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

1. Trial at a Glance

This page covers the registry results for Efficacy of Short-Course Antimicrobial Treatment for Children With Acute Otitis Media and Impact on Resistance (NCT01511107), a randomized phase 2 study. The primary outcome is 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.

2. Clinical Question

The trial asks whether a shorter course of antimicrobial treatment for acute otitis media in young children can achieve a satisfactory clinical outcome while addressing concerns about antimicrobial resistance. The planned comparison was consistent treatment for five days versus consistent treatment for ten days during a single respiratory season. The registry record identifies treatment failure by or at the day 12-14 end-of-treatment visit for the index episode as the primary endpoint.

The registry also lists outcomes concerning recurrence and nasopharyngeal cultures, including whether nonsusceptible pathogens are found during follow-up. These outcomes reflect the trial's interest in antimicrobial resistance, but their results are not reported in the registry record. The primary outcome results and a numerical comparison between treatment groups are also not reported. The record therefore establishes the question and planned comparison, but does not allow a conclusion about the observed clinical outcomes or resistance findings.

3. Trial Design

This was a Phase 2b, multicenter, randomized, parallel-group, placebo-controlled trial. The registry lists quadruple masking; the brief summary describes the trial as double blind. Both descriptions indicate that masking was part of the design, but the registry record does not explain how masking was implemented or which trial roles were masked.

The interventions were two durations of the same antimicrobial regimen. The ten-day arm received amoxicillin-clavulanate at 90/6.4 mg/kg/day in two divided doses for ten days. The five-day arm received the same daily dose for five days, followed by placebo for five days. The brief summary describes treatment of each acute otitis media episode arising during one respiratory season, October 1 through May 31. The primary endpoint, however, is specified for the index episode.

The registry lists enrollment of 520, while the brief summary describes a trial in 600 children. These are different enrollment figures in the record; a reason for the difference is not reported. The record marks the trial as terminated. It gives a start date of 2012-01 and a primary completion date of 2015-09, but the reason for termination is not reported in the registry record.

The record identifies treatment failure at or before the day 12-14 visit as the primary endpoint and lists 22 outcome measures and 22 analyses. It does not report the primary endpoint results, group-level estimates, confidence intervals, p-values, or the analysis plan. The planned enrollment and design describe the trial's intended comparison, but do not establish what effect was observed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 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.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: 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.

6. Primary Endpoint

The registry lists the primary outcome as 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, measured over From 72 hours after randomization until day 21 of the index episode. The mean day for this visit was 13.2..

The primary endpoint is the number or proportion of children categorized as treatment failures by or at the day 12-14 end-of-treatment visit for the index acute otitis media episode. The registry describes the endpoint as a proportion of children initially diagnosed with acute otitis media who experience treatment failure. It defines the analysis population as intent to treat: randomized, eligible children with a clinical assessment at or before the day 12-14 visit.

Treatment failure is defined using clinical criteria. It includes substantial persistence or worsening of symptoms attributable to acute otitis media, or otoscopic signs of the condition, after 72 hours from randomization when additional antimicrobial therapy is considered advisable. A participant is also categorized as a failure if a parent or legal guardian is unwilling to continue the assigned regimen, or if another systemic antibiotic is administered while study medication is being taken or before Day 16. The registry's definition of clinical success requires resolution or substantial improvement of symptoms and otoscopic signs for 48 hours, such that additional antibiotic therapy is not considered advisable; middle-ear effusion may persist.

This endpoint captures whether the assigned course is followed by a clinical course that warrants further treatment under the trial's definition. It is relevant to comparing treatment durations because it focuses on clinical status during the treatment and follow-up period. It does not, by itself, measure antimicrobial resistance. The mean day for the end-of-treatment visit is reported as 13.2. The registry record does not report the numbers or proportions categorized as treatment failures in either arm, so the endpoint definition cannot be used to infer the trial's observed outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is a randomized, parallel-group comparison of two treatment durations. Randomization is intended to make treatment assignment independent of participants' characteristics on average, reducing systematic differences between groups. In a parallel-group trial, participants are assigned to one regimen and followed under that assignment. These general design principles explain the role of randomization; the registry record does not report the sequence-generation or allocation-concealment procedures.

