Efficacy and Safety Study of Miconazole Oil Versus Vehicle on Fungal Infection of the Ear Canal (Otomycosis): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of Miconazole Oil Versus Vehicle on Fungal Infection of the Ear Canal (Otomycosis) (NCT04432376), a randomized phase 2, phase 3 study. The primary outcome is Percentage of Subjects With Therapeutic Cure.

2. Clinical Question

The central statistical question is whether the proportion meeting this combined cure definition differs between the randomized treatment groups among participants who had a positive fungal culture at baseline. This is narrower than asking about every randomized participant: the record specifies MITT as the efficacy population, while ITT includes all enrolled and randomized participants. The open-label portion addresses safety exposure to active treatment, but it is not described as a randomized comparison for the primary efficacy question.

3. Trial Design

This completed study evaluated miconazole 2% oil against vehicle oil for otomycosis. The record lists Phase 2 and Phase 3, randomized allocation, and a crossover model. Its study title describes a randomized, double-blind study followed by an open-label safety evaluation. The masking field lists triple masking. The narrative does not explain the difference between the double-blind description and the triple-masking classification, so the exact set of masked parties is not reported in the registry record.

The randomized portion compared active oil with vehicle oil in participants with active fungal infection. Both treatments were applied as 5 drops into each ear twice daily for 14 consecutive days. The primary endpoint was assessed 21 days from the first day of drug application. After the randomized portion, an open-label portion administered active miconazole oil using the same application schedule. Participants in the open-label portion may or may not have had active infection.

The registry classifies the design as crossover, but the narrative does not describe treatment sequences, periods, or a within-participant comparison. Those details are not reported in the registry record, so the crossover classification alone does not establish how the comparison was implemented. Enrollment was 382. The listed study start was 2020-07-08, primary completion was 2021-11-01, and status is completed.

The efficacy population was MITT, consisting only of participants with a positive baseline mycological culture. The record also defines ITT as all subjects enrolled and randomized. It reports 89 active and 90 placebo participants in ITT, with 67 active and 64 placebo participants in MITT. There is no reported allocation ratio or account of how participants moved between the randomized and open-label portions.

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.

Double-blind Treatment Period

Reasons for not completing this period:

Enrollment B, Open Label Safety Group.

Analysis population for the primary outcome, as defined in the registry: MITT (modified intent-to-treat) population - only patients with positive mycological culture at Baseline. ITT (intent-to-treat) population were all subjects enrolled and randomized. Active group: ITT=89 (100%), MITT=67 (75.3%); Placebo Group: ITT=90 (100%), MITT=64 (71.1%).

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: Intent-to-Treat (ITT) population - subjects enrolled and randomized according to treatment group.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects With Therapeutic Cure, measured over 21 days from first day of drug application.

The primary endpoint is the percentage of participants with therapeutic cure, assessed 21 days from the first day of drug application. The definition combines mycological cure with clinical cure and is specified for the MITT population, which includes participants with a positive fungal culture at baseline.

Mycological cure means that the follow-up mycological culture is negative. Clinical cure requires absence of all listed otomycosis signs and symptoms: pruritus, debris, and aural fullness. It also requires absence of fungal elements on visual inspection. The record describes symptom grades from none to severe and a visual-inspection score indicating whether fungal elements are present. A score of 0 is best for each measure.

Combining culture results with clinical signs and symptoms makes the endpoint broader than either a laboratory result or a symptom assessment alone. It represents success under the trial's specified definition, not an unrestricted measure of all possible changes in ear infection. The MITT restriction focuses the efficacy assessment on participants whose infection was culture-positive at baseline; participants without that finding are not included in the stated efficacy population.

The registry record gives the endpoint definition and timing but does not report the number or percentage of participants achieving therapeutic cure in either randomized arm. It also does not report an effect estimate or uncertainty interval. Consequently, the posted results cannot establish the size or precision of a treatment contrast for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint mean?

The primary outcome is defined as a count or percentage of participants meeting a yes-or-no therapeutic-cure criterion. A binary endpoint classifies each participant according to whether the combined criteria are met. General explanation: when a binary outcome is summarized as a proportion, the numerator is the number meeting the definition and the denominator is the number assessed in the specified population. A comparison between randomized groups can be expressed using a difference in proportions, a ratio, or another prespecified measure. The registry record reports none of these primary efficacy results, so no effect measure can be interpreted for this trial from the posted efficacy data.

The endpoint combines culture and clinical findings. Mycological cure requires a negative culture; clinical cure requires the listed signs and symptoms to be absent and no fungal elements to be seen. A combined endpoint can be useful when the clinical question concerns several dimensions of disease status, but its interpretation is tied to its exact rule. A participant who does not meet every required component will not meet the combined cure definition, even if some individual findings improve. The record does not report the separate primary-endpoint component results.

Why does the analysis population matter?

