Treatment of Pressure Ulcers Using Biological Skin Substitutes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Pressure Ulcers Using Biological Skin Substitutes (NCT06853210), a randomized na study. The primary outcome is Percent Change in Wound Area.

2. Clinical Question

The comparison concerns two wound-covering approaches used with a padded dressing. The registry describes the collagen-based substitute as applied weekly or as needed, while it describes the amnion/chorion membrane without giving a comparable application schedule. That difference in description matters when interpreting what the treatment contrast represents: the record compares the treatment approaches as described, not an isolated material under a fully specified common schedule.

The posted primary outcome is a continuous measure of change in wound area. The registry also lists complete wound closure, wound size progression, repeated applications, adverse events and treatment satisfaction as secondary outcomes. The stated primary timeframe is 7 weeks. Further details about ulcer characteristics, care setting, participant eligibility and how the population was selected are not reported in the registry record.

3. Trial Design

The registry identifies this study as a randomized, parallel-group trial with no masking. Its status is completed. The listed enrollment is 80. For the posted primary outcome, the registry reports 40 participants in each arm. The listed phase is NA. The sponsor is Adichunchanagiri Institute of Medical Sciences, B G Nagara.

The study began on 2025-03-01, and its primary completion date is listed as 2025-07-10. The registry title describes a comparison of High Purity Type-I Collagen and Amnion/Chorion Membranes for pressure ulcers. Both study arms are described as receiving a biological skin substitute with a padded 3-layer dressing. For the collagen-based substitute, application is described as weekly or as needed; the record does not state an application schedule for the amnion/chorion membrane arm.

Random allocation is intended to create groups that are comparable on average, although chance differences can remain. The parallel design means the groups receive their assigned approaches over the trial rather than crossing over between them, as indicated by the registry’s design classification. No masking means participants and study personnel were not masked to group assignment according to the registry entry. This is relevant because wound measurements and satisfaction assessments can be influenced by knowledge of treatment, depending on how assessments are conducted.

Important design details are not reported in the registry record. These include the method used to generate and conceal the allocation sequence, the eligibility criteria, the setting, the original sample-size justification, and the protocol’s analysis plan. The record does not state whether analysis followed an intention-to-treat approach or describe a per-protocol population. The completion status and posted group results do not, by themselves, resolve these questions.

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 Percent Change in Wound Area, measured over 7 weeks.

The primary endpoint is percent change in wound area, measured from week 1 through week 7 and reported as a mean with a standard deviation. The registry says wound area was measured manually with digital photography. A continuous measure preserves information about the extent of change rather than reducing the result to a yes-or-no classification such as complete closure.

Percent change is used to express the direction and relative amount of change in wound area over the stated observation period. A negative value indicates that the measured area is lower at the end of the change interval than at its reference point, under the usual interpretation of percent change. The registry does not provide the detailed calculation formula, the exact reference measurement used, or image measurement procedures beyond stating that measurement was manual and used digital photography. Those details are important for understanding reproducibility and how measurement variation might affect the endpoint.

The primary measure captures change in wound area, but it is not identical to complete wound closure. A wound can change in area without being completely closed, and a group mean does not describe every participant’s trajectory. The endpoint also does not, on its own, establish how results varied by initial wound characteristics or whether the observed changes persisted after the stated timeframe. These details are not reported in the registry record.

7. Results Posted in the Registry

• Dehydrated Human Amnion/Chorion Membrane: mean -65.10 versus -78.50 on control; difference 13.40 (95% CI 6.99 to 19.81), standardized effect d = 0.92; z-test p = <0.001.

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.

Complete Wound Closure Rates

• 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:
  • Dehydrated Human Amnion/Chorion Membrane: 62.5% (25/40) versus 75.0% (30/40) on control; risk difference -12.5 percentage points (95% CI -32.6 to 7.6), risk ratio 0.83 (0.62–1.12); unadjusted two-proportion z-test p = 0.228.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dehydrated Human Amnion/Chorion Membrane and the control. The interval gives the range of effects that remain compatible with the data.