What does the primary endpoint measure?

The primary outcome is a binary classification of treatment failure for the index episode by or at the day 12-14 visit. A binary outcome records whether an event or classification occurred, rather than measuring a continuous quantity such as a laboratory value. The registry's definition combines clinical findings and treatment-related criteria. It includes substantial persistence or worsening of acute otitis media symptoms or otoscopic signs after 72 hours when additional antimicrobial therapy is considered advisable. It also includes unwillingness to continue the assigned study product and use of another systemic antibiotic during the specified period.

Because the endpoint is a classification, the natural group comparison would describe the occurrence of treatment failure in each arm and estimate a contrast between arms. That is a general explanation of how binary endpoints are often interpreted, not a statement about the analysis actually used in this trial. The registry reports the outcome parameter as a number and describes a proportion, but does not provide the observed group results or the statistical method used to compare them.

What does a confidence interval tell the reader?

In general, a confidence interval expresses the uncertainty around an estimated effect under the assumptions of the statistical method. A narrower interval indicates greater precision for that estimate; a wider interval indicates less precision. The interval is not a probability statement that the true effect lies within a particular realized interval. Here, no confidence interval for the primary comparison is reported in the registry record, so its precision cannot be assessed from the posted results.

A p-value, in general, describes how compatible the observed data are with a specified null model, given the analysis assumptions. It does not measure the probability that the null hypothesis is true, nor does it by itself describe the size or clinical importance of an effect. No primary-outcome p-value or testing procedure is reported in the registry record.

Why does the analysis population matter?

The registry describes the primary analysis as intent to treat. It further defines the included participants as randomized and eligible children who had a clinical assessment at or before the day 12-14 visit. Intent-to-treat analyses are generally used to preserve the comparison based on assigned treatment, rather than reclassifying participants according to the treatment they ultimately received. The record's specific eligibility and assessment wording should be retained when interpreting this analysis. It does not report how many participants lacked the required assessment, how missing outcome information was handled, or whether other analysis populations were used.

What can be said about the planning assumptions?

The registry lists enrollment of 520 and its brief summary describes a trial in 600 children. It does not report a sample-size justification, the assumptions underlying a power calculation, or a statistical analysis plan. A sample-size illustration based on an observed effect is a planning exercise, not observed power and not evidence that the trial was designed around that effect. The registry record does not provide the primary outcome estimate needed to assess such an illustration from the clinical results.

General power calculations depend on assumptions about the effect to detect, variability or event frequency, the significance level, allocation, and the analysis method. If any of those assumptions differ from the eventual data or method, the calculation may not describe the study's actual ability to detect an effect. No additional assumptions about the design should be inferred from the enrollment figures alone.

How should the resistance outcomes be read?

The listed secondary outcomes concern nasopharyngeal cultures at enrollment, recurrence, and follow-up, including whether a nonsusceptible pathogen is found at the day 12-14 culture or during follow-up. These outcomes describe culture findings rather than the primary clinical treatment-failure classification. Their interpretation would depend on the outcome definitions, the populations with relevant cultures, and the handling of missing specimens. Those analytic details and the corresponding results are not reported in the registry record.

The registry lists 22 outcome measures and 22 analyses. A family of outcomes can raise multiplicity concerns because testing many hypotheses can increase the chance of at least one apparently unusual result. In general, methods such as prespecifying a primary comparison or adjusting for multiple tests can address different aspects of this issue. The registry record does not report whether a multiplicity procedure was planned or used, so no such adjustment should be assumed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures and 22 analyses. This indicates that the record contains multiple outcome and analysis entries, including a primary treatment-failure endpoint and secondary recurrence and nasopharyngeal culture outcomes. When many outcomes or comparisons are examined, the chance of finding at least one result that appears statistically unusual can increase. This is a general statistical concern, not a claim about the trial's findings.

