Nitric Oxide Releasing Solution (NORS) Footbath to Treat Athlete's Foot: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nitric Oxide Releasing Solution (NORS) Footbath to Treat Athlete's Foot (NCT02871011), a randomized phase 2 study. The primary outcome is Number of Participants With Complete Cure: Post Treatment (Day 17).

2. Clinical Question

3. Trial Design

The study is registered as a Phase 2 randomized, quadruple-masked, placebo-controlled clinical trial of nitric oxide footbath treatment for tinea pedis. The registry status is completed. Its record also lists a single-group model, despite describing separate control and nitric oxide arms and identifying randomized allocation. This inconsistency in the registry classifications is not explained in the record, so the design is best described using the reported arm details while noting the conflicting model label.

Participants in both arms were assigned a footbath for 30 minutes daily for 3 consecutive days. The control bath contained water; the active bath delivered nitric oxide. The record gives the intent-to-treat enrollment as 20 individuals, but states that only 12 met the per-protocol baseline criteria of a positive fungal culture and positive microscopic evaluation. The primary outcome records complete cure on Day 17, and a secondary outcome is change in Clinical Symptom Severity Score between Day 1 and Day 31.

The record lists six outcome measures and one posted secondary outcome. It reports zero analyses. It does not describe the method used to generate or conceal assignments, the masking roles, or the statistical analysis plan. The registry also does not report a sample-size justification or whether interim analyses were planned. Those omissions prevent a detailed reconstruction of the trial’s planned inferential approach from the registry record alone.

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

Analysis population for the primary outcome, as defined in the registry: Intent to treat enrollment was 20 individuals but per protocol only a total of 12 participants met the criteria for both a positive fungal culture and microscopic evaluation at baseline.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Complete Cure: Post Treatment (Day 17), measured over Day 17.

The primary endpoint is the number of participants meeting the trial’s definition of complete cure at Day 17. The definition combines evidence about fungal status with a clinical symptom threshold: a negative fungal culture or negative microscopic evaluation via KOH preparation, together with a Clinical Symptom Severity Score of at most 8 on the 0–64 scale. The description notes that improvement corresponds to a lower score.

A binary endpoint reduces each participant’s result to whether the stated cure criteria were met or not met at the specified assessment. Reporting a count makes the observed number of participants meeting the criteria visible in each arm. It does not, by itself, describe the uncertainty around an arm-to-arm comparison or establish that an observed difference is statistically distinguishable from chance variation.

Using a combined microbiological and symptom definition can represent more than one aspect of the condition in a single outcome. At the same time, interpretation depends on the precise rule for combining the negative test result and symptom threshold. The registry wording describes the qualifying test result as negative fungal culture or negative microscopic evaluation, alongside the score requirement; further operational detail is not reported in the registry record.

The endpoint is assessed on Day 17, while the listed secondary outcome concerns symptom-score change between Day 1 and Day 31. The two outcomes therefore address different features and assessment times. The primary endpoint’s posted results are counts rather than an adjusted estimate or a confidence interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A binary outcome records whether each participant meets a criterion or does not meet it. For this trial, the criterion is complete cure at Day 17, defined by the stated fungal-test and symptom-score conditions. The posted results are counts of participants meeting the criterion in each arm. Counts are a direct description of observed outcomes, but a count alone does not quantify uncertainty about the frequency of the outcome in a broader population.

What would a two-arm comparison add?

In a two-arm trial, a comparative analysis would estimate how the binary outcome differs between the intervention and control groups. Depending on the chosen statistical method, the result could be expressed as a difference in probabilities, a ratio, or another effect measure, usually with a confidence interval. A confidence interval describes a range of values compatible with the data and the analysis assumptions; its width conveys precision. These are general statistical concepts, not results reported for this trial.

The registry states that values are missing or not estimable for a two-arm comparison of this binary endpoint. Accordingly, the posted record does not support reporting a comparative effect estimate from the sponsor’s analysis. No analysis result is listed in the registry record. The arm counts remain informative as descriptions, but they should not be mistaken for an inferential comparison.

Why do small counts require caution?

When outcome counts are small, estimates based on them can be imprecise and sensitive to the outcome of an individual participant. Some conventional methods rely on approximations that may be poor when counts are sparse. Exact methods or other approaches designed for sparse data may be considered in general, but the method selected for this trial is not reported in the registry record. No specific inferential method should be attributed to the study without that information.

