Acute Otitis MediaPhase 2NCT01511107

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

A Phase 2 study testing Amoxicillin-Clavulanate, 10 days and Amoxicillin-Clavulanate, 5 days in people with Acute Otitis Media, run by Alejandro Hoberman at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Who is it for?: Ages 6 to 23 months
Conditions the study is for: Acute Otitis Media
What is being tested?: Amoxicillin-Clavulanate, 10 days and Amoxicillin-Clavulanate, 5 days
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 520 participants
Where: 2 sitesUnited States
Study dates: Jan 2012to Oct 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 23 months
All sexes
No healthy volunteers
Child

Who may be able to join

Aged 6 through 23 months
Have evidence of AOM defined as:
recent (within 48 hours) onset of signs and symptoms as described in the Acute Otitis Media - Severity of Symptoms (AOM-SOS) Scale AND a score of ≥3 at the time of enrollment on the AOM-SOS scale
middle ear effusion evidenced by the presence of at least 2 of the following:
decreased or absent mobility of the tympanic membrane
yellow or white discoloration of the tympanic membrane

Show all 13Show fewer

opacification of the tympanic membrane
AND
acute inflammation evidenced by one of the following:
1+ bulging of the tympanic membrane with either intense erythema or otalgia
2+ or 3+ bulging of the tympanic membrane
Has received at least 2 doses of pneumococcal conjugate vaccine
Parent has provided informed consent

Who cannot join

Toxic appearance [capillary refill >3 seconds, systolic blood pressure <60 mm Hg];
Inpatient hospitalization
Clinical or anatomical characteristics that might obscure response to treatment (tympanostomy tubes in place, cleft palate, or Down syndrome)
Sensorineural hearing loss (unilateral or bilateral)
Serious underlying systemic problems that might obscure response to infection (cystic fibrosis, neoplasm, juvenile diabetes)
Concomitant infection that would preclude evaluation of the response of the child's AOM to study product (pneumonia, periorbital cellulitis)

Show all 14Show fewer

Acute wheezing exacerbation which may require treatment with systemic corticosteroids
Known renal or hepatic dysfunction or insufficiency
History of amoxicillin-clavulanate-associated cholestatic jaundice
Immune dysfunction or receipt of immunosuppressive therapy; chronic gastrointestinal conditions (i.e., malabsorption, inflammatory bowel disease)
Co-medications (systemic corticosteroids, more than one dose of systemic antimicrobial therapy within 96 hours, receipt of any investigational drug or vaccine within 30 days)
Hypersensitivity to penicillin, amoxicillin or amoxicillin-clavulanate, or phenylketonuria or known hypersensitivity to aspartame
Unable to complete study, or no access to phone
Previously enrolled in this study or currently enrolled in another study

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Kentucky Pediatric/Adult Research
Bardstown, Kentucky, 40004
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224

Other trials in United States

About this study

Official title: A Phase 2b, Multicenter, Randomized, Double Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of Short-Course Antimicrobial Therapy for Young Children With Acute Otitis Media (AOM) and Impact on Antimicrobial Resistance

The investigators will study whether, in young children with acute otitis media (AOM), shortening length of antibiotic treatment as a strategy for reducing antimicrobial resistance provides satisfactory clinical outcome. This is a Phase 2b multicenter, randomized, double-blind, placebo-controlled clinical trial in 600 children aged 6 through 23 months comparing the efficacy of consistent reduced-duration antimicrobial treatment (5 days) with that of consistent standard-duration treatment (10 days) for each episode of AOM developing during a single respiratory season (October 1 through May 31).

Read the detailed description

Eligible subjects will be randomized at the enrollment visit and will have a telephone call in the course of therapy, and a subsequent visit at the end of therapy. Thereafter, they will be followed through the end of the respiratory season, and their parents will be encouraged to bring their child when concerned about a potential recurrence of AOM. At each recurrence subjects will receive the treatment regimen (either standard- or reduced-duration) to which they were randomized at study entry (consistent treatment strategy).

The recruitment of eligible children with AOM of varying degrees of severity from various primary care practices in 2 separate geographic regions, i.e. Western Pennsylvania and Kentucky, representing urban, suburban and rural demographics will enhance generalizability of study findings and encourage translation to clinical practice.