The registry record does not report whether the investigators prespecified a hierarchy of secondary outcomes, adjusted for multiple comparisons, or treated the secondary analyses as exploratory. It also does not report an analysis plan or interim-analysis procedures. Without that information, the intended control of multiplicity cannot be evaluated. The primary endpoint remains the designated primary outcome in the record, but its results are not reported.

The primary analysis population is described as intent to treat and is defined as randomized, eligible children with a clinical assessment at or before the day 12-14 visit. The number included in that analysis is not reported. The registry does not explain how missing assessments or missing outcome classifications were handled, whether any imputation was used, or whether sensitivity analyses were conducted.

Missing culture specimens could also affect interpretation of the resistance outcomes, because those outcomes depend on nasopharyngeal culture information at specified times. The registry record does not report culture completion, missing-specimen handling, or analyses assessing sensitivity to missing data. No conclusion about the extent or impact of missing information can be drawn from the listed outcome definitions alone.

The enrollment figure in the registry is 520, while the brief summary describes 600 children. The reason for this difference is not reported, and neither figure establishes the denominator for the primary analysis. The record's termination status also does not explain whether outcome reporting was affected by missing data or incomplete follow-up.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastroenteritis (0.4%), fever of unknown origin (0.4%), asthma (0.4%), dehydration (0.4%), wound infection (0.4%).

The registry reports serious adverse events for the two treatment groups. For the ten-day amoxicillin-clavulanate group, 3 serious adverse events are listed among 257 participants at risk. For the five-day group, 5 are listed among 258 participants at risk. The record also reports other adverse events affecting 240 participants in the ten-day group and 242 in the five-day group, with the same respective numbers at risk. These are descriptive counts as listed in the registry; they do not, by themselves, establish a comparative safety effect.

The serious-event terms listed are gastroenteritis, fever of unknown origin, asthma, dehydration, wound infection, and seizure, each shown as 0.4%. Those entries do not establish that every term occurred in each group, and the registry record does not provide group-specific counts for these terms. Death counts are not reported in the registry record.

Counts alone do not convey the timing, duration, severity details, relationship to study treatment, or clinical context of each event. The registry record also does not explain whether participants could contribute more than one event to an event count. Therefore, the listed figures should be read as the posted safety summaries, not as a complete account of individual event histories. They do not explain the trial's terminated status; the reason for termination is not reported.

12. What the Result Does, and Does Not, Mean

The record establishes that the trial was designed to compare five days with ten days of amoxicillin-clavulanate for young children with acute otitis media. It identifies a primary clinical endpoint, defines treatment failure, and lists secondary outcomes focused in part on recurrence and antimicrobial resistance. Those details make the research question and intended measurements clear.

The record does not report the primary endpoint results. There is no reported number or proportion of treatment failures by group, no estimated treatment contrast, and no confidence interval or p-value for that comparison. The posted record therefore cannot establish whether the observed treatment-failure outcome favored either regimen, how large a difference may have been, or how precisely an effect was estimated.

The same limitation applies to the resistance outcomes. The registry describes culture-based outcomes involving nonsusceptible pathogens, but does not report their results. The treatment durations alone do not show whether resistance changed, and the rationale of reducing antimicrobial resistance is not evidence that such a change occurred.

The serious adverse-event counts are descriptive and are reported with participants at risk. They can be read as the registry's safety summary, but the information does not support a broader conclusion about comparative safety, event causation, or the reason the study was terminated. The record does not report death counts.

Thus, the meaning of the available information is primarily methodological: it documents a randomized comparison, the treatment regimens, the endpoint definitions, and selected safety counts. It does not supply the clinical or culture results needed to assess the effects of the treatment-duration strategies. The registry marks the trial as terminated, but termination alone is not an outcome and does not reveal why the trial stopped.