Mean Number of Repeated Application

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Dehydrated Human Amnion/Chorion Membrane: mean 1.15 versus 0.85 on control; difference 0.30 (95% CI -0.09 to 0.69), standardized effect d = 0.34; z-test p = 0.134.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dehydrated Human Amnion/Chorion Membrane and the control. The interval gives the range of effects that remain compatible with the data.

Patient Treatment Satisfaction

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Dehydrated Human Amnion/Chorion Membrane: mean 3.41 versus 4.33 on control; difference -0.92 (95% CI -1.23 to -0.61), standardized effect d = -1.31; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Dehydrated Human Amnion/Chorion Membrane than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes that broaden the assessment beyond change in area: complete wound closure, wound size progression over time, repeated applications, adverse events and patient treatment satisfaction. These outcomes address different aspects of the treatment experience and should not be treated as interchangeable measures of one underlying effect. Closure is a categorical endpoint, repeated applications concern treatment use, and satisfaction reflects participants’ reported experience.

Across the posted secondary outcomes with numerical comparisons, the pattern is not uniformly aligned in the same way as the primary area-change contrast. The results include both outcomes with evidence of a between-group difference in the unadjusted calculations and outcomes whose intervals include no difference. This is a reason to interpret the secondary findings as a collection of exploratory signals rather than as a single coherent confirmation of the primary result.

The secondary outcomes can help contextualize the primary measure, but they do not change what the primary endpoint measures. A change in mean wound area does not itself imply complete closure, and treatment satisfaction is a distinct outcome rather than a substitute for an objectively measured area change. The registry’s stated timeframes also differ across secondary outcomes, so their results do not necessarily describe the same assessment window.

The registry does not report a multiplicity adjustment or a prespecified hierarchy for secondary analyses. When several outcomes are examined, the chance of at least one apparently notable result arising by chance can increase. Unadjusted p-values therefore carry less weight than a clearly prespecified primary result, especially when the analysis plan and outcome-specific missingness are not described. No sponsor-reported analyses are listed for the posted secondary comparisons.

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

• Complete Wound Closure Rates
• Wound Size Progression Over Time
• Mean Number of Repeated Application
• Adverse Events
• Patient Treatment Satisfaction

9. Statistical Interpretation

10. Statistical Methods Explained

The posted primary comparison is a difference between group means for a continuous outcome. The registry reports a mean percent change and standard deviation for each arm, then gives a mean difference and confidence interval. This is a straightforward way to describe a group contrast when the outcome is numerical. It focuses on the average difference, while the standard deviations describe how widely individual measurements are spread around each group’s mean.

What does the mean difference represent?

The reported difference is oriented as the Dehydrated Human Amnion/Chorion Membrane mean minus the High Purity Type-I Collagen-based Skin Substitute mean. The displayed estimate is 13.4. Because the group means are negative, the positive difference means the amnion/chorion mean is less negative. The difference is expressed in the same percentage-change units as the outcome. It is not a relative risk or a percentage increase in the treatment effect.

A mean is useful for a continuous outcome because it summarizes the group’s average result. It can, however, hide variation in individual responses, skewed distributions or subgroups with different patterns. The registry provides standard deviations but does not provide the participant-level data, distribution plots, or a description of whether the assumptions used for the mean comparison were checked. The record also does not report an adjusted analysis accounting for baseline wound size or other characteristics.

How should the p-value be read?

The unadjusted p-value for the primary summary-statistic comparison is <0.001. In general, a p-value describes how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The record does not report a sponsor-conducted analysis or a full statistical analysis plan, so the p-value should be understood as attached to the posted unadjusted comparison rather than assumed to represent a particular prespecified model.

The confidence interval gives a range of values compatible with the data under the method’s assumptions. Its width reflects uncertainty in the estimated mean difference. It is not a range containing a fixed proportion of individual participants’ outcomes, and it does not guarantee that the true difference lies within the interval. The interval is useful alongside the point estimate because it shows both direction and precision.

