive. ]

11.  Secondary:   The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate   [ Time Frame: The day 12-14 visit specific to the index episode. The mean day for this visit was 13.4. ]

12.  Secondary:   The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Streptococcus Pneumoniae (S pn) Isolate   [ Time Frame: The day 12-14 visit following a recurrence. The mean day for this visit was 13.6. ]

13.  Secondary:   The Distribution of Children for Whom the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit, Specific to the Index Episode, Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate   [ Time Frame: The day 12-14 visit specific to the index episode. The mean day for this visit was 13.4. ]

14.  Secondary:   The Distribution of AOM Recurrences for Which the Follow-up Nasopharyngeal (NP) Culture at the Day 12-14 Visit Yields a Nonsusceptible Haemophilus Influenzae (H Flu) Isolate   [ Time Frame: The day 12-14 visit following a recurrence. The mean day for this visit was 13.6. ]

15.  Secondary:   The Distribution of Children With AOM Recurrences and Relapses Within 60 Days of Enrollment   [ Time Frame: Day 1 of study entry until day 60. ]

16.  Secondary:   The Distribution of Children With AOM Recurrences and Relapses Within the Entire Respiratory Season   [ Time Frame: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive. ]

17.  Secondary:   The Mean Rate, Per Month, of Protocol AOM Recurrences and Relapses Within 60 Days of Enrollment   [ Time Frame: Day 1 of study entry until day 60. ]

18.  Secondary:   The Mean Rate, Per Month, of Protocol AOM Recurrences and Relapses Within the Entire Respiratory Season   [ Time Frame: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive. ]

19.  Secondary:   The Mean Number of Days Systemic Antibiotics Were Received During the Entire Respiratory Season   [ Time Frame: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive. ]

20.  Secondary:   The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14   [ Time Frame: From day 6 of administration of study product until day 14 for all episodes ]

21.  Secondary:   The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product   [ Time Frame: Day 1 of administration of study product until day 16 for all episodes ]

22.  Secondary:   The Distribution of Children for Whom Diaper Dermatitis Was Reported and Associated With Study Product   [ Time Frame: Day 1 of administration of study product until day 16 for all episodes ]


  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
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Alejandro Hoberman
Organization: Children's Hospital of Pittsburgh of UPMC
phone: 412-692-5249
e-mail: hobermana@upmc.edu


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

Responsible Party: Alejandro Hoberman, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01511107     History of Changes
Other Study ID Numbers: 10-0083
AI2009058 ( Other Identifier: NIH NIAID )
First Submitted: January 10, 2012
First Posted: January 18, 2012
Results First Submitted: September 30, 2016
Results First Posted: February 10, 2017
Last Update Posted: February 10, 2017



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