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. For a simple binary outcome, variation is often described using a binomial model; departures from its assumptions can make standard uncertainty estimates misleading. The registry record does not report an over-dispersion assessment, a model specification, or enough analysis detail to determine whether this issue was considered. This is a general methodological consideration, not a finding about the trial.

How should the analysis population be read?

The record reports intent-to-treat enrollment of 20 and says that only 12 met the per-protocol baseline criteria requiring positive fungal culture and positive microscopic evaluation. The primary outcome arm records list 4 control participants and 8 nitric oxide participants. An intent-to-treat analysis generally seeks to retain participants in their assigned groups, while a per-protocol analysis generally focuses on participants who meet specified protocol criteria. These are general definitions. The registry does not describe the complete analysis-population rules used for the posted endpoint counts, so those labels should not be assumed to identify the exact population underlying every result.

What do the planning assumptions mean?

The record describes a planning illustration based on the observed effect, not the trial’s own design. It specifies a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is framed as participants per arm for a target power; time-to-event illustrations use total events. These are planning concepts, not observed outcomes, and such calculations do not establish the power the completed study actually had. The record does not report that these assumptions formed the original trial design or sample-size justification.

More generally, a sample-size calculation asks how much information a future study might need under chosen assumptions about effect, variability, significance level, power, and allocation. If those assumptions change, the resulting planning requirement changes. A calculation based on an observed effect can be especially unstable when the observed data are sparse. The record does not report a trial-specific sample-size justification, so no planning illustration should be read as evidence that this trial was designed with a particular power.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Control", "Nitric Oxide")
n      <- c(4, 8)
events <- c(0, 4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Control  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Nitric Oxide  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and one posted secondary outcome, described as change in Clinical Symptom Severity Score between Day 1 and Day 31. It does not report a statistical analysis plan specifying which outcomes were confirmatory, how outcomes were prioritized, or whether any adjustment for multiple testing was planned. When several outcomes or analyses are examined, the chance of finding at least one apparently notable result can increase; adjustment methods and prespecified hierarchies are general ways researchers may address that issue. The record does not establish which approach, if any, was used in this trial.

The registry reports zero analyses. That means the record does not provide an analysis for the listed secondary outcome or other inferential results to review. It also does not describe how missing outcome observations were handled, whether participants were excluded after randomization, or whether sensitivity analyses were performed. Those details are not reported in the registry record and should not be inferred from the posted counts.

The population note says intent-to-treat enrollment was 20, while only 12 participants met the stated per-protocol baseline criteria. The primary outcome records list arm-specific denominators of 4 and 8. The registry does not fully explain the relationship between these populations or how missing or ineligible observations were treated. Therefore, the posted counts alone cannot establish that every randomized participant was included in an intent-to-treat analysis, nor can they establish the rules for a per-protocol analysis.

These omissions affect interpretation of both precision and generalizability. Missing-data methods can influence estimates when outcome information is unavailable, and analysis-population definitions affect which participants contribute to a result. Without the protocol or a fuller analysis report, the handling of multiplicity, missing observations, and populations is not reported in the registry record.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse-event counts separately for the two groups. In control, 0 serious adverse events are recorded among 7 participants at risk; in the nitric oxide group, 0 are recorded among 13 at risk. The record also lists 0 deaths in each group. These are the posted counts, not estimates of comparative safety, and the denominators are different from those listed for the primary cure outcome.

For other adverse events, the record lists 0 affected among 7 at risk in control and 3 among 13 at risk in the nitric oxide group. No serious-event terms are listed. A count of zero means that no event was recorded in that category for the stated group and risk set; it does not establish that the true risk is zero. With limited information about definitions, ascertainment, and follow-up, the counts alone cannot characterize the full safety profile.

The registry does not explain why the adverse-event risk sets differ from the primary endpoint denominators, nor does it provide event-level descriptions for the other adverse events. The figures should be read strictly as recorded counts, without calculating comparative rates or treating them as a formal safety analysis.

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

The posted result establishes that the registry recorded 0 complete cures among 4 control participants and 4 among 8 nitric oxide participants at Day 17, using the stated combined microbiological and symptom-score definition. It also establishes that the registry did not report an estimable two-arm comparison for this binary outcome. The counts are the direct descriptive result; they are not, by themselves, evidence of a statistically reliable treatment effect.

The information does not establish the precision of a comparative effect, because no comparison estimate or confidence interval is posted. It does not show how the result would change under a different outcome definition, analysis population, or missing-data approach. Nor does it establish that every participant enrolled contributed to the primary endpoint analysis. The registry’s population note distinguishes intent-to-treat enrollment from the participants meeting the per-protocol baseline criteria, but does not provide a full account of the analysis rules.