Why does variation matter?

The standard deviation measures spread in the observed outcome within an arm. Greater variation generally makes it harder to estimate a group mean precisely when the number of observations is unchanged. A confidence interval around a mean difference incorporates uncertainty in both group means. The registry reports separate standard deviations for the two arms and a pooled standard deviation for the comparison, but it does not explain the analytical choices or provide diagnostics.

General statistical note: when count outcomes or continuous outcomes have variation beyond what a model assumes, over-dispersion can make conventional standard errors too small. That can make confidence intervals too narrow and p-values too small. It is a general consideration rather than a reported feature of this trial; the registry does not provide enough distributional information to assess over-dispersion for the posted primary measure.

What does randomization contribute?

Randomization is a design feature that aims to reduce systematic differences between treatment groups at assignment. It does not guarantee that all prognostic characteristics will be balanced, especially in a trial of this size, and it cannot prevent bias introduced after allocation through missing outcomes, measurement procedures or analysis decisions. Masking is listed as none. That does not prove that measurements were biased, but it makes transparent measurement procedures and independent assessment particularly relevant. The registry’s brief description does not report whether wound measurements were independently assessed or whether assessors used a standardized protocol.

The posted comparison uses the group summaries as they appear in the registry. The record does not report whether every randomized participant contributed a primary endpoint, how missing values were handled, or whether any participants were excluded from analysis. Consequently, the group counts in the posted outcome should not be interpreted as a complete account of participant flow or analysis populations.

11. Confidence Intervals and Precision

The 95% confidence interval for the primary mean difference runs from 6.994 to 19.81 percentage points, around the estimate of 13.4. The interval is entirely above zero. Under the assumptions of the unadjusted comparison, the data are compatible with a positive difference in the direction defined as amnion/chorion minus collagen-based substitute.

Precision is not the same as whether a result is statistically distinguishable from zero. A confidence interval conveys the range of effect sizes compatible with the data under a specified method. A narrower interval indicates greater precision than a wider one, but whether the range is practically important depends on context. The registry does not state a threshold for a clinically important difference in wound-area change, so the clinical importance of the interval cannot be determined from the record alone.

The group standard deviations were 18.2 and 9.8. They describe outcome variability, not uncertainty in the treatment contrast. The confidence interval for the difference incorporates sampling uncertainty in the estimated means. It does not describe the range of individual participants’ outcomes, and it does not account for every possible source of bias or uncertainty in study conduct.

The interval is based on a simple, unadjusted comparison of posted summaries. The registry does not report the original analysis method, missing-data handling, baseline adjustment or an analysis population. These omissions limit how fully the interval’s assumptions and robustness can be assessed. In addition, no masking was reported, and the endpoint involved manual measurement with digital photography. The record does not provide sufficient procedural detail to judge measurement reliability.

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 sample-size figures are planning illustrations derived from the observed effect, not the trial’s original design calculation. For the continuous primary endpoint, the entries are participants per arm. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. Each row considers detecting a stated fraction of the observed effect: 100%, 75% or 50%.

The 80% power column gives the planned participants per arm for a design that would have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true effect and the model assumptions held. The 90% power column describes the corresponding planning target for a 90% chance. These are design probabilities, not probabilities that the trial’s conclusion is correct. The estimates are not observed power.

Smaller effects are harder to distinguish from random variation, so the planning illustrations require more participants per arm when the target is a smaller fraction of the observed effect. The rows therefore show how planning needs can change when a future study aims to detect a more modest effect rather than reproducing the full observed estimate.

