Single Dose CHG Pharmacokinetic Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Single Dose CHG Pharmacokinetic Study (NCT03331263), a randomized phase 1 study. The primary outcome is Number of Subjects With Plasma Levels of Chlorexidine Following Systemic Exposure After a Single Topical Application of CHG..

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, crossover Phase 1 study with an enrollment of 12. The registry record describes a 3-period, 3-sequence crossover. Each treatment period involved one of three conditions: a single 2% CHG application to the abdomen, a single 2% CHG application to the groin, or a control procedure without topical application. A wash-out of 7 calendar days separated treatments.

A crossover design exposes participants to more than one treatment condition, rather than assigning each participant to only one parallel group. In general, this can make comparisons within participants relevant, because each person may contribute observations under multiple conditions. It also means the number of participants represented in the results can differ across conditions if participants do not complete every period. The registry record specifically notes that dropout led to different participant counts across arms.

The posted primary-outcome counts are based on 12 participants for abdominal application, 10 for groin application, and 11 for control. These are not identical analysis counts. The exact sequence assignments, reasons for dropout, masking details, and analysis populations are not reported in the registry record. The record identifies the study as single-masked but does not say which study roles were masked.

The sponsor was Medline Industries. The study is listed as completed. Its primary completion date was 2017-08-06, and its start date was 2017-07-21. The design description establishes the treatment conditions and crossover structure, but does not establish the statistical approach used to compare repeated observations. The registry record says no statistical analysis was planned for the pharmacokinetic results, and no analysis is posted for those results.

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.

Before assignment: Each of the 12 subjects were scheduled to receive one of each treatment and randomized to what period they would receive each.

Period 1

Period 2

Period 3

Analysis population for the primary outcome, as defined in the registry: There was no statistical analysis planned on the PK results of this study. Results were reported as is. Study was completed as a 3-period, 3-sequence crossover therefore not all arms were analyzed with same amount of participants due to drop out.

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: There were a total number of 12 subjects that started but only 10 subjects completed. Abdomen CHG application was completed on 12 subjects, Groin CHG application was completed on 10 subjects and control treatment was completed on 11 subjects.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Plasma Levels of Chlorexidine Following Systemic Exposure After a Single Topical Application of CHG., measured over Up to 24 hours after product application.

The primary endpoint counts participants with plasma levels of chlorhexidine following systemic exposure after a single topical CHG application. Plasma measurements were intended to describe whether chlorhexidine was present in blood after application to the abdomen or groin, compared with the control procedure. This is a pharmacokinetic outcome: it concerns systemic exposure after topical use rather than a clinical benefit outcome.

The registry record describes blood sampling before and after each treatment. Samples were collected at 10, 2, and 0.5 hours before treatment, and at 1, 2, 3, 4, 5, 6, 8, and 12 hours following treatment. The stated timeframe for the primary outcome is up to 24 hours after product application. The description says samples were analyzed for plasma levels of chlorhexidine, but the registry record does not report an assay threshold, the definition of a qualifying plasma level, or detailed concentration results.

The posted endpoint is a participant count, not a concentration estimate or a time-course summary. The registry record reports 0 participants with plasma levels in each treatment group. A count outcome is straightforward to describe, but it cannot show the magnitude or timing of concentrations when no concentration values or measurement threshold are posted. The endpoint therefore addresses the recorded occurrence of plasma levels as defined by the study, while important details needed to interpret what counted as a level are not reported in the registry record.

7. Results Posted in the Registry

• Abdominal Application of 2% CHG: 0.0% (0/12) versus 0.0% (0/11) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• Groin Application of 2% CHG: 0.0% (0/10) versus 0.0% (0/11) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record states that no statistical analysis was planned on the pharmacokinetic results and that results were reported as is. It lists no analyses for the primary outcome. The posted participant counts and contrasts can be described, but they should not be mistaken for a prespecified model-based analysis. The statistical methods that would have been used for a formal crossover analysis are not reported in the registry record.

What does the participant count represent?

The endpoint is binary at the participant level: a participant either is or is not counted as having plasma levels under the study’s outcome definition. The result is reported as a count, alongside the number of participants represented in each treatment group. The posted counts are zero for abdominal application, zero for groin application, and zero for control. Because the registry record does not specify the assay threshold or the rule for classifying a result as a plasma level, the clinical and laboratory meaning of the binary classification is not fully described.

In general, binary outcomes are often expressed as a proportion or compared as a risk difference. A risk difference is the event proportion in one condition minus the event proportion in another. The posted risk differences are 0.0 for each active application compared with control. Those contrasts are consistent with the fact that all three posted participant counts are zero. In this study, the registry record does not report a statistical analysis plan or a method used to calculate uncertainty around those contrasts.

Why does the crossover structure matter?