Conditions: Acute Otitis Media
Being tested: Amoxicillin-Clavulanate, 10 days, Amoxicillin-Clavulanate, 5 days
Keywords: acute otitis media, ear infection, antimicrobial therapy, antimicrobial resistance
Medical subject headings: Otitis Media, Otitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Amoxicillin-Clavulanate, 10 daysDrug
Also called augmentin, amox-clav
Amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-10
Amoxicillin-Clavulanate, 5 daysDrug
Also called augmentin, amox-clav
Amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-5
Plus
Placebo Days 6-10

Study groups in NCT01511107
Study group	Role	What they receive
Amoxicillin-Clavulanate, 10 days	Active comparator	amoxicillin-clavulanate, 90/6.4 mg/kg/day, 2 divided doses, 10 days Receives: Drug: Amoxicillin-Clavulanate, 10 days
Amoxicillin-Clavulanate, 5 days	Other	amoxicillin-clavulanate, 90/6.4 mg/kg/day, 2 divided doses, 5 days plus placebo, 2 divided doses, 5 days Receives: Drug: Amoxicillin-Clavulanate, 5 days

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Proportion of children initially diagnosed with AOM who experience treatment failure at or before the day 12-14 visit.
TF is defined as substantial persistence or worsening of symptoms specifically attributable to AOM, or of otoscopic signs of AOM, after 72 hours from the time of randomization, such that additional antimicrobial therapy is deemed advisable. If a parent/legal guardian is unwilling to continue the assigned study product regimen, the participant will be categorized as TF. Should a participant be administered another systemic antibiotic while taking study medication or prior to Day 16, the participant will be considered a TF. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the tympanic membrane (TM) or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable.
Measured: From 72 hours after randomization until day 21 of the index episode. The mean day for this visit was 13.2.

Secondary outcomes (21)