The registry does not report the trial’s original sample-size justification or the assumptions used when the trial was designed. These illustrative values should not be taken as evidence that the trial was planned for the displayed effect, or that its actual enrollment was selected using this calculation. They are hypothetical planning references based on the observed comparison and specified 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 = 13.400; pooled standard deviation σ = 14.616.
2. n = 2 × (1.96 + 0.842)² × 14.616² / 13.400² = 18.7, rounded up to 19 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 <- 13.4                      # observed difference in means
sigma <- 14.6164291124748                     # 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(6853210)
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 = 19 (80% power), 26 (90% power)
 75% of observed effect: n per arm = 34 (80% power), 45 (90% power)
 50% of observed effect: n per arm = 75 (80% power), 101 (90% power)
power.t.test: 19.7 
Simulated power at n = 19 per arm: 0.786 (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 does not report whether the study’s protocol specified a hierarchy of outcomes, a multiplicity adjustment, or a strategy for controlling false-positive findings across multiple comparisons. The primary endpoint is identified, but the record does not give a statistical analysis plan explaining how primary and secondary hypotheses were to be interpreted. The secondary p-values are unadjusted. Consequently, they should not be read as if each were the sole planned test in the study.

The registry lists 13 outcome measures and 0 analyses in its analysis count, while its posted results include the primary result and several secondary results. The record does not explain the relationship between those entries. It does not report whether all planned measures were assessed, whether any measures were added or omitted, or how outcomes were selected for reporting. These gaps make it difficult to assess selective reporting or to reconstruct the full analysis process.

Missing-data handling is not reported in the registry record. The posted outcome groups list 40 participants in each arm, but this alone does not establish whether all randomized participants had complete outcome data or whether every participant was included in the analysis. The record does not describe losses to follow-up, withdrawals, exclusions, imputation, or sensitivity analyses.

The analysis population is also not reported. It is therefore not possible to establish from the registry whether results were analyzed according to original random assignment, among participants who received treatment, or using another population definition. These distinctions can matter because excluding participants after randomization can weaken the protection that randomization provides. The absence of these details is a limitation of interpretation, not evidence that a particular method was or was not used.

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.

Most frequent non-serious adverse event terms

The registry reports 0 serious adverse events attributed to treatment in the High Purity Type-I Collagen-based Skin Substitute group and 0 in the Dehydrated Human Amnion/Chorion Membrane group. It lists 40 participants at risk in each group. Deaths are listed as 0 in each arm. No serious adverse-event terms are listed.

These counts describe what is recorded in the registry, not proof that serious events could not occur. The record does not provide a detailed definition of treatment-relatedness, event ascertainment procedures, follow-up completeness, or a breakdown of serious events by type. A zero count in the posted results should therefore be interpreted as no serious treatment-attributed events reported for the listed groups, rather than as evidence of no safety risk.

The registry also reports other adverse events affecting 2 participants in the collagen-based arm and 6 in the amnion/chorion arm. These are separate from the serious-event counts. The record does not provide terms or severity details for those other events, so their clinical character cannot be assessed from the posted information.

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

The registry results describe a randomized comparison of two biological skin-substitute approaches used with padded dressings for pressure ulcers. The primary endpoint is mean percent change in wound area over 7 weeks. The posted group means and the unadjusted comparison indicate a difference in the average area-change outcome, with a confidence interval that does not include zero. This is a statement about the posted data and the simple comparison, not a clinical recommendation.

The result does not show that every participant experienced a similar change, nor does it establish that one approach is preferable for every wound or every person. Group averages can conceal variation. The registry does not report detailed eligibility criteria, participant characteristics, baseline wound features, analysis populations or missing-data procedures. Those limitations affect how confidently the findings can be applied beyond the posted comparison.

The outcome is a measured change in wound area, not a direct measure of all aspects of healing or care. Complete closure, treatment satisfaction, repeated applications and adverse events are separate outcomes. Their results provide different kinds of information and should not be collapsed into a single claim about treatment effect. The registry’s secondary comparisons are unadjusted, and no multiplicity plan is reported.

Interpretation also depends on how the endpoint was measured. The record says that area was measured manually with digital photography but does not report detailed measurement procedures or assessor masking. The trial itself is listed as unmasked. These features do not establish that the outcome was biased, but the registry does not provide enough detail to evaluate measurement reliability or possible influence of knowledge of assignment.

