Clinical Study to Compare Two Skin Substitute Categories for Their Effectiveness to Treat Diabetic Foot Ulcers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Study to Compare Two Skin Substitute Categories for Their Effectiveness to Treat Diabetic Foot Ulcers (NCT06557122), a randomized na study. The primary outcome is Percentage of Wound Area Reduction.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group clinical trial with no masking. It is marked completed and reports enrollment of 24 participants. The start date is 2024-07-25, and the primary completion date is 2024-10-25. The study is listed as not applicable for phase. The registry does not report further details about the randomization sequence or allocation concealment.

Participants were assigned to SOC with an advanced bioengineered skin substitute or SOC with an active comparator. The intervention description identifies Helicoll® Advanced Skin Substitute; the brief summary names Epifix® or Grafix® as comparator products. The registry does not say how the active comparator products were allocated or whether all participants in that arm received the same product.

Both groups were to receive SOC. The listed elements include offloading of the ulcer, appropriate sharp or surgical debridement, infection management, and wound care. The brief summary specifies CAM boots or total contact casting in the SOC description, and notes systemic antibiotics only in conjunction with debridement. More detail about SOC is not reported in the registry record.

The primary outcome was mean percentage wound-area reduction over 4 weeks, from Treatment Visit 1 to Treatment Visit 4. The brief summary also describes a 5-week treatment period and lists complete closure, time to complete closure, and the mean number of IP applications among secondary outcomes. The registry reports 12 participants in each arm for the posted primary outcome. Information about participant flow, withdrawals, adherence, analysis populations, and follow-up beyond the stated endpoint timeframes is not reported in the registry record.

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.

Population: Per-Protocol (PP) Population (All Randomized Subjects)

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Wound Area Reduction, measured over 4 weeks.

The primary endpoint is percentage wound-area reduction of the target ulcer. The registry defines it as the average percentage reduction from Treatment Visit 1 to Treatment Visit 4, assessed manually with digital photography, with a stated timeframe of 4 weeks. The endpoint expresses change relative to each target ulcer’s starting area rather than the final area alone. A larger reduction corresponds to a greater observed decrease in area over that assessment interval.

Wound-area reduction is a continuous measure: participants can have values across a range rather than being classified only as having or not having closure. Summarizing this measure with a group mean gives an overall description of the observed change, while the standard deviation describes how much participants’ measurements varied within each group. Those summaries help compare average wound-area changes while retaining more gradation than a binary closure outcome.

Complete closure is a distinct outcome. It records whether an ulcer met a closure criterion by a stated time, rather than the degree of area change along the way. The registry lists closure and time to closure as secondary outcomes. The primary endpoint therefore addresses average area reduction at the specified visits, not whether every ulcer closed or how quickly closure occurred. Details of the closure definition and the measurement procedures beyond the brief description are not reported in the registry record.

7. Results Posted in the Registry

• SOC and Active Comparator: mean 71.30 versus 83.90 on control; difference -12.60 (95% CI -37.75 to 12.55), standardized effect d = -0.40; z-test p = 0.326.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Proportion of Complete Closure

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • SOC and Active Comparator: 25.0% (3/12) versus 50.0% (6/12) on control; risk difference -25.0 percentage points (95% CI -62.4 to 12.4), risk ratio 0.50 (0.16–1.55); unadjusted two-proportion z-test p = 0.206.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SOC and Active Comparator and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address related but distinct aspects of ulcer response. Complete closure is a binary milestone, while time to closure concerns when that milestone occurs. Repeated applications describe treatment use rather than the degree of wound-area reduction. Together, these measures can provide context for the primary continuous endpoint, but they do not measure the same quantity or answer the same question.

The observed closure counts lean in the same direction as the primary point estimate, with more closures in the advanced bioengineered group than in the active-comparator group. That directional pattern is not sufficient to resolve the uncertainty in either outcome. The closure comparison is unadjusted and imprecise, and its confidence interval includes no risk difference. The registry lists time to closure and repeated applications among the secondary outcomes, but detailed analyses for those outcomes are not reported in the registry record.

Secondary results generally carry less evidential weight than a clearly prespecified primary analysis, particularly when several outcomes are examined. Testing multiple outcomes increases the opportunity to observe an apparently notable result by chance unless the analysis plan accounts for multiplicity. The registry record does not report whether such an adjustment or outcome hierarchy was planned. The secondary analyses are also not reported in the registry analysis listing.

