Effects of Aminocaproic Acid (ACA) on Rosacea-specific Inflammation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Aminocaproic Acid (ACA) on Rosacea-specific Inflammation (NCT01398280), a randomized early/phase 1 study. The primary outcome is Kallikrein 5 (KLK5) Protease Activity.

2. Clinical Question

The study asks a mechanistic question: whether topical ACA is associated with a change in a biochemical marker of rosacea-specific inflammation. Its stated hypothesis is that topical ACA will inhibit activation of antimicrobial peptides. The primary outcome, however, is KLK5 protease activity, measured from facial skin surface samples. The registry record describes KLK5 and LL-37 as biochemical markers relevant to the study rationale, but posts results for KLK5 activity only.

This question is narrower than whether a treatment improves rosacea symptoms or appearance. The posted primary measure is laboratory activity expressed in RFU/uL, not a clinical symptom score. The registry record does not report a clinical outcome as a primary endpoint, and it does not post a secondary outcome measure. The study therefore addresses a biochemical response rather than a broader clinical benefit.

3. Trial Design

NCT01398280 is listed as a completed, early phase 1, randomized, parallel-group study sponsored by the University of California, San Diego. Its official title describes a single-site evaluation. The record lists rosacea as the condition and states an enrollment of 15. The study started in 2011-07, with primary completion in 2012-12.

The two interventions were topical aminocaproic acid (ACA) mixed with Vanicream and vehicle cream. The arm descriptions say that participants applied their assigned cream to facial skin twice daily for up to 12 weeks. They also describe 5-6 visits, 2 telephone visits, and tape-strip sampling at each visit to assess KLK5 activity. These descriptions state that both the investigator and subject would be blinded. In contrast, the record's masking field says NONE. This is an inconsistency in the registry record; the actual masking procedures are not reported in a way that resolves it.

Random allocation and a parallel model are recorded, but details of the allocation procedure, such as sequence generation or concealment, are not reported in the registry record. A protocol, statistical analysis plan, and sample-size justification are not reported in the registry record. The primary endpoint timeframe is listed as up to 12 weeks. The endpoint results are reported for 7.0 in the ACA arm and 4.0 in the vehicle arm. Those outcome counts differ from the enrollment entry, but the reasons for the difference are not reported in the registry record. The safety group counts are also reported separately and should not be assumed to represent the same analysis population as the endpoint summaries.

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

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 Kallikrein 5 (KLK5) Protease Activity, measured over Up to 12 weeks.

The primary endpoint is Kallikrein 5 (KLK5) protease activity, reported as a mean with standard deviation in RFU/uL, over a timeframe of up to 12 weeks. The endpoint description says activity was assessed in adult skin from people with rosacea after treatment with vehicle or aminocaproic acid cream. Tape-strip samples were collected from facial skin, and a synthetic fluorogenic trypsin-like proteinase substrate was used. The described measurement is an increase in fluorescence, recorded with SpectraMax GEMINI EM.

The study rationale identifies KLK5 activity as a biochemical marker relevant to rosacea-specific inflammation and to the proposed effect of ACA on antimicrobial peptide activation. As a general statistical point, a biochemical endpoint can assess a biological process directly without necessarily measuring symptoms or functioning. It can therefore be useful for a mechanistic investigation, while remaining distinct from a clinical outcome. A result on KLK5 activity alone does not establish that people feel or function differently.

The posted endpoint is continuous, so its summary uses a mean and standard deviation. The mean describes the central value of the recorded activity in an arm; the standard deviation describes how dispersed the observations are around that mean. The registry record does not report a confidence interval for either arm or a formal comparative estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

The primary endpoint is continuous, and the registry record identifies the reported parameter as a mean. A mean is the arithmetic center of a set of measurements. Here, the measurements are KLK5 protease activity expressed in RFU/uL. The posted means are 581.1 for ACA and 816.5 for vehicle cream. These values summarize the observed measurements in each arm; they do not describe every participant's result and should not be interpreted as a comparison adjusted for other characteristics.

What does the standard deviation describe?

The standard deviation describes how spread out individual measurements are around their arm's mean. The reported standard deviations are 261.0 for ACA and 422.4 for vehicle cream. A larger standard deviation indicates greater spread on the measurement scale, but it does not reveal the exact distribution of results. It is also not a confidence interval and does not directly quantify uncertainty in the estimated mean. As a general statistical point, the standard deviation describes variation among observations, whereas a standard error or confidence interval addresses uncertainty about an estimate.

Why is there no formal comparison to interpret?

The registry record states that values were missing or not estimable for a two-arm comparison of this continuous endpoint. It posts arm-level means and standard deviations but no formal comparative estimate, confidence interval, or p-value. A between-arm analysis would ordinarily quantify how far apart the group outcomes are and how uncertain that estimate is, using a specified analysis method. Without such a result, the arm summaries can be described but the precision of a treatment contrast cannot be assessed from the registry record.