In general, measurements from the same participant across treatment periods are related rather than independent. A crossover analysis may account for that relationship and may also consider period or sequence effects, depending on the design and analysis plan. The registry record identifies a 3-period, 3-sequence crossover but does not report the planned statistical model, treatment of period or sequence, or handling of within-participant correlation. It also says dropout resulted in different participant counts among arms. Without further detail, the posted arm-by-arm counts cannot show how incomplete treatment sequences were handled analytically.

What can the confidence limits tell the reader?

A confidence interval is a statistical summary of uncertainty around an estimate under a specified method and its assumptions. In general, its interpretation depends on the estimation procedure, the data structure, and the analysis population. The posted risk-difference limits are 0.0 to 0.0 for both comparisons. Since the record does not describe how these limits were obtained, and the endpoint has zero counts in every group, these posted limits should not be treated as a comprehensive account of uncertainty or as evidence of exact equivalence.

How should planning illustrations be read?

The sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such calculations, when presented, are planning illustrations rather than observed power and are not the trial’s own design justification. No sample-size justification is reported in the registry record. Because the observed primary-outcome contrasts are zero, a planning illustration based on those contrasts should not be interpreted as evidence that the study had adequate power to detect a meaningful difference. Any numerical planning values beyond the stated assumptions are not reported in the registry record.

General statistical practice distinguishes a planned analysis from a calculation made after results are available. Here, the record explicitly says no statistical analysis was planned for the pharmacokinetic results. It does not provide a prespecified hypothesis test, adjustment method, model, or analysis population for those results. This limits the extent to which the posted contrasts can be interpreted as confirmatory statistical evidence.

10. Confidence Intervals and Precision

The primary results are zero participant counts in each treatment condition: 0 of 12 for abdominal application, 0 of 10 for groin application, and 0 of 11 for control. The posted risk differences are 0.0, with confidence limits of 0.0 to 0.0 for both application-versus-control comparisons. These values describe the posted summaries, but they do not make the underlying occurrence rate known with certainty.

In general, a confidence interval communicates the range of values compatible with an estimate under a particular statistical procedure. Its usefulness depends on the method being appropriate for the endpoint and design. The registry record does not specify how the posted confidence limits were calculated, and it states that no statistical analysis was planned for the pharmacokinetic results. The displayed limits therefore do not supply enough information to assess the uncertainty method or its assumptions.

Zero observed events create a boundary case for many standard estimation methods. In general, a zero count does not establish that an event is impossible; the amount of information depends on the number of participants and the data collection and measurement process. Here, the group counts are limited, differ across treatments, and arise from a crossover with dropout. Moreover, the assay threshold and definition of a qualifying plasma level are not reported in the registry record. Those features constrain interpretation of precision.

The identical zero counts mean the observed risk differences are zero, but this is not the same as demonstrating equivalence or excluding differences in the broader population. The registry record does not report an equivalence margin, a noninferiority margin, or a planned inferential procedure. The posted summaries therefore support a descriptive account of the enrolled participants, not a precise claim that the treatment conditions have identical systemic exposure.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome concerning participants with plasma levels of chlorhexidine and one secondary outcome concerning participants with treatment-emergent adverse events. It does not report a multiplicity strategy, such as adjustment of significance thresholds across outcomes or comparisons. Since no statistical analysis was planned for the pharmacokinetic results and no analyses are listed, there is no reported testing framework from which to assess multiplicity for the primary outcome.

Missing data are especially relevant in a crossover study because participants may not complete every treatment period. The record states that the study was completed as a 3-period, 3-sequence crossover and that dropout resulted in different participant counts across arms. The reported primary-outcome group counts are 12 for abdominal application, 10 for groin application, and 11 for control. The reasons for dropout, timing of withdrawal, missing sample counts, and handling of missing measurements are not reported in the registry record.

The analysis populations are also not described. The registry record does not say whether the counts include all randomized participants, only participants who completed a treatment period, or another defined group. It does not report whether participants were analyzed according to assigned sequence or according to treatment received. The exact relationship between the reported arm counts and the sequence structure is therefore unclear.

These gaps matter because missing period data can affect which participants contribute to each treatment comparison, and repeated observations can require methods that account for the crossover structure. Without a stated analysis population, missing-data approach, or planned statistical model, the posted results are best read as descriptive counts. The record does not support a judgment about the robustness of the comparisons to incomplete data or multiplicity.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists no serious adverse events in the abdominal application group, the groin application group, or the control group. The numbers of participants at risk for serious adverse events are 12, 10, and 11, respectively. No deaths are listed in any group.

For other adverse events, the record lists one affected participant in each group: abdominal application, groin application, and control. The corresponding numbers at risk are 12, 10, and 11. These are counts of affected participants, not counts of all event episodes. The record does not provide the event terms, severity details, timing, or an assessment of whether the events were related to a treatment. No serious adverse event terms are listed.

These figures are descriptive safety reporting. A zero serious-event count means none were recorded in the posted group results; it does not establish that serious events cannot occur. The other adverse-event counts are also too limited to support a comparative safety conclusion on their own, particularly because the group counts differ and the record provides no inferential safety analysis.