The result is specific to the Day 17 endpoint and the regimen described: nitric oxide or water delivered as a footbath for 30 minutes daily for 3 consecutive days. The record’s secondary outcome concerns symptom-score change through Day 31, but it does not post an analysis for that outcome. Conclusions about that secondary outcome cannot be drawn from the primary count data.

The safety counts are also limited: serious adverse events and deaths are recorded as zero in both groups, while other adverse events are recorded in the nitric oxide group. These counts use separate risk sets and are not a substitute for a detailed safety analysis. Overall, the record gives a narrow account of observed endpoint and adverse-event counts, but it does not provide the comparative statistical results or supporting analysis detail needed for stronger conclusions.

14. Why This Trial Matters Statistically

This trial illustrates why a randomized design and a posted arm count are not enough, on their own, to understand a clinical result. A binary endpoint is easy to describe as a count, but comparison requires an analysis that quantifies uncertainty. Here, the registry explicitly says that values are missing or not estimable for the two-arm comparison, leaving the reader with descriptive counts but no reported comparative estimate.

The record also highlights the importance of clearly defining the analysis population. It reports intent-to-treat enrollment of 20, but says only 12 met the per-protocol baseline criteria. The outcome records use arm denominators of 4 and 8. Those details make it important to know which participants were eligible, assessed, and included in each analysis. The registry does not provide the complete account needed to resolve those distinctions.

There is also a mismatch between the single-group model label and the record’s randomized control and intervention arms. This does not alter the posted counts, but it limits how confidently the design can be reconstructed from the registry classifications. Clear and consistent registration of design, outcomes, populations, and statistical methods helps readers distinguish planned analyses from results reported after the study.

Finally, the trial record separates a primary cure outcome from a symptom-score secondary outcome and separately lists safety counts. Keeping these questions distinct prevents a descriptive finding on one endpoint from being extended to outcomes that were not analyzed in the record. The statistical lesson is that transparent denominators, analysis rules, and uncertainty estimates are essential complements to the observed counts.

15. 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 registry record leaves several trial-specific questions unresolved. It describes the study as randomized and quadruple masked, but does not report how the randomization sequence was generated, how assignments were concealed, or which participants or investigators were masked. It also labels the model single group while describing control and nitric oxide arms. The record does not explain this classification inconsistency.

The primary endpoint counts are accompanied by a statement that a two-arm comparison is not estimable. No comparative effect estimate, confidence interval, or p-value is reported, and the registry lists zero analyses. The record therefore gives no inferential result for the primary endpoint and no posted analysis of the listed secondary outcome.

The population information is incomplete for interpreting the endpoint denominators. Intent-to-treat enrollment was 20, and the record says only 12 met the stated baseline criteria for the per-protocol population. The endpoint arm records list denominators of 4 and 8, while adverse-event risk sets are 7 and 13. The registry does not explain how these populations relate, how participants were followed, or how missing observations were handled.

Although six outcome measures are listed, only one secondary outcome is posted, and the registry does not report the outcome hierarchy or multiplicity approach. A trial-specific sample-size justification and statistical analysis plan are also not reported in the registry record. These limitations constrain interpretation of the posted counts and prevent reconstruction of the intended and performed analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Nitric Oxide Releasing Solution (NORS) Footbath to Treat Athlete's Foot — NCT02871011.
• Registry record last updated 2019-09-20; status last verified 2019-08.
• Results first posted 2019-09-20.
• 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.

19. Record Summary

The registry record describes a completed Phase 2 randomized, quadruple-masked, placebo-controlled trial of nitric oxide footbath treatment for tinea pedis. The intervention and water control were delivered for 30 minutes daily for 3 consecutive days. Intent-to-treat enrollment was 20; the record says only 12 met the per-protocol baseline criteria of positive fungal culture and positive microscopic evaluation.

The primary endpoint is complete cure at Day 17. The posted counts are 0 of 4 in control and 4 of 8 in the nitric oxide arm. The registry states that a two-arm comparison for this binary outcome is not estimable and lists zero analyses. One secondary outcome is posted: change in Clinical Symptom Severity Score between Day 1 and Day 31.

Serious adverse events and deaths are recorded as zero in both groups; other adverse events are recorded as 0 among 7 at risk in control and 3 among 13 at risk in the nitric oxide group. The registry does not explain the differing analysis and safety denominators or provide a complete statistical analysis plan.