Accordingly, the secondary outcomes can be viewed as complementary descriptions, not as independent confirmation of the primary comparison. The pattern across the available information is suggestive in direction for closure, but not conclusive; other secondary measures lack reported analyses. The incomplete reporting makes it difficult to assess the full set of secondary findings or whether all outcomes were handled according to prespecified methods.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With Repeated Applications
• Proportion of Complete Closure
• Time to Achieve Complete Wound Closure

9. Statistical Interpretation

10. Statistical Methods Explained

The posted primary summaries use the mean and standard deviation for a continuous outcome. A mean is the arithmetic average of the participant-level wound-area-reduction values in an arm. The standard deviation describes the variability of those values around the mean. It is not the uncertainty in the mean itself: uncertainty in a group mean depends on both the observed spread and the number of participants contributing data.

What does the mean difference represent?

The primary comparison is a difference between two group means. Its sign depends on the subtraction order. The posted estimate is defined as active comparator minus advanced bioengineered skin substitute, so a negative estimate indicates a lower average in the comparator arm for this sample. The difference is expressed in the same percentage-reduction scale as the endpoint. It is an unadjusted comparison of the posted summaries; adjustment for baseline values or other participant characteristics is not reported in the registry record.

A mean difference focuses on average outcomes and does not require every participant to have a similar result. When observations vary substantially, a group mean can be a less complete description of individual experience. Reporting the standard deviations alongside the means helps show that variability, while the confidence interval for the contrast conveys uncertainty about the average difference.

What does a confidence interval convey?

A confidence interval is a range of values that, under the statistical method’s assumptions, is compatible with the observed data for the contrast. It is not a range containing a fixed proportion of individual participants’ results, nor does it assign a probability to the true value after the data have been observed. An interval that includes zero for a difference does not demonstrate that the groups are identical; it indicates that the observed data do not rule out zero at the corresponding confidence level.

The registry posts a confidence interval and an unadjusted p-value for the primary comparison. A p-value describes how unusual data at least as discrepant as those observed would be under a specified null model. It is not the probability that the null hypothesis is true, and it is not a measure of clinical importance. The registry record does not report a prespecified statistical analysis plan, so the posted p-value should not be assumed to reflect a documented plan for handling multiple outcomes or covariates.

How does the binary comparison differ?

Complete closure is a binary outcome: a participant either meets the closure outcome by the stated time or does not. The posted secondary comparison uses a risk difference, defined as the observed proportion in the active-comparator group minus the observed proportion in the advanced bioengineered group. A risk difference is expressed on the proportion scale. Its confidence interval describes uncertainty in that contrast. It differs from a mean difference because it compares proportions rather than average continuous measurements.

The secondary record also lists relative measures, but they do not substitute for the risk difference or the raw counts. With small groups, a few participant outcomes can have a substantial influence on a proportion and its comparative estimate. The posted interval is therefore important context for reading the point estimate. Registry-reported analyses for the secondary outcomes are absent.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model assumes. When a model understates variability, standard errors may be too small and confidence intervals may be too narrow, making results appear more precise than they are. This is a general statistical consideration, not a finding established by the registry record. The record does not report a model-based over-dispersion assessment for these outcomes. For the posted continuous outcome, the group standard deviations directly indicate observed variability, but the registry does not provide participant-level data to examine its pattern.

For binary outcomes, variability is tied to the event counts and the assumed model. Small samples can make estimates sensitive to individual outcomes and to the method used to form intervals. The registry does not report the detailed analysis method for the secondary comparison, so the exact assumptions behind its interval and p-value are not documented in the registry record.

What is known about the analysis plan?

The registry reports a primary outcome and secondary outcome descriptions, but the registry record does not report the trial’s original sample-size justification, a complete statistical analysis plan, the analysis populations, missing-data procedures, or interim analyses. It also does not report whether analyses were adjusted for baseline characteristics. These omissions limit assessment of whether the displayed comparisons match prespecified procedures. The sample-size illustrations use a stated planning framework and observed effects; they are separate from the trial’s original design assumptions.

11. Confidence Intervals and Precision

The primary mean-difference estimate is -12.6, with a 95% confidence interval from -37.75 to 12.55. The interval is broad and crosses zero. This means the posted data leave substantial uncertainty about the between-arm average difference: values on either side of zero are compatible with the interval. The result does not establish that the groups have the same mean, and the point estimate should not be read as a precise estimate of the population contrast.

The group means are based on 12 participants per arm. Their standard deviations are 24.93 and 36.8, indicating variation among participants within each arm. The small number of observations and this variability are relevant to the width of the estimated contrast’s interval. The registry record does not provide participant-level observations, so the distribution of individual measurements and the influence of particular observations cannot be assessed from the reported summaries.

The unadjusted p-value for the primary comparison is 0.326. It does not measure the probability that there is no difference, nor does it indicate the size or importance of a difference. Read alongside the confidence interval, it reflects that the observed estimate is not sufficiently precise to distinguish clearly among a range of possible contrasts under the unadjusted comparison.