13. Why This Trial Matters Statistically

This trial poses a useful statistical question because it places a treatment-duration strategy alongside both clinical outcomes and resistance-related measurements. The primary endpoint is treatment failure for the index episode, while the secondary outcomes include recurrence and nasopharyngeal culture findings. These outcomes represent different dimensions of the research question and should not be treated as interchangeable measures.

The primary endpoint definition also illustrates that clinical outcomes may combine several kinds of information. It includes symptoms, otoscopic signs, decisions about whether further antimicrobial treatment is advisable, willingness to continue the assigned product, and use of another systemic antibiotic. Such a composite classification can be clinically informative, but its interpretation depends on knowing each component and the rules used to assign the outcome. The registry record describes those rules but does not report the resulting group estimates.

The design makes the treatment-duration contrast explicit: both arms use the same daily dose, with placebo in the five-day arm after active treatment ends. This structure defines the intended comparison while maintaining a similar study regimen over ten days. The registry lists quadruple masking, and the brief summary describes the trial as double blind; the record does not give further implementation details.

The entry also highlights why statistical interpretation requires results as well as design information. Randomization and a clearly defined endpoint do not substitute for group counts, effect estimates, and uncertainty intervals. Likewise, a list of resistance outcomes does not establish a resistance effect without the culture results and information about missing specimens.

Finally, the enrollment figures differ between the registry and brief summary, and the study is marked terminated without a recorded reason. These details make careful separation of what was planned, what was recorded, and what can be concluded especially important. The registry record supplies substantial context for the question, but not the outcome evidence needed to resolve it.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpreting this trial from the registry record is the absence of reported primary outcome results. The record defines treatment failure and describes the analysis population, but gives no group-specific outcome counts or proportions, treatment-effect estimate, confidence interval, or p-value. The clinical comparison therefore cannot be quantified or assessed for precision.

Results for the listed secondary outcomes are also not reported. This includes the recurrence and nasopharyngeal culture outcomes relevant to antimicrobial resistance. The record does not report the number of cultures available at each assessment, the handling of missing specimens, or the results among children with particular baseline culture findings.

Enrollment is recorded as 520, while the brief summary describes a trial in 600 children. The reason for the differing figures is not reported, and the number in the primary analysis population is not stated. The registry defines that population as randomized, eligible children with a clinical assessment at or before the day 12-14 visit, but does not give the count meeting those criteria or explain how missing assessments were treated.

The record marks the trial as terminated, without reporting the reason. It also does not report the statistical analysis plan, sample-size justification, allocation procedures, interim analyses, or whether multiplicity adjustments were planned or used. The registry lists quadruple masking, while the brief summary calls the study double blind; further details on masking are not reported.

The safety information is limited to posted event counts and selected terms. The record does not give the context needed to evaluate event timing, treatment relationship, or the reason for termination. These limitations restrict interpretation of both efficacy and safety and should not be filled by assumptions about the trial.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy of Short-Course Antimicrobial Treatment for Children With Acute Otitis Media and Impact on Resistance — NCT01511107.
• Registry record last updated 2017-10-06; status last verified 2017-10.
• Results first posted 2017-02-10.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

This Phase 2b, multicenter, randomized, parallel-group trial compared five days with ten days of amoxicillin-clavulanate for young children with acute otitis media. The five-day regimen was followed by placebo; both groups received the same stated daily dose during active treatment. The brief summary describes children aged 6 through 23 months and treatment during a single respiratory season.

The primary endpoint was treatment failure by or at the day 12-14 visit for the index episode. The registry describes an intent-to-treat analysis among randomized, eligible children with an assessment by that visit. Enrollment is listed as 520, while the brief summary describes 600 children; the reason for the difference is not reported.

The trial is marked terminated. Primary and secondary outcome results, the reason for termination, and details of the analysis plan are not reported in the registry record. Descriptive safety counts are listed for serious and other adverse events.