A confidence interval, as a general statistical concept, is a range of values compatible with the data under a specified method and assumptions. It conveys uncertainty about an estimate; it is not a range containing a fixed proportion of individual observations. No confidence interval for the arm contrast is reported in the registry record. A p-value, also not reported for the comparison, would address how unusual data at least as incompatible with a specified null model would be if that model held. It would not measure the size or clinical importance of an effect.

What does randomization contribute?

The allocation is recorded as randomized, with a parallel model. In general, random allocation is intended to reduce systematic differences between groups at assignment. It does not ensure that groups will be alike on every characteristic, especially when the observed endpoint counts are small. The registry record does not report the sequence-generation method, allocation concealment, baseline characteristics, or a detailed analysis plan. Thus, the presence of randomization is important context, but it cannot replace information about implementation and analysis.

How should the sample-size illustration be read?

The planning assumptions associated with the sample-size material specify a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration is based on the observed effect, with the effect to detect expressed as a stated fraction of that observed effect. Any participant counts calculated under those assumptions are planning illustrations, not results from the trial and not observed power. They should not be interpreted as evidence that the study had a particular probability of detecting an effect after the fact. The registry record does not report the trial's own sample-size justification or design calculation.

As a general concept, a planning calculation asks how many participants might be needed for a future study to detect a target effect under chosen assumptions. The answer depends on the assumed effect size, variability, significance level, allocation, and statistical method. A calculation based on an observed effect is especially dependent on that estimate, which can be unstable in a small study. The planning assumptions therefore do not resolve the absence of an estimable comparative result in the posted trial outcomes.

Why can variation complicate analysis?

For continuous outcomes, a standard comparison often relies on assumptions about the outcome distribution and the behavior of variability. As a general point, over-dispersion means that observed variability is larger than a model allows for; ignoring it can make uncertainty appear too small. The registry record does not report an over-dispersion assessment or a model-based comparison, so no such issue can be diagnosed from the posted summaries. The reported standard deviations describe observed spread but do not establish which statistical model would be appropriate.

The small endpoint counts also mean that any estimate could be sensitive to individual observations. The registry record does not provide individual-level measurements, distribution plots, or an analysis describing influential observations. No recalculated comparative result is posted, and there is no sponsor-versus-recalculation discrepancy to resolve. The appropriate reading is therefore descriptive: retain the posted means and standard deviations as summaries, and avoid inferring precision or significance that the registry record does not report.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Aminocaproic Acid (ACA)", "Vehicle Cream")
n   <- c(7, 4)
m   <- c(581.1, 816.5)
sp  <- c(261, 422.4)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Aminocaproic Acid (ACA)  7  581.100  261.000  339.715  822.485
CARM  Vehicle Cream  4  816.500  422.400  144.367  1488.633

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and zero secondary outcomes posted. It also reports zero analyses. This does not establish that no analyses were conducted or that no outcomes were measured; it describes what the record posts. A multiplicity adjustment or a prespecified strategy for multiple endpoints is not reported in the registry record. With only the posted primary outcome measure, the record does not allow a broader evaluation of how multiple statistical tests may have been handled.

The endpoint summaries include 7.0 in the ACA arm and 4.0 in the vehicle arm, while enrollment is listed as 15. The reasons why the endpoint counts differ from the enrollment entry are not reported in the registry record. The record does not provide a participant flow account, reasons for missing outcome values, or information on whether missingness was related to treatment or outcome. It is therefore not possible to determine from the posted information whether the outcome summaries include all participants assigned to each arm or how missing values were handled.

The analysis population is not reported in the registry record. No intention-to-treat, per-protocol, or other population definition is given, and no imputation method is described. The endpoint result should be read as an arm-level summary for the reported endpoint counts, without assuming a particular analysis population or missing-data procedure. The separate adverse-event counts should not be used to fill in the missing details about endpoint analysis populations.

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.

The registry record reports zero serious adverse events and zero deaths in the ACA safety group, for which 11 were listed as at risk. It reports zero serious adverse events and zero deaths in the vehicle safety group, for which 4 were listed as at risk. The record also reports zero other adverse events in both groups, with 11 and 4 listed as at risk, respectively. No top serious adverse event terms are listed.

These are counts in the posted safety groups. They do not show that the risk of an adverse event is absent. A zero count means that no events of that category were recorded in the group represented by the registry entry; it does not rule out events that are uncommon, occur later, or were not captured in the record. The registry record does not provide additional detail about event collection or follow-up beyond the study description.

The safety group counts differ from the endpoint counts, and the registry record does not explain the relationship between these populations. Safety summaries should therefore be kept separate from the KLK5 endpoint results. The absence of reported events in these groups is not a comparative safety analysis and does not establish that either intervention is safer.

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

The posted result describes KLK5 protease activity in participants represented by the endpoint summaries. The ACA arm has a mean of 581.1 RFU/uL and a standard deviation of 261.0; the vehicle arm has a mean of 816.5 RFU/uL and a standard deviation of 422.4. These descriptive values show the observed arm-level summaries, with a lower mean in the ACA group. The registry record does not provide a formal estimate of the between-arm difference or its uncertainty.