The results also do not establish durability beyond the recorded timeframes or the effect of the approaches in populations and settings not described by the registry. The original sample-size assumptions and sponsor analysis plan are not reported. The results should therefore be understood as a limited account of the outcomes posted for this completed trial, rather than a complete basis for broader conclusions.

17. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should separate the endpoint, the estimated group contrast and the uncertainty around that contrast. The primary outcome is continuous, so the mean difference conveys an average change contrast. The confidence interval adds information about precision, while the standard deviations describe variation among measurements within each arm. Those quantities answer different questions and should not be substituted for one another.

The record also illustrates the value of making the direction of a contrast explicit. The reported mean difference compares the amnion/chorion group with the collagen-based group. Since the means are negative, the positive difference does not mean an increase in wound area in the ordinary sense; it describes a less negative mean change in the group listed first in the comparison. Clear orientation helps prevent misreading.

Randomization and no masking have different implications. Randomization aims to balance groups at assignment, whereas masking can reduce the influence of treatment knowledge on care or assessment. Here the registry identifies randomized allocation but no masking. Because the primary outcome involved manual measurement, fuller reporting of measurement procedures would help readers assess how the design features interact.

Finally, the record distinguishes a posted result from an original design plan. Planning illustrations based on the observed effect can help show how assumptions about target effect size influence future sample-size needs, but they are not evidence of the trial’s original justification or its observed power. Missing details about analysis plans, multiplicity and missing outcomes also limit certainty about how the posted comparisons arose. These are important statistical considerations even when a primary confidence interval is relatively precise.

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.

Several trial-specific limitations follow from the registry’s level of detail. Eligibility criteria and participant characteristics are not reported, so the population represented by the results cannot be described beyond the condition of pressure sores. Baseline wound size and other wound characteristics are also not reported. Without those details, it is not possible to assess clinical comparability at baseline or understand whether results may vary by wound features.

The intervention descriptions are not fully parallel. The collagen-based substitute is described as applied weekly or as needed, while the amnion/chorion membrane description does not state a matching schedule. Both descriptions include a padded 3-layer dressing. Since application frequency is part of the treatment approach, the registry does not allow the material effect to be separated from any differences in treatment delivery.

The study is listed as unmasked, and the primary endpoint was measured manually using digital photography. The record does not describe image capture, measurement reproducibility, assessor masking or quality-control procedures. These omissions limit assessment of measurement error and the potential for assessment bias. They do not demonstrate that either occurred.

The registry does not report the sponsor’s original statistical plan, analysis population, missing-data procedures, multiplicity strategy or detailed participant flow. The record also does not provide sponsor-reported analyses for the posted comparisons. These gaps restrict assessment of whether the summary-statistic comparisons reflect the planned analyses and how robust findings are to incomplete data or alternative methods.

Finally, the posted results concern stated short-term timeframes. The registry does not report follow-up beyond those timeframes, nor does it establish durability. The reported outcome summaries do not provide participant-level trajectories or subgroup results. These limitations constrain interpretation and generalizability.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Treatment of Pressure Ulcers Using Biological Skin Substitutes — NCT06853210.
• Registry record last updated 2025-08-29; status last verified 2025-08.
• Results first posted 2025-08-29.
• 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 a completed, randomized, parallel, unmasked comparison of a High Purity Type-I Collagen-based Skin Substitute and a Dehydrated Human Amnion/Chorion Membrane for pressure ulcers. Listed enrollment is 80, with 40 participants in each posted primary-outcome arm. The primary endpoint is mean percent change in wound area from week 1 through week 7, measured manually with digital photography.

The posted primary comparison reports a mean difference of 13.4, with a 95% confidence interval from 6.994 to 19.81 and an unadjusted p-value of <0.001. Secondary outcomes address closure, wound size progression, repeated applications, adverse events and treatment satisfaction. The registry does not report the original sample-size justification, analysis plan, missing-data methods, analysis populations or multiplicity approach. The results are best interpreted as posted group summaries and unadjusted comparisons within those limits.