Precision is distinct from whether an outcome is important or how it should be interpreted clinically. The posted summaries describe the trial participants and quantify uncertainty in a group contrast; they do not eliminate uncertainty about how the result would extend beyond this trial. Additional limitations include the absence of a reported analysis plan and incomplete reporting of participant flow and missing-data handling.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning entries and curve illustrate hypothetical sample sizes for detecting effects defined as fractions of the observed effect. For these outcomes, the figures are participants per arm, not total participants or total events. The distinction matters: the numbers describe the size of each comparison group under the planning assumptions, rather than the number enrolled in this completed trial.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The 80% power column means the number of participants per arm in the illustration for a design with an 80% chance of detecting that assumed effect under those assumptions, if the effect and model assumptions were correct. The 90% power column describes the corresponding planning target at 90% power. These are planning illustrations, not the trial’s original design rationale; that rationale is not reported in the registry record.

Each row uses a different fraction of the observed effect. Smaller assumed effects require more participants to detect under the same framework, which is why the illustrated participant counts rise as the assumed effect becomes smaller. The curve represents the planning relationship across those assumptions; it does not show actual recruitment or outcomes from another study.

These illustrations are not observed power. Observed power is not a useful substitute for interpreting the estimate and confidence interval after results are available. The relevant evidence for this trial is the posted outcome estimate and its uncertainty, while the planning entries show how hypothetical designs might be sized under the stated assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -12.600; pooled standard deviation σ = 31.430.
2. n = 2 × (1.96 + 0.842)² × 31.430² / -12.600² = 97.7, rounded up to 98 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -12.6                      # observed difference in means
sigma <- 31.4304382724772                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(6557122)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 98 (80% power), 131 (90% power)
 75% of observed effect: n per arm = 174 (80% power), 233 (90% power)
 50% of observed effect: n per arm = 391 (80% power), 524 (90% power)
power.t.test: 98.6 
Simulated power at n = 98 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary endpoint and lists secondary outcomes, but the registry record does not report a complete statistical analysis plan or how multiple outcomes were to be handled. When several outcomes are analyzed, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures or a prespecified hierarchy can help define how results should be interpreted. No such approach can be assumed for this trial.

The primary comparison is presented as unadjusted. The registry does not report whether any covariates, baseline ulcer characteristics, or other factors were intended for adjustment, or whether a different analysis was prespecified. The registry record also lists no reported analyses for the secondary outcomes. Consequently, the available secondary comparisons cannot be assessed as a complete, prespecified family of tests.

Missing-data handling is not reported in the registry record. The posted primary summaries give 12 participants in each arm, but the record does not explain whether all randomized participants contributed outcome data, how missing visits were handled, or whether any imputation or sensitivity analysis was performed. Equal displayed arm counts alone do not establish that every randomized participant completed every assessment.

The analysis population is also not reported in the registry record. It is therefore unclear whether the posted analyses use all randomized participants, participants who received treatment, or another defined group. Participant flow, exclusions after randomization, and reasons for missing observations are not detailed in the posted information.

Interim analyses and stopping rules are not reported in the registry record. These details cannot be inferred from the completed status or the listed study dates. Taken together, the missing documentation limits reproducibility and makes it harder to judge whether the reported estimates and tests follow the trial’s intended methods. The posted numerical results remain interpretable as summaries and unadjusted comparisons, but claims about prespecification or robustness would go beyond what is reported.

15. 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 lists 12 participants at risk for serious adverse events in each arm and reports zero serious adverse events in each. It also lists 12 participants at risk for other adverse events in each arm and reports zero affected participants in both groups. The death count is zero in each arm. These are the safety counts reported in the registry record for this trial.

Zero reported events in these groups means no events were recorded in the posted categories for the participants counted at risk. It does not establish that an event is impossible or that the interventions have no safety risks. The groups are small, and the registry record does not provide further detail about event definitions, collection methods, severity grading, or observation time for these safety categories.

The absence of listed serious adverse-event terms is consistent with the zero serious-event counts in the posted record. The figures should be interpreted as trial-specific reporting, not as a general safety comparison or a guarantee about outcomes outside the observed participants and study period.

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

The posted results describe a randomized comparison of SOC combined with two skin-substitute categories in participants with Wagner 1 diabetic foot ulcers. For the primary continuous outcome, the observed average percentage wound-area reduction was higher in the advanced bioengineered skin-substitute arm than in the active-comparator arm. The unadjusted mean-difference estimate is uncertain: its confidence interval includes zero and spans values favoring either group.

This result does not establish that the treatments are equivalent. Demonstrating equivalence would require a prespecified equivalence margin and an appropriate design and analysis; those details are not reported in the registry record. Nor does the point estimate alone establish that one approach is superior. It is a sample estimate with uncertainty, based on 12 participants per arm.