The Distribution of AOM Recurrences Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit
Proportion of AOM recurrences resulting in treatment failure at or before the day 12-14 visit.
TF is defined as substantial persistence or worsening of symptoms specifically attributable to AOM, or of otoscopic signs of AOM, after 72 hours from the time of the recurrence, such that additional antimicrobial therapy is deemed advisable. If a parent/legal guardian is unwilling to continue the assigned study product regimen, the participant will be categorized as TF. Should a participant be administered another systemic antibiotic while taking study medication or prior to Day 16, the participant will be considered a TF. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the TM or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable.
Measured: From 72 hours after the AOM recurrence was diagnosed until day 21 of the recurrence. The mean day for this visit was 13.3.
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
AOM pathogens are defined as Streptococcus pneumoniae (S pn) or Haemophilus Influenzae (H flu). In the case of S pn, 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. In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: The day 12-14 visit. The mean day for this visit was 13.3.
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
AOM pathogens are defined as Streptococcus pneumoniae (S pn) or Haemophilus Influenzae (H flu). In the case of S pn, 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. In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: The day 12-14 visit. The mean day for this visit was 13.4.
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
AOM pathogens are defined as Streptococcus pneumoniae (S pn) or Haemophilus Influenzae (H flu). In the case of S pn, 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. In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: The day 12-14 visit. The mean day for this visit was 13.2.
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
AOM pathogens are defined as Streptococcus pneumoniae (S pn) or Haemophilus Influenzae (H flu). In the case of S pn, 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. In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: The day 12-14 visit. The mean day for this visit was 13.9.
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
AOM pathogens are defined as Streptococcus pneumoniae (S pn) or Haemophilus Influenzae (H flu). In the case of S pn, 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. In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: The end-of-treatment visit. The mean day for this visit was 13.6.
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
AOM pathogens are defined as Streptococcus pneumoniae (S pn) or Haemophilus Influenzae (H flu). In the case of S pn, 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. In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: The end-of-treatment visit. The mean day for this visit was 13.4.
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
AOM pathogens are defined as Streptococcus pneumoniae (S pn) or Haemophilus Influenzae (H flu). In the case of S pn, 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. In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: Day 1 of study entry until day 365
The Distribution of 6 Week Follow-up, Non-Illness Visits During the Respiratory Season at Which a Nonsusceptible Pathogen is Recovered
AOM pathogens are defined as Streptococcus pneumoniae (S pn) or Haemophilus Influenzae (H flu). In the case of S pn, 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. In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.
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
In the case of S pn, 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.
Measured: The day 12-14 visit specific to the index episode. The mean day for this visit was 13.4.
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
In the case of S pn, 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.
Measured: The day 12-14 visit following a recurrence. The mean day for this visit was 13.6.
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
In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: The day 12-14 visit specific to the index episode. The mean day for this visit was 13.4.
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
In the case of H flu, susceptible was defined as beta-lactamase-negative and ampicillin E test MIC ≤1 µg/mL; nonsusceptible was defined as either beta-lactamase-positive or beta-lactamase-negative and ampicillin E test MIC >1 µg/mL.
Measured: The day 12-14 visit following a recurrence. The mean day for this visit was 13.6.
The Distribution of Children With AOM Recurrences and Relapses Within 60 Days of Enrollment
An episode of AOM occurring after Day 16 will be considered a recurrence. Subjects seen after day 10 and categorized as clinical success who return for an interim/sick visit before day 17 and are found to have AOM will be categorized as a relapse. For secondary outcome analyses, relapses are combined with recurrences.
Measured: Day 1 of study entry until day 60.
The Distribution of Children With AOM Recurrences and Relapses Within the Entire Respiratory Season
An episode of AOM occurring after Day 16 will be considered a recurrence. Subjects seen after day 10 and categorized as clinical success who return for an interim/sick visit before day 17 and are found to have AOM will be categorized as a relapse. For secondary outcome analyses, relapses are combined with recurrences.
Measured: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.
The Mean Rate, Per Month, of Protocol AOM Recurrences and Relapses Within 60 Days of Enrollment
An episode of AOM occurring after Day 16 will be considered a recurrence. Subjects seen after day 10 and categorized as clinical success who return for an interim/sick visit before day 17 and are found to have AOM will be categorized as a relapse. For secondary outcome analyses, relapses are combined with recurrences.
The rate, expressed as a monthly rate, is calculated by dividing the total number of recurrences and relapses within 60 days of enrollment by the number of months of follow-up within 60 days of enrollment.
Measured: Day 1 of study entry until day 60.
The Mean Rate, Per Month, of Protocol AOM Recurrences and Relapses Within the Entire Respiratory Season
An episode of AOM occurring after Day 16 will be considered a recurrence. Subjects seen after day 10 and categorized as clinical success who return for an interim/sick visit before day 17 and are found to have AOM will be categorized as a relapse. For secondary outcome analyses, relapses are combined with recurrences.
The rate, expressed as a monthly rate, is calculated by dividing the total number of recurrences and relapses by the number of months of follow-up.
Measured: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.
The Mean Number of Days Systemic Antibiotics Were Received During the Entire Respiratory Season
Systemic antibiotics include the study product, Amoxicillin-Clavulanate, dispensed for either 10 or 5 days and various concomitant medications, i.e. Amoxicillin, Amox/Clav, Azithromycin, Cefdinir, Cefpodoxime, Ceftriaxone, Erythromycin, Trimethoprim-Sulfamethoxazole, Omnicef, Augmentin, Azithromycin, Cefazolin, Clarythromycin and Ciprofloxacin.
Measured: Day 1 of study entry until day 244. The respiratory season is October 1 - May 31, inclusive.
The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Scores Days 6 to 14
The AOM-SOS scale measures seven discrete items: tugging of ears, crying, irritability, difficulty sleeping, diminished activity, diminished appetite, and fever. The parent rated each of 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, and recorded the ratings in a diary. Each set of ratings was summed to obtain an AOM-SOS score as a measure of symptom burden. Total scores range from 0 to 14, with higher scores indicating greater severity of symptoms. For instances in which the participant was declared a treatment failure, scores are included up to, but not including the day of the failure. Otherwise, scores day 6 to day 14 are included.
Measured: From day 6 of administration of study product until day 14 for all episodes
The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product
Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product.
Measured: Day 1 of administration of study product until day 16 for all episodes
The Distribution of Children for Whom Diaper Dermatitis Was Reported and Associated With Study Product
Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product.
Measured: Day 1 of administration of study product until day 16 for all episodes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2012Oct 2015

First posted18 Jan 2012 (estimated)
Study startJan 2012
Primary completionSep 2015
Study completionOct 2015