The registry defines ITT as all enrolled and randomized participants and identifies MITT as participants with a positive fungal culture at baseline. The efficacy analysis was performed only in MITT. This choice focuses the primary assessment on participants with baseline evidence of infection according to the stated culture criterion. It also means that the reported efficacy population is a subset of the randomized groups, as reflected in the ITT and MITT counts. General explanation: randomized comparisons are most directly preserved when participants are analyzed according to randomized assignment; restricting analysis based on a post-randomization feature can change the population to which the estimate applies. Here, baseline culture status is the stated criterion, but the record does not give details on how missing or unverifiable cultures were handled.

What would a treatment contrast and confidence interval convey?

A group-level cure proportion would describe the observed frequency of therapeutic cure in that arm. A contrast would quantify how the observed outcome differs between active treatment and vehicle under a defined scale. General explanation: a confidence interval gives a range of values compatible with the observed data and the statistical model at a stated confidence level. It communicates precision as well as the range of plausible effects; it does not make the underlying estimate certain, and it does not by itself establish clinical importance. The registry record reports no cure proportions, contrasts, or confidence intervals, so those interpretations cannot be made for the primary endpoint.

What can be said about significance testing?

A p-value, when reported, measures how incompatible the observed data are with a specified null model, given the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. No primary efficacy p-value or testing method is reported in the registry record. The record also does not describe whether tests were one-sided or two-sided, the chosen significance threshold, or the model used for the primary comparison.

How should planning illustrations be understood?

The record describes a planning illustration based on the observed effect, using equal allocation, a two-sided significance level of 0.05, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. Such an illustration is a prospective planning calculation, not a report of observed treatment benefit and not observed power. General explanation: planning sample sizes depend on assumptions about the effect to detect, variability or event frequency, significance level, allocation, and analytic method. An illustration using an observed effect should not be mistaken for the trial's original sample-size justification. The sample-size justification and original design assumptions are not reported in the registry record.

The registry record reports no outcome analyses in its analysis listing. It does not specify whether adjustment was made for baseline variables, how repeated or paired observations were handled, or whether a model accounted for the design classification. The crossover model label is present, but the narrative does not describe treatment periods, sequence, or a crossover analysis. Those analytic details are not reported in the registry record. General explanation: when observations are paired or repeated within participants, the analysis may need to account for their dependence; treating dependent observations as independent can misstate uncertainty.

Over-dispersion is a general concern in models for counts or proportions when outcomes vary more than the model expects. General explanation: if over-dispersion is present and ignored, standard errors may be too small and confidence intervals too narrow. The primary endpoint is described as a participant count/percentage, but the registry record does not report an over-dispersion assessment or a model for the primary outcome. No claim about whether it mattered in this study can therefore be made.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint of therapeutic cure and secondary outcomes of mycological cure and clinical cure. It does not report a multiplicity strategy. In general, testing several outcomes can increase the chance of at least one apparently notable result if each is assessed without accounting for the set of tests. A prespecified strategy may define which outcome is primary, how secondary outcomes are interpreted, or whether testing thresholds are adjusted. The registry record does not say whether such a plan was used, so the secondary outcomes cannot be interpreted as confirmatory or exploratory on the basis of the posted record alone.

The record defines ITT and MITT and gives the corresponding arm counts. Efficacy was performed only in MITT, defined by positive fungal culture at baseline. It does not report whether an ITT efficacy analysis was also performed, how participants with missing cultures were classified, or how missing primary-endpoint observations were handled. Missing data methods, reasons for missing observations, and sensitivity analyses are not reported in the registry record. General explanation: missing outcomes can affect an estimate when the probability of being observed is related to treatment or outcome status; the impact depends on the pattern and assumptions used to address missingness.

There is no primary endpoint result, uncertainty interval, or p-value reported. The record also does not report an analysis plan describing the primary comparison, covariate adjustment, or any interim analyses. These omissions limit assessment of whether the outcome reporting follows a prespecified plan and whether conclusions would be sensitive to analytic decisions. They do not establish that such procedures were absent; their details are simply not reported in the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1.1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute kidney injury (1.1%), hypotension (1.1%).

For serious adverse events, the registry reports the number at risk and the number affected in each group. In the active treatment arm, 1 participant was affected among 89 at risk. In the placebo treatment arm, 0 were affected among 90 at risk. In the open-label treatment arm, 0 were affected among 203 at risk. No deaths were reported in any of these groups.

The registry lists acute kidney injury and hypotension among the top serious adverse-event terms, each reported as 1.1%. The record does not provide further context for those percentages, such as the denominator used for each term, in the information in prose. They should therefore be read as the registry's reported percentages, not converted into counts or compared across groups without that context.

Other adverse events affected 41 participants among 89 at risk in the active group, 51 among 90 at risk in the placebo group, and 9 among 203 at risk in the open-label group. These counts are not the same as serious adverse-event counts. General explanation: adverse-event summaries describe events recorded during a study and do not, on their own, establish that treatment caused an event. The open-label group also differs in treatment and study context from the randomized comparison, so its counts should not be treated as a randomized contrast. The registry does not provide event-level timing, severity detail beyond the serious classification, or attribution information in the reported safety summary.