The secondary closure counts show a direction consistent with the primary point estimate, but the unadjusted closure comparison is also uncertain. Results for time to closure and repeated applications are not reported in the registry analysis listing. Therefore, the available secondary information cannot fully characterize whether average area reduction corresponded to differences in closure timing or treatment use.

The findings apply directly to the participants and measurements reported for this study. The registry record does not give enough information about participant characteristics, analysis populations, missing data, or treatment implementation to determine how representative the sample was or how the results might generalize. The trial’s original sample-size justification and statistical analysis plan are not reported, limiting evaluation of design choices and prespecification.

These results are statistical descriptions, not medical advice. They do not establish a clinical recommendation, and they should not be taken as proof that either intervention works or does not work. They show the observed group summaries and the uncertainty around the posted comparisons, with important reporting gaps that constrain broader conclusions.

17. Why This Trial Matters Statistically

This trial is statistically instructive because it places a continuous outcome and a binary secondary outcome side by side. Average wound-area reduction preserves information about the amount of change, whereas complete closure reduces the outcome to whether a milestone was reached by a specified time. These endpoints can tell different parts of the clinical story, and one should not be substituted for the other.

The example also illustrates why effect estimates should be read with uncertainty rather than as stand-alone point values. The primary mean difference is negative under the posted subtraction order, but the interval crosses zero and is broad. Reporting the means, standard deviations, contrast, confidence interval, and unadjusted p-value gives readers several complementary ways to understand the observed comparison without treating a single statistic as decisive.

Small groups make transparent reporting especially important. The registry gives 12 participants per arm for the primary outcome, but does not report participant flow, missing-data methods, analysis populations, or the original sample-size rationale. Without those details, readers cannot fully assess who contributed to the analyses or whether the reported methods match a prespecified plan.

The sample-size illustrations offer a separate lesson: planning depends on the effect a future study aims to detect and on explicit assumptions. Smaller target effects require larger groups in the posted illustrations. Those scenarios are not evidence about the trial’s actual power or about whether the observed result is reliable; the estimate and its confidence interval remain central.

Finally, the record shows how secondary endpoints and safety summaries should be interpreted in context. Directional patterns can be informative, but unadjusted secondary analyses and incomplete outcome reporting carry limitations. Clear distinction among observed summaries, uncertainty, planning scenarios, and unreported methods supports more careful statistical interpretation.

18. 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 comparison is based on 12 participants per arm, and the reported standard deviations indicate variability in wound-area reduction. The resulting confidence interval is broad, so the estimated difference is not precise. Participant-level data are not reported, preventing examination of the distribution of changes, influential observations, or whether a small number of participants strongly affected the group means.

The registry describes the design as randomized and unmasked, but does not report details of sequence generation or allocation concealment. Lack of masking can be relevant to outcome assessment, particularly when wound area is measured manually from digital photography. The record does not describe assessor masking, image-reading procedures, or reproducibility checks, so the potential for measurement-related bias cannot be evaluated from the reported information.

The active-comparator description names Epifix® or Grafix®, but the record does not specify which product each participant received or how that choice was made. This limits interpretation of the comparator arm as a single, uniform intervention. The SOC description is also incomplete in the registry record, which restricts assessment of how consistently background care was delivered across groups.

Important reporting details are absent: participant flow, baseline characteristics, analysis populations, missing-data procedures, protocol deviations, and the trial’s original sample-size justification and analysis plan. The secondary outcomes are listed, but their analyses are not reported in the registry analysis listing. These gaps limit assessment of generalizability, prespecification, and robustness. These are reporting limitations; they do not establish that the underlying trial procedures were inadequate.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Clinical Study to Compare Two Skin Substitute Categories for Their Effectiveness to Treat Diabetic Foot Ulcers — NCT06557122.
• Registry record last updated 2025-05-22; status last verified 2025-05.
• Results first posted 2025-05-22.
• 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.

22. Record Summary

The registry record describes completed randomized, parallel-group, unmasked research comparing SOC with an advanced bioengineered skin substitute against SOC with an active comparator for Wagner 1 diabetic foot ulcers. Enrollment was 24, with 12 participants reported in each arm for the primary outcome. The primary endpoint was mean percentage wound-area reduction from Treatment Visit 1 to Treatment Visit 4 at 4 weeks.

The observed means were 83.9 and 71.3, and the posted unadjusted mean difference was -12.6, with a 95% confidence interval from -37.75 to 12.55 and an unadjusted p-value of 0.326. The interval includes zero. Secondary outcomes include complete closure, time to closure, and repeated applications; analyses are not reported for all listed outcomes. The record reports zero serious adverse events and zero deaths in each arm. The trial’s original sample-size justification, detailed analysis plan, analysis populations, and missing-data methods are not reported in the registry record.