Why it stopped: The primary objective of the study was met.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Acute Otitis MediaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 520 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01511107
Sponsor's protocol ID: 10-0083
Other IDs: AI2009058
Status last verified: Oct 2017
First submitted: 10 Jan 2012
Last updated: 6 Oct 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Bjorn H, Shaikh N, Laine MK, Kurs-Lasky M, Timmins H, Jalava J, Huovinen P, Lindholm L, Ruohola A, Hoberman A, Tahtinen PA. Pathogens in the Nasopharynx Before and After Antibiotic Treatment for Acute Otitis Media. Pediatr Infect Dis J. 2026 Aug 10. doi: 10.1097/INF.0000000000005346. Online ahead of print.
PubMed 42572144
Shaikh N, Hoberman A, Paradise JL, Rockette HE, Kurs-Lasky M, Martin JM. Association Between Nasopharyngeal Colonization and Clinical Outcome in Children With Acute Otitis Media. Pediatr Infect Dis J. 2023 Aug 1;42(8):e274-e277. doi: 10.1097/INF.0000000000003956. Epub 2023 Apr 26.
PubMed 37171965
Hoberman A, Paradise JL, Rockette HE, Kearney DH, Bhatnagar S, Shope TR, Martin JM, Kurs-Lasky M, Copelli SJ, Colborn DK, Block SL, Labella JJ, Lynch TG, Cohen NL, Haralam M, Pope MA, Nagg JP, Green MD, Shaikh N. Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children. N Engl J Med. 2016 Dec 22;375(25):2446-2456. doi: 10.1056/NEJMoa1606043.
PubMed 28002709
Martin JM, Hoberman A, Paradise JL, Barbadora KA, Shaikh N, Bhatnagar S, Shope T, Block SL, Haralam MA, Kurs-Lasky M, Colborn DK, Green M. Emergence of Streptococcus pneumoniae serogroups 15 and 35 in nasopharyngeal cultures from young children with acute otitis media. Pediatr Infect Dis J. 2014 Nov;33(11):e286-90. doi: 10.1097/INF.0000000000000445.
PubMed 24911895

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
In-Office Clinical Study of the Solo+ TTD
Ear Infection, Otitis Media
Recruiting
CLIKX® Tympanostomy Tube Delivery System for the Placement of Tympanostomy Tubes
Otitis Media, Otitis Media Chronic
Not yet recruiting
Short-term Application of Lactoferrin Ventilation Tubes
Otitis Media With Effusion (OME)
Recruiting
Nasopharyngeal Carriage of S. Pneumoniae
Nasopharyngeal Carriage, Children, Only
Recruiting
Platelet-Rich Fibrin in Revision Cartilage Tympanoplasty
Tympanic Membrane Perforation, Chronic Otitis Media

All Acute Otitis Media trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2b, Multicenter, Randomized, Double Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of Short-Course Antimicrobial Therapy for Young Children With Acute Otitis Media (AOM) and Impact on Antimicrobial Resistance
ClinicalTrials.gov ID: NCT01511107
Acronym / sponsor ID: 10-0083
Conditions: Acute Otitis Media
Keywords: acute otitis media, ear infection, antimicrobial therapy, antimicrobial resistance
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The primary objective of the study was met.
Enrolment: 520 participants (actual)
Lead sponsor: Alejandro HobermanUniversity, hospital or other
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Study start: Jan 2012
Primary completion: Sep 2015 (actual)
Study completion: Oct 2015 (actual)
First posted: 18 Jan 2012 (estimated)
Results: Posted 10 Feb 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Amoxicillin-Clavulanate, 10 days	Active comparator	Drug: Amoxicillin-Clavulanate, 10 daysamoxicillin-clavulanate, 90/6.4 mg/kg/day, 2 divided doses, 10 days
Amoxicillin-Clavulanate, 5 days	Other	Drug: Amoxicillin-Clavulanate, 5 daysamoxicillin-clavulanate, 90/6.4 mg/kg/day, 2 divided doses, 5 days plus placebo, 2 divided doses, 5 days

Who may qualify

Ages: 6 to 23 months
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (13 listed)

Aged 6 through 23 months
Have evidence of AOM defined as:
AND
Has received at least 2 doses of pneumococcal conjugate vaccine
Parent has provided informed consent

Key exclusion criteria (14 listed)

Toxic appearance [capillary refill >3 seconds, systolic blood pressure <60 mm Hg];
Inpatient hospitalization
Clinical or anatomical characteristics that might obscure response to treatment (tympanostomy tubes in place, cleft palate, or Down syndrome)
Sensorineural hearing loss (unilateral or bilateral)
Serious underlying systemic problems that might obscure response to infection (cystic fibrosis, neoplasm, juvenile diabetes)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Amoxicillin-Clavulanate, 10 daysAlso: augmentin, amox-clavAmoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-10	Drug	Amoxicillin-Clavulanate, 10 days
Amoxicillin-Clavulanate, 5 daysAlso: augmentin, amox-clavAmoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-5 Plus Placebo Days 6-10	Drug	Amoxicillin-Clavulanate, 5 days

Primary outcome

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.
Proportion of children initially diagnosed with AOM who experience treatment failure at or before the day 12-14 visit. TF is defined as substantial persistence or worsening of symptoms specifically attributable to AOM, or of otoscopic signs of AOM, after 72 hours from the time of randomization, such that additional antimicrobial therapy is deemed advisable. If a parent/legal guardian is unwilling to continue the assigned study product regimen, the participant will be categorized as TF. Should a participant be administered another systemic antibiotic while taking study medication or prior to Day 16, the participant will be considered a TF. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the tympanic membrane (TM) or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable.

