Acute Otitis Media (AOM) Therapy Trial in Young Children
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ClinicalTrials.gov Identifier: NCT00377260 |
Recruitment Status :
Completed
First Posted : September 18, 2006
Results First Posted : August 11, 2010
Last Update Posted : December 5, 2016
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Condition or disease | Intervention/treatment | Phase |
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Acute Otitis Media | Drug: amoxicillin-clavulanate Drug: Placebo | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 291 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official Title: | Efficacy of Antimicrobials in Young Children With Acute Otitis Media (AOM) |
Study Start Date : | November 2006 |
Actual Primary Completion Date : | April 2009 |
Actual Study Completion Date : | April 2009 |

Arm | Intervention/treatment |
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Experimental: Amoxicillin-clavulanate
Reconstituted amoxicillin-clavulanate at 90/6.4 mg/kg/day in 2 divided doses for 10 days.
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Drug: amoxicillin-clavulanate
Augmentin ES-600™: Amoxicillin-clavulanate potassium (600/42.9 mg per 5 mL), administered at a dose of 90/6.4 mg/kg/day in 2 divided doses for 10 days with strawberry cream flavor.
Other Names:
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Placebo Comparator: Placebo
Reconstituted placebo in 2 divided doses for 10 days.
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Drug: Placebo
Same base formulation of the licensed product Augmentin ES-600™, with the same strawberry cream flavor. |
- 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 ]Time to resolution of symptoms is defined as the time from randomization until a child's AOM-SOS score reaches 0 or 1. The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 and 3, then once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score. The maximum possible score was 14 and the minimum was 0. A score >=3 was required to be enrolled in the study.
- The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment [ Time Frame: The first 7 days on therapy ]Time to resolution of symptoms is defined as the time from randomization until a child's AOM-SOS score reaches <= 1 on two consecutive occasions. The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) & recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 & 3, & once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score. The maximum possible was 14 and the minimum 0. A score >=3 was required to be enrolled in the study.
- The Weighted Average Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, According to Treatment Assignment [ Time Frame: During the first 7 days of therapy ]The AOM-SOS score is derived from parent scoring each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) associated with AOM as 0, 1 or 2 (none, a little, a lot). The AOM-SOS was administered twice daily the first 3 days of follow-up, then daily for 4 additional days. Symptom burden for each child is determined by calculating the weighted average of symptom scores post-enrollment over the first 7 days of therapy. Scores are weighted by 1/k, where k is the number of post-enrollment assessments taken on that day.
- 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. ]Clinical failure by the on-therapy visit is defined as either failure to achieve substantial improvement in symptoms, or worsening of otoscopic signs, or both.
- The 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. ]Clinical failure by the end of therapy visit is defined as failure to achieve complete or virtually complete resolution of symptoms and of otoscopic signs, but without regard to the persistence of middle ear effusion.
- The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment [ Time Frame: During the first 7 days of therapy ]The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 and 3, then once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score as a measure of symptom burden. The maximum possible score was 14 and the minimum was 0.
- 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 ]The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite & fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1 and twice daily Days 2 and 3. Each set of ratings was summed to obtain an Acute Otitis Media-Severity of Symptoms (AOM-SOS) score. We compared a child's AOM-SOS scores in the first 72 hours to his/her score at enrollment to determine if a child's symptoms got worse (score increased) or remained unchanged or improved (score remained same or decreased).
- The Mean Number of Times Analgesic Medication Was Administered to the Child According to Treatment Assignment [ Time Frame: The first 10 days of follow-up ]The parents were asked to complete a memory aid for the first 10 days of the study. One item asked them to record medications administered to the child in addition to the study medication. The data presented shows the mean number of times analgesic, i.e. ibuprofen or acetaminophen, was administered.
- The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment [ 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. ]Analysis was limited to those adverse events identified as being associated with either the study medication or the antimicrobials administered to children who were treatment failures or as being a complication of acute otitis media.