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

The posted primary outcome shows zero participants with plasma levels of chlorhexidine in each reported treatment group. The comparison summaries show risk differences of 0.0 for abdominal application versus control and groin application versus control. These are the observed results among the participants represented in the registry record, not estimates that establish identical systemic exposure in the wider population.

The endpoint is a count of participants meeting an outcome definition. The record does not provide the plasma concentration values, assay sensitivity, or threshold for classifying a participant as having a plasma level. Without those details, a zero count cannot be translated into a specific concentration statement. It also does not describe whether levels below a threshold were measured but not counted, or how measurements across sampling times were reduced to the participant-level outcome.

The study’s crossover design and dropout further limit a simple between-group interpretation. The counts differ across conditions, and the registry record does not report the analysis population or method used to account for repeated observations. The record explicitly states that no statistical analysis was planned for the pharmacokinetic results. Thus, the posted risk differences are descriptive and do not provide a formal test of equality or evidence of equivalence.

The safety information is similarly bounded. No serious adverse events or deaths are listed, and one participant in each group is recorded with an other adverse event. The event descriptions and causal assessments are not reported. These counts do not determine whether a treatment caused or prevented an adverse event.

In short, the registry record documents zero participants meeting the posted plasma-level outcome in each condition, but it does not support a broad conclusion about all forms or magnitudes of systemic exposure. It also does not establish comparative efficacy or safety. The study is a small pharmacokinetic investigation with descriptive outcome reporting, and its interpretation depends on measurement and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable because its crossover design and its posted analysis are not the same thing. The record identifies a randomized, single-masked, 3-period, 3-sequence crossover, a structure in which participants may contribute observations under multiple treatment conditions. Yet the registry record says no statistical analysis was planned for the pharmacokinetic results and reports the results as is. That makes clear why design labels alone cannot establish how treatment effects were estimated.

The endpoint also illustrates the limits of a binary count when all reported counts are zero. The result is easy to summarize, but it does not convey concentration values, assay sensitivity, or the pattern across sampling times. Nor does a zero risk difference establish that the treatments are equivalent. Statistical interpretation needs to distinguish the observed sample from the broader uncertainty about the underlying outcome.

Unequal participant counts across treatment conditions are another important feature. The record attributes the differences to dropout, but does not report when or why participants dropped out, how missing periods were handled, or which population was analyzed. In a crossover, these details can affect the interpretation of within-participant comparisons and the relationship between each arm count and the randomized sequences.

The study therefore demonstrates a general statistical lesson: a reported point estimate and confidence limits are not self-interpreting. Readers need to know the outcome definition, analysis plan, missing-data handling, and model assumptions. Those details are not reported for the pharmacokinetic results in this registry record. The posted figures remain useful as descriptive reporting, while the limits of their inferential interpretation should stay explicit.

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 does not report the assay threshold or the operational definition of a qualifying plasma level. It provides participant counts but no plasma concentration values or detailed concentration-time results. As a result, the zero counts cannot indicate the magnitude of any measured values or explain how measurements at different sampling times were summarized into the participant-level endpoint.

The stated primary-outcome timeframe is up to 24 hours after product application, while the described post-treatment collection schedule lists samples through 12 hours. The registry record does not explain this difference. It also describes a total of 12 blood samples per study period while listing collection times before and after treatment; the relationship between that total and the listed schedule is not clarified.

The record identifies a crossover design and says dropout led to different participant counts across arms, but does not report dropout reasons, missing sample details, sequence-specific completion, or missing-data handling. It does not identify the analysis population or describe an analysis that accounts for repeated observations. It states that no statistical analysis was planned for the pharmacokinetic results.

Other limitations include the absence of a reported sample-size justification, a detailed statistical plan, a stated multiplicity approach, and a description of which study roles were masked. The registry record does not provide participant characteristics beyond the enrollment count in the registry record presented for these results. These omissions limit assessment of measurement, precision, and generalizability. The posted data support a descriptive reading of the recorded counts, not a definitive comparative conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Single Dose CHG Pharmacokinetic Study — NCT03331263.
• Registry record last updated 2023-12-15; status last verified 2021-04.
• Results first posted 2023-12-15.
• 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

NCT03331263 is a completed, randomized, single-masked Phase 1 crossover study sponsored by Medline Industries. It enrolled 12 participants and compared single 2% CHG applications to the abdomen and groin with a control procedure without topical application. Treatments were separated by a wash-out of 7 calendar days.

The primary outcome counted participants with plasma levels of chlorhexidine after application. The registry record reports 0 of 12 for abdominal application, 0 of 10 for groin application, and 0 of 11 for control. It states that no statistical analysis was planned for the pharmacokinetic results. No serious adverse events or deaths are listed; one participant in each group is listed with an other adverse event. The record does not report detailed concentration data, the assay threshold, or the handling of missing observations.