21 secondary outcomes

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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
The Distribution of Children With AOM Recurrences and Relapses Within 60 Days of Enrollment
Time frame: Day 1 of study entry until day 60.
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.
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.
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.
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.
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
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
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

Results and safety

Results posted to the registry on 10 Feb 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Amoxicillin-Clavulanate, 10 Days	260	238
Amoxicillin-Clavulanate, 5 Days	260	219

Primary outcome: 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.. Number. Unit: participants

Measure	Amoxicillin-Clavulanate, 10 Days n = 238	Amoxicillin-Clavulanate, 5 Days n = 229
Treatment failure	39	77
Treatment success	199	152

Amoxicillin-Clavulanate, 10 Days vs Amoxicillin-Clavulanate, 5 Days: Difference between proportions: -.172 (95% CI -.253 to -.091)

Population analysed: The analysis was intent to treat (ITT). The number of participants is equal to the number of children randomized \& eligible who had a clinical assessment at or before the day 12-14 visit.

21 secondary outcomes are reported in the full results.

Adverse events

Time frame: Parents were interviewed at each scheduled study visit (Day 1, Day 12-14, Day 16-30, 6 week), at the Day 4-6 phone call, at interim illness visits through May 31st, and at the final September visit to determine if their child had any adverse events.. Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Amoxicillin-Clavulanate, 10 Days	3 of 257 (1.2%)	240 of 257 (93.4%)	Not reported
Amoxicillin-Clavulanate, 5 Days	5 of 258 (1.9%)	242 of 258 (93.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42572144Bjorn H, Shaikh N, Laine MK, Kurs-Lasky M, Timmins H, Jalava J, Huovinen P, Lindholm L, Ruohola A, Hoberman A, Tahtinen PA. Pathogens in the Nasopharynx Before and After Antibiotic Treatment for Acute Otitis Media. Pediatr Infect Dis J. 2026 Aug 10. doi: 10.1097/INF.0000000000005346. Online ahead of print.
Derived from this study: PubMed 37171965Shaikh N, Hoberman A, Paradise JL, Rockette HE, Kurs-Lasky M, Martin JM. Association Between Nasopharyngeal Colonization and Clinical Outcome in Children With Acute Otitis Media. Pediatr Infect Dis J. 2023 Aug 1;42(8):e274-e277. doi: 10.1097/INF.0000000000003956. Epub 2023 Apr 26.
Derived from this study: PubMed 28002709Hoberman A, Paradise JL, Rockette HE, Kearney DH, Bhatnagar S, Shope TR, Martin JM, Kurs-Lasky M, Copelli SJ, Colborn DK, Block SL, Labella JJ, Lynch TG, Cohen NL, Haralam M, Pope MA, Nagg JP, Green MD, Shaikh N. Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children. N Engl J Med. 2016 Dec 22;375(25):2446-2456. doi: 10.1056/NEJMoa1606043.
Derived from this study: PubMed 24911895Martin JM, Hoberman A, Paradise JL, Barbadora KA, Shaikh N, Bhatnagar S, Shope T, Block SL, Haralam MA, Kurs-Lasky M, Colborn DK, Green M. Emergence of Streptococcus pneumoniae serogroups 15 and 35 in nasopharyngeal cultures from young children with acute otitis media. Pediatr Infect Dis J. 2014 Nov;33(11):e286-90. doi: 10.1097/INF.0000000000000445.
Individual participant dataSharing planned: No

Related trials for Acute Otitis Media

Active, not recruiting
In-Office Clinical Study of the Solo+ TTD
Ear Infection, Otitis Media
Recruiting
CLIKX® Tympanostomy Tube Delivery System for the Placement of Tympanostomy Tubes
Otitis Media, Otitis Media Chronic
Not yet recruiting
Short-term Application of Lactoferrin Ventilation Tubes
Otitis Media With Effusion (OME)
Recruiting
Nasopharyngeal Carriage of S. Pneumoniae
Nasopharyngeal Carriage, Children, Only
Recruiting
Platelet-Rich Fibrin in Revision Cartilage Tympanoplasty
Tympanic Membrane Perforation, Chronic Otitis Media

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alejandro Hoberman, MD principal investigator

University of Pittsburgh

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Amoxicillin-Clavulanate, 10 days and Amoxicillin-Clavulanate, 5 days in people with Acute Otitis Media, run by Alejandro Hoberman at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01511107, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2017.