That distinction is important. A difference between observed means is not, by itself, evidence that an intervention caused the difference. Randomization can support causal interpretation when the study is appropriately conducted and analyzed, but the registry record does not report an estimable comparison, allocation details, or an analysis population. The inconsistent masking information also leaves uncertainty about how masking was implemented.

The endpoint is biochemical, not a direct measure of symptoms or clinical improvement. The study rationale concerns antimicrobial peptide activation and rosacea-specific inflammation, but the posted primary measure is KLK5 activity. The result does not show whether symptoms changed, whether LL-37 changed, or whether any biochemical pattern persisted beyond the stated timeframe. Those outcomes are not reported in the registry record.

The posted safety counts likewise have a limited interpretation. No serious adverse events or deaths are recorded in the reported safety groups, but this does not establish the absence of risk or a difference in safety between treatments. The endpoint and safety counts are distinct summaries, and the registry record does not explain their population relationship.

In short, the record offers descriptive biochemical and safety summaries from a small early phase study. It does not provide a formal comparative result precise enough to support a claim about the effect of ACA on KLK5 activity, and it does not answer whether ACA changes clinical rosacea outcomes.

14. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between posting arm summaries and reporting a comparative analysis. Means and standard deviations convey the scale and spread of the observed KLK5 measurements. They do not, alone, quantify the treatment contrast or its uncertainty. The record explicitly notes that values were missing or not estimable for a two-arm comparison, so the central inferential question remains unanswered by the posted results.

The reported endpoint counts are small, and the arm summaries show considerable observed spread. In general, small studies can yield imprecise estimates, and individual measurements may strongly influence a mean. That makes clear reporting of comparative estimates, confidence intervals, analysis populations, and missing-data handling especially useful. Those details are not reported in the registry record.

The record also demonstrates why design details must be read together. Random allocation is recorded, but the masking field says NONE while the arm descriptions state that the investigator and subject would be blinded. The record does not resolve this discrepancy. It also does not report the allocation procedures or a statistical analysis plan. Such information helps readers assess how study design and measurement could affect interpretation.

Finally, the primary endpoint is mechanistic rather than clinical. A biochemical measurement may be suitable for an early phase investigation of a biological hypothesis, but it cannot substitute for evidence on symptoms or other clinical outcomes. The posted result is therefore most useful as a description of an early-phase measurement and as an illustration of the limits of drawing inferential conclusions from incomplete comparative reporting.

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 primary limitation is the absence of a reported two-arm comparison for KLK5 activity. Although arm-specific means, standard deviations, and endpoint counts are posted, the registry record does not report a comparative estimate, confidence interval, or p-value. The reasons that values were missing or not estimable for the comparison are not described.

The endpoint counts are 7.0 for ACA and 4.0 for vehicle, while enrollment is listed as 15. The registry record does not report participant flow or explain this difference. It also does not describe the analysis population, missing-data handling, or reasons for unavailable endpoint values. These omissions limit assessment of possible selection or missing-data effects.

Other trial details are also incomplete in the registry record. The allocation method and concealment are not reported, and masking information is inconsistent: the masking field is NONE, whereas the arm descriptions say the investigator and subject would be blinded. Baseline characteristics, a protocol, a statistical analysis plan, and the trial's sample-size justification are not reported in the registry record.

The endpoint is a biochemical measure assessed over up to 12 weeks, rather than a posted clinical outcome. No secondary outcome is posted, so the record does not show whether the biochemical results corresponded to changes in symptoms or other patient-centered outcomes. Safety counts are reported separately from endpoint counts, with no explanation of the relationship between the groups represented in each summary. These limitations restrict interpretation to the descriptive information available for the reported endpoint and safety categories.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of Aminocaproic Acid (ACA) on Rosacea-specific Inflammation — NCT01398280.
• Registry record last updated 2019-09-13; status last verified 2019-08.
• Results first posted 2019-09-13.
• 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

NCT01398280 is a completed, randomized, parallel-group early phase 1 study of topical aminocaproic acid (ACA) mixed with Vanicream versus vehicle cream in people with rosacea. The record lists a single-site evaluation, enrollment of 15, and a treatment period of up to 12 weeks. Its primary endpoint is KLK5 protease activity in RFU/uL, summarized as a mean and standard deviation.

The posted endpoint summaries are 581.1 RFU/uL (standard deviation 261.0; endpoint count 7.0) for ACA and 816.5 RFU/uL (standard deviation 422.4; endpoint count 4.0) for vehicle. The record does not report an estimable two-arm comparison. Serious adverse events, other adverse events, and deaths are recorded as zero in the stated safety groups, but this does not establish absence of risk. Reasons for the endpoint-count differences, analysis population, missing-data handling, and masking inconsistency are not reported in the registry record.