- The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment [ Time Frame: End-of-therapy visit. The mean day for this visit was 11.6. ]AOM pathogens are defined as Streptococcus Pneumoniae or Haemophilus Influenzae or Moraxella Catarrhalis or Streptococcus Pyogenes. Nasopharyngeal cultures were obtained at the end of therapy visit.
- The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the End-of-therapy Visit According to Treatment Assignment [ Time Frame: End-of-therapy visit. The mean day for this visit was 11.6. ]
- The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment [ Time Frame: Follow-up visit. The mean day for this visit was 22.8. ]AOM pathogens are defined as Streptococcus Pneumoniae or Haemophilus Influenzae or Moraxella Catarrhalis or Streptococcus Pyogenes. Nasopharyngeal cultures were obtained at the follow-up visit.
- The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the Follow-up Visit [ Time Frame: Follow-up visit. The mean day for this visit was 22.8. ]
- The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the On-therapy Visit According to Treatment Assignment [ Time Frame: On-therapy visit. The mean day for this visit was 5.0. ]For tympanograms with values for height, middle-ear air pressure, and gradient width, the probability of Middle Ear Effusion (MEE) was estimated by applying an algorithm developed by Smith et al. If the tympanogram was flat and had no printed values for the 3 fields, the probability of MEE was estimated to be .802 based on the proportion of ears with flat graphs that were found otoscopically, by Smith et al, to have MEE.
- The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the End-of-therapy Visit According to Treatment Assignment [ Time Frame: End-of-therapy visit. The mean day for this visit was 11.6. ]For tympanograms with values for height, middle-ear air pressure, and gradient width, the probability of Middle Ear Effusion (MEE) was estimated by applying an algorithm developed by Smith et al. If the tympanogram was flat and had no printed values for the 3 fields, the probability of MEE was estimated to be .802 based on the proportion of ears with flat graphs that were found otoscopically, by Smith et al, to have MEE.
- The 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. ]For tympanograms with values for height, middle-ear air pressure, and gradient width, the probability of Middle Ear Effusion (MEE) was estimated by applying an algorithm developed by Smith et al. If the tympanogram was flat and had no printed values for the 3 fields, the probability of MEE was estimated to be .802 based on the proportion of ears with flat graphs that were found otoscopically, by Smith et al, to have MEE.
- The 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. ]At each visit parents were asked if they had taken their child to his/her primary care physician since the last contact. Medical records were also reviewed.
- The Mean Number of Emergency Room Visits According to Treatment Assignment [ 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. ]At each visit we asked parents if they had to take their child to the emergency department. We also reviewed medical records to assure even more accurate reporting.
- The Mean Number of Antibiotic Prescriptions, Exclusive of Study Medication, According to Treatment Assignment [ 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. ]This is the number of times, in the course of the study, a child required treatment with an antibiotic other than the blinded study medication.
- The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Having Missed Work According to Treatment Assignment [ 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. ]At each visit, parent or parents were asked if their child's illness had caused either parent to miss a day or partial day of work. The total number of visits is summed across all participants in the respective treatment arms.
- The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Making Special Daycare Arrangements According to Treatment Assignment [ 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. ]At each visit, parent or parents were asked if their child's illness had caused them to make alternative daycare arrangements. The total number of visits is summed across all participants in the respective treatment arms.
- The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the On-therapy Visit According to Treatment Assignment [ Time Frame: On-therapy visit. The mean day for this visit was 5.0. ]Parents were asked to circle the expression that best represented their satisfaction with the study medication. These expressions have an assigned value: Very dissatisfied = 1, Somewhat dissatisfied = 2, Neither satisfied nor dissatisfied = 3, Somewhat satisfied = 4 and Very satisfied = 5.
- The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the End-of-therapy Visit According to Treatment Assignment [ Time Frame: End-of-therapy visit. The mean day for this visit was 11.6. ]Parents were asked to circle the expression that best represented their satisfaction with the study medication. These expressions have an assigned value: Very dissatisfied = 1, Somewhat dissatisfied = 2, Neither satisfied nor dissatisfied = 3, Somewhat satisfied = 4 and Very satisfied = 5.