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

The record establishes the question the randomized portion was designed to address: whether miconazole 2% oil and vehicle oil differ in therapeutic cure among participants with a positive baseline culture. It also describes the treatment schedule, the endpoint definition, and the analysis population. Those details clarify what the intended comparison means. They do not show the outcome of that comparison.

No primary cure percentages, treatment-effect estimate, confidence interval, or p-value are reported in the registry record. Consequently, the posted results do not quantify whether the randomized groups differed, the direction of any difference, or how precisely an effect was estimated. No conclusion about efficacy can be drawn from the enrollment counts, the treatment schedule, or the safety counts.

The endpoint is a combined measure requiring mycological and clinical criteria. It does not represent every possible outcome relevant to otomycosis, and its interpretation applies to the stated MITT population and assessment time. The registry lists mycological cure and clinical cure as secondary outcomes, but their results are not reported. Without those results, it is not possible to tell whether the components align with the combined endpoint.

The safety summary records serious and other adverse events in the randomized arms and in the open-label arm. These counts provide descriptive information, but do not by themselves establish causation or permit a full comparison of risks. The open-label portion is not a randomized active-versus-vehicle comparison. The record also does not report missing-data methods, detailed outcome analyses, or the statistical plan needed to evaluate robustness.

Thus, the registry record is informative about design and outcome definitions, but incomplete for judging the primary efficacy result. The stated completion status does not fill that reporting gap. Any interpretation of treatment effects would require outcome estimates and their uncertainty, along with sufficient information about the analysis and missing data.

13. Why This Trial Matters Statistically

This trial raises several important statistical issues for clinical researchers. First, the primary outcome combines a laboratory measure with clinical findings. A combined endpoint can capture multiple aspects of disease status, but readers need its rule and component results to understand what is driving the overall classification. The registry defines therapeutic cure and names the component outcomes, but does not report their results.

Second, the efficacy population is restricted to MITT participants with positive baseline fungal cultures, rather than all randomized participants. That restriction is explicit and consequential for interpretation: the intended estimate applies to the stated culture-positive population. The record also reports ITT counts, allowing readers to see that the analysis populations differ, but it does not provide efficacy estimates for either population.

Third, the registry classifies the trial as crossover while the narrative describes randomized treatment arms followed by an open-label portion. The available description does not explain treatment sequences, periods, or analysis methods. This illustrates why design labels need accompanying operational detail: the label alone is not enough to determine how observations should be analyzed or what comparison is estimated.

Finally, the absence of primary outcome estimates, uncertainty intervals, and statistical analysis details limits interpretation despite the completed status. Design information and outcome definitions are useful, but they cannot substitute for comparative results. The safety counts also need to be kept distinct from efficacy findings, and the open-label safety group should not be read as a randomized comparator. These distinctions help prevent sample size, endpoint definitions, and adverse-event counts from being mistaken for evidence about the primary treatment contrast.

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.

A key limitation of the registry record is that it does not report the primary therapeutic-cure results. Arm-level percentages, a treatment contrast, confidence intervals, and a p-value are not reported in the registry record. The listed endpoint definition therefore cannot be paired with an observed efficacy estimate, limiting assessment of both effect direction and precision.

The record reports efficacy analysis in MITT, defined by positive culture at baseline, and gives MITT and ITT group counts. It does not explain how missing baseline cultures, missing follow-up cultures, or other missing endpoint data were handled. It also does not report the number of participants with missing primary outcomes or any sensitivity analyses. The extent to which missing information could affect the result cannot be assessed from the registry record.

The design description is incomplete for understanding the crossover classification. Treatment sequence, period details, and the method used to account for within-participant dependence are not reported in the registry record. The masking information also differs between the study title's double-blind description and the triple-masking field; the identities of masked parties are not specified.

The statistical analysis plan, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record. The record describes a planning illustration based on the observed effect, but that is not the same as the original design justification or observed power. The serious adverse-event term percentages lack further denominator context in the reported summary. These reporting gaps restrict evaluation of analytic choices, safety context, and robustness; they do not show that the unreported procedures or analyses were not performed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of Miconazole Oil Versus Vehicle on Fungal Infection of the Ear Canal (Otomycosis) — NCT04432376.
• Registry record last updated 2024-01-19; status last verified 2024-01.
• Results first posted 2022-11-04.
• 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

NCT04432376 is a completed randomized study of miconazole 2% oil versus vehicle oil for otomycosis, with an open-label active-treatment portion. The record lists Phase 2 and Phase 3, enrollment of 382, and a primary endpoint of therapeutic cure assessed 21 days from the first day of application. Both randomized treatments were applied as 5 drops into each ear twice daily for 14 consecutive days.

The efficacy population was MITT, defined as participants with positive baseline culture. The registry reports 67 active and 64 placebo participants in MITT, and 89 and 90, respectively, in ITT. It does not report the primary cure results or their statistical comparison. Safety counts are reported for the randomized and open-label groups, but the open-label portion is not a randomized comparison. Analysis methods, missing-data handling, and multiplicity procedures are not reported in the registry record.