- The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment [ Time Frame: Follow-up visit. The mean day for this visit was 22.8. ]Parents were asked to circle the expression that best represented their satisfaction with the study medication. These expressions have an assigned value: Very dissatisfied = 1, Somewhat dissatisfied = 2, Neither satisfied nor dissatisfied = 3, Somewhat satisfied = 4 and Very satisfied = 5.

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Ages Eligible for Study: | 6 Months to 23 Months (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- aged 6 to 23 months
- have received at least two doses of pneumococcal conjugate vaccine (Prevnar) and Haemophilus influenzae type B vaccine
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have evidence of acute otitis media (AOM) defined as:
- Recent (within 48 hours), onset of signs and symptoms and a score of greater than or equal to 3 on the AOM-SOS scale.
- Middle ear effusion evidenced by at least two of the following:
- decreased or absent tympanic membrane mobility by pneumatic otoscopy,
- yellow or white discoloration of the tympanic membrane,
- opacification of the tympanic membrane, plus
- 1+ bulging of the tympanic membrane with either marked erythema or otalgia, or
- 2+ or 3+ bulging of the tympanic membrane
Exclusion Criteria:
- certain signs or symptoms (e.g., toxic appearance [capillary refill greater than 3 seconds, systolic blood pressure less than 60 mm Hg], otalgia for a period greater than 48 hours, spontaneous perforation of the tympanic membrane and drainage or temperature greater than or equal to 105 degrees F);
- clinical or anatomical characteristics that might obscure response to treatment (e.g., tympanostomy tube[s] in place or a history of tympanostomy tubes, unrepaired or repaired overt or submucous cleft palate, high-arched palate, or Down's syndrome);
- underlying systemic problems that might obscure response to infection (e.g., serious underlying disease [e.g., cystic fibrosis, neoplasm, juvenile diabetes]), concomitant infection that would preclude evaluation of the response of the child's AOM to study medication, known renal insufficiency (i.e., serum creatinine greater than or equal to 1.5 times upper limit of normal for age), known hepatic insufficiency or a history of amoxicillin-clavulanate-associated cholestatic jaundice or hepatic dysfunction, history of immune dysfunction, deficiency or receipt of immunosuppressive therapy, chronic gastrointestinal conditions (i.e., malabsorption, inflammatory bowel disease), malignancy;
- sensorineural hearing loss either unilateral or bilateral;
- comedications (e.g., systemic corticosteroids at any point while enrolled in the study, more than one dose of systemic antimicrobial therapy within 96, any investigational drug or vaccine;
- hypersensitivity to penicillin, amoxicillin or amoxicillin-clavulanate, or phenylketonuria or known hypersensitivity to aspartame;
- unable to complete the study protocol or not having access to a telephone; and
- current enrollment in another study or previously enrolled in this study.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00377260
United States, Pennsylvania | |
Children's Hospital of Pittsburgh | |
Pittsburgh, Pennsylvania, United States, 15213 |
Principal Investigator: | Alejandro Hoberman, MD | University of Pittsburgh |
Responsible Party: | Alejandro Hoberman, Chief, Division of General Academic Pediatrics, University of Pittsburgh |
ClinicalTrials.gov Identifier: | NCT00377260 |
Other Study ID Numbers: |
05-0142 U01AI066007 ( U.S. NIH Grant/Contract ) |
First Posted: | September 18, 2006 Key Record Dates |
Results First Posted: | August 11, 2010 |
Last Update Posted: | December 5, 2016 |
Last Verified: | October 2016 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
acute otitis media, infants, children |
Otitis Otitis Media Ear Diseases Otorhinolaryngologic Diseases Amoxicillin Clavulanic Acid Clavulanic Acids |
Amoxicillin-Potassium Clavulanate Combination Anti-Bacterial Agents Anti-Infective Agents beta-Lactamase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |