Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers (NCT02447172), a randomized phase 3 study. The primary outcome is Percent of Patients With a Clinical Outcome of Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection).

2. Clinical Question

The clinical question concerns the added topical treatment within a care plan that included systemic antibiotics and standard ulcer care in all three groups. Thus, the comparison is not gentamicin sponge versus no treatment. It is gentamicin sponge added to the shared care against either a placebo sponge or no sponge.

The placebo comparison addresses the difference between active and placebo sponges under the shared care plan. The no-sponge comparison addresses the active sponge against shared care without a sponge. These contrasts answer related but distinct questions. In particular, the no-sponge group does not control for receiving a sponge, while the placebo group does.

The registry record describes a phase 3 randomized, blinded study. It reports clinical cure as the primary outcome and lists reinfection, time to clinical response, and amputation associated with the target ulcer as secondary outcomes. The posted primary outcome results concern the defined follow-up visit; they do not by themselves describe the full course of recovery or later outcomes.

3. Trial Design

The study was randomized, double-blind, and parallel-group, with three treatment groups. The registry record reports enrollment of 524 and describes allocation in a 2:1:1 ratio. The groups received daily gentamicin sponge, matching placebo sponge, or no sponge. All groups received systemic antibiotic therapy and standard ulcer care, and treatment was planned for up to 28 days.

Participants were expected to attend weekly clinic visits during treatment for safety and efficacy assessments. After treatment, the schedule included follow-up visits approximately 10, 30, 60 and 90 days after treatment stopped. The primary outcome was assessed at follow-up visit 1, approximately 10 days after the end of treatment. The secondary outcome timeframes extend to 90 days after treatment stopped, except that no results for time to clinical response are posted in the record.

The primary outcome results use a modified intent-to-treat population. The registry describes this as randomized participants who received any dose in the gentamicin-sponge or placebo-sponge groups, or who were randomized to the no-sponge group, with an exclusion for specified early termination before follow-up visit 1. Arm sizes for the primary outcome are 257 for gentamicin sponge, 129 for placebo sponge, and 131 for no sponge. Safety-event denominators differ from the primary outcome denominators in the gentamicin group; the record does not explain the difference.

The study status is completed. The registry record does not report the original sample-size justification, the trial’s prespecified statistical analysis plan, or details about how masking was implemented across the three groups. The design description alone does not establish whether the trial had adequate power for each comparison or secondary outcome.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: modified intent to treat consisted of randomized patients who received any dose of gentamicin-sponge or placebo-sponge or who were randomized to the nosponge arm, and who were not early-terminated for one treatment-unrelated reasons before F/U visit 1.

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 of Patients With a Clinical Outcome of Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection), measured over approximately 10 days after end of treatment.

The primary endpoint was the percentage of participants with clinical cure, defined as resolution of all clinical signs and symptoms of infection. It was assessed at follow-up visit 1, approximately 10 days after treatment ended. The primary analysis population was the modified intent-to-treat population described in the registry record.

This endpoint represents a binary outcome at a particular follow-up: each participant either met the clinical-cure definition or did not. Reporting the percentage makes the group-level frequency of cure interpretable, while comparing those percentages describes how often the outcome occurred across treatment assignments. The registry also posts counts of participants meeting the outcome: 177 in the gentamicin-sponge group and 53 in the placebo-sponge group. The corresponding posted percentages are 69% and 41%.

Clinical cure was used as the primary efficacy measure, but the registry record does not report the rationale for selecting it or the criteria used to assess individual signs and symptoms beyond the stated definition. Nor does the result establish how durable a cure was after the primary assessment. Later follow-up was scheduled, and reinfections and amputations were listed as secondary outcomes, but those outcomes address different aspects of the clinical course.

As a general statistical point, a binary endpoint simplifies a complex clinical state into a yes-or-no outcome at a defined time. That makes group percentages straightforward to compare, but it does not convey the severity of remaining symptoms, the timing of improvement, or individual differences in clinical course.

7. Results Posted in the Registry

• Gentamicin Sponge Group: 68.9% (177/257) versus 41.1% (53/129) on control; risk difference 27.8 percentage points (95% CI 17.6 to 38.0), risk ratio 1.68 (1.34–2.09); unadjusted two-proportion z-test p = <0.001.
• No Sponge Group: 35.9% (47/131) versus 41.1% (53/129) on control; risk difference -5.2 percentage points (95% CI -17.0 to 6.6), risk ratio 0.87 (0.64–1.19); unadjusted two-proportion z-test p = 0.388.

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.

Number of Patients With Re-infections

• 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:
  • Gentamicin Sponge Group: 4.3% (11/257) versus 1.6% (2/129) on control; risk difference 2.7 percentage points (95% CI -0.5 to 6.0), risk ratio 2.76 (0.62–12.27); unadjusted two-proportion z-test p = 0.161.
  • No Sponge Group: 3.1% (4/131) versus 1.6% (2/129) on control; risk difference 1.5 percentage points (95% CI -2.1 to 5.1), risk ratio 1.97 (0.37–10.57); unadjusted two-proportion z-test p = 0.420.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Gentamicin Sponge Group and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between No Sponge Group and the control. The interval gives the range of effects that remain compatible with the data.

Percent of Subjects That Had an Amputation Associated With the Target Ulcer

• 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:
  • Gentamicin Sponge Group: 1.2% (3/257) versus 0.0% (0/129) on control; risk difference 1.2 percentage points (95% CI -0.1 to 2.5); unadjusted two-proportion z-test p = 0.218.
  • No Sponge Group: 1.5% (2/131) versus 0.0% (0/129) on control; risk difference 1.5 percentage points (95% CI -0.6 to 3.6); unadjusted two-proportion z-test p = 0.159.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Gentamicin Sponge Group and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between No Sponge Group and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address different parts of the clinical course: reinfection after treatment, time to clinical response, and amputation associated with the target ulcer. The posted count results cover reinfections and amputations through 90 days after treatment stopped. Although time to clinical response appears in the registry’s list of secondary outcomes, its result is not reported in the registry record.

Across the posted secondary results, event counts are small, and the comparisons are less precise than the primary comparison. The confidence intervals for the posted reinfection comparisons include no difference. The amputation comparisons also do not provide clear statistical evidence of a difference in the unadjusted comparisons. The low counts mean that a lack of strong statistical evidence should not be mistaken for evidence that the groups are equivalent.

These secondary outcomes do not simply confirm or refute the primary result. Clinical cure at follow-up visit 1 is an assessment at a defined early follow-up, whereas reinfection and amputation capture later events with different clinical meanings. A pattern across outcomes can be informative, but differences in endpoint definition, timing, and event frequency prevent treating them as interchangeable measures of one underlying result.

The registry record does not report adjusted secondary analyses, a multiplicity strategy, or a detailed analysis plan. When multiple outcomes and comparisons are examined, the chance of at least one apparently unusual result can increase. Unadjusted secondary results therefore carry less weight than a prespecified primary comparison and are best viewed as descriptive or exploratory unless the analysis plan establishes otherwise. Their interpretation should also account for the small number of events and the reported uncertainty, rather than relying on isolated p-values.

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

• Number of Patients With Re-infections
• Time to Clinical Response
• Percent of Subjects That Had an Amputation Associated With the Target Ulcer

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: clinical cure was either recorded or not recorded for each participant at follow-up visit 1. A group percentage describes the proportion meeting the outcome. The comparison is based on the observed group frequencies, with the placebo-sponge group as the control for the gentamicin-sponge comparison and the no-sponge group as the control for the other comparison.

What the group percentages describe

The posted primary outcome percentages are 69% for gentamicin sponge, 41% for placebo sponge, and 36% for no sponge. These values describe the outcome in the analysis population at a particular visit. They are not percentages of improvement from baseline, and they do not represent outcomes at every follow-up visit. The registry record defines clinical cure as resolution of all clinical signs and symptoms of infection.

A risk difference compares the outcome proportions by subtraction, expressed on the probability scale. A positive risk difference means the outcome was more frequent in the first named group than in the control group; a negative value means it was less frequent. The posted comparison for gentamicin sponge versus placebo sponge is in the positive direction. The comparison against no sponge is in the negative direction as encoded in the record’s comparison, where the active group is contrasted with the control. The registry also posts risk ratios and odds ratios for the primary comparisons. In general, a risk ratio compares event probabilities as a ratio, while an odds ratio compares event odds. These measures use different scales and should not be treated as interchangeable.

How to read a p-value

A p-value is a measure of how compatible the data are with a specified statistical model, commonly one that assumes no group difference. Smaller values indicate greater incompatibility with that model, conditional on the assumptions and analysis used. The primary gentamicin-versus-placebo comparison has p < 0.001, while the comparison with no sponge has p = 0.388. Neither value measures the probability that a treatment effect is real, and neither indicates the probability that the observed result will recur in another study.

The posted comparison p-values are unadjusted. The registry record does not report whether the trial’s prespecified analysis used an adjustment, a different test, covariate adjustment, or another method. The posted record also does not provide a statistical analysis plan against which to compare the displayed comparisons. Therefore, the comparisons should be read as the unadjusted results posted in the registry record, not assumed to reproduce an undocumented primary analysis.

Confidence intervals and uncertainty

A confidence interval describes the range of estimates reasonably compatible with the data under a statistical procedure. Narrower intervals indicate greater precision; wider intervals indicate greater uncertainty. For a risk difference, an interval spanning zero includes values that correspond to no difference. The reported interval for the gentamicin-versus-placebo comparison lies on the positive side of no difference, while the interval for gentamicin versus no sponge spans no difference. These interval patterns accord with the respective unadjusted p-values.

In general, a confidence interval does not include every source of uncertainty. It reflects sampling variability under the method used, but does not automatically account for bias, outcome misclassification, missing-data assumptions, or multiplicity. The registry record does not report the interval-construction method or whether the intervals correspond to an adjusted analysis.

Analysis population and comparison structure

The modified intent-to-treat population included randomized participants under the inclusion and early-termination conditions described in the registry record. This is not identical to a statement that every randomized participant contributed a primary outcome. The record does not report the number excluded under the early-termination condition or give a flow of participants through the analysis. The primary outcome group sizes are 257, 129, and 131.

Random allocation is intended to make treatment groups comparable on average, but it does not guarantee balance in every trial, and the registry record does not post baseline characteristics for this outcome summary. The record describes double masking, but does not specify who was masked or how masking was handled for participants assigned to no sponge. Such details matter when judging the potential for differences in care or outcome assessment.

General statistical context: estimates from a randomized comparison remain subject to uncertainty, and the reliability of interpretation depends on design, conduct, analysis, and reporting. A p-value, point estimate, and interval provide different information and are best read together. The posted primary results provide group percentages, unadjusted comparisons, and confidence intervals, but the registry record does not report the full prespecified analysis details needed to determine whether other planned analytical choices would change their interpretation.

11. Confidence Intervals and Precision

The primary comparison of gentamicin sponge with placebo sponge has a confidence interval that remains on the positive side of no difference. In practical terms, the interval supports a higher cure percentage in the gentamicin-sponge group within the range of estimates compatible with the posted analysis. Its p-value is p < 0.001. The interval nevertheless represents uncertainty about the size of the difference; it does not make the point estimate exact.

For gentamicin sponge versus no sponge, the reported confidence interval spans both sides of no difference, and the unadjusted p-value is 0.388. This indicates substantially less precision about the direction and size of the contrast. The result is compatible with no difference as well as with differences in either direction under the interval’s procedure. It should not be read as establishing equivalence.

The primary group sizes were 257, 129, and 131. As a general statistical principle, the precision of a binary-outcome comparison depends on the number of participants and the distribution of outcomes in each group. Unequal group sizes can also affect precision. The registry record does not report a confidence-interval method or explain whether the primary results were adjusted for other variables.

Intervals describe sampling uncertainty under their statistical assumptions; they do not quantify uncertainty from all possible sources. Missing outcome data, measurement choices, bias, or multiple comparisons can affect interpretation, and the registry record does not report enough detail to assess all of these issues. The posted intervals are therefore useful for judging precision of the stated comparisons, but they are not a complete account of every uncertainty surrounding the results.

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 figures are illustrations based on the observed effect, not a record of the trial’s original design calculation. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect. For these binary outcomes, the figures are participants per arm, not total participants or total events.

The 80% power column means the illustrated number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect is the true effect and the model assumptions hold. The 90% power column has the analogous meaning for a 90% chance. These are design-planning quantities, not guarantees about what a study will find. They are not observed power.

Planning for 100% of the observed primary effect in the gentamicin-versus-placebo comparison gives 50 participants per arm for 80% power and 66 participants per arm for 90% power. Planning for 75% of the observed effect gives 90 and 119 participants per arm, respectively; planning for 50% gives 202 and 270 participants per arm. The no-sponge comparison yields much larger illustrations because its observed contrast is smaller. The record does not report whether the original trial was designed around either comparison or these assumptions.

Smaller effects require more participants to detect with the same target power and significance level. The planning figures also rely on equal allocation, unlike the trial’s reported 2:1:1 allocation across three groups. They should therefore be read as hypothetical two-arm planning scenarios, not as a reconstruction of the trial’s design or an assessment of its achieved power.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.411; treatment proportion p₁ = 0.689; average p̄ = 0.550.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7036 = 1.3790.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6756 = 0.5686.
4. n = (1.3790 + 0.5686)² / (0.2779)² = 49.1, rounded up to 50 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
p0 <- 0.410852713178295                          # control proportion
p1 <- 0.688715953307393                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2447172)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 50 (80% power), 66 (90% power)
 75% of observed effect: n per arm = 90 (80% power), 119 (90% power)
 50% of observed effect: n per arm = 202 (80% power), 270 (90% power)
power.prop.test: 49.1 
Simulated power at n = 50 per arm: 0.823 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 record lists one primary outcome and multiple secondary outcomes, with comparisons involving more than one control group. It does not report a multiplicity-adjustment procedure or explain how the family of outcomes and comparisons was handled. When several hypotheses are tested, the probability of observing at least one small p-value by chance can rise. This general concern does not determine the result of any particular comparison, but it makes unadjusted secondary p-values less conclusive.

The record does not report an interim-analysis plan, stopping rules, or whether any interim looks at accumulating outcome data were conducted. It also does not report the trial’s prespecified statistical analysis plan, so it is not possible to assess whether the posted analyses match all planned methods or whether additional prespecified analyses were intended.

The primary analysis population is described as modified intent-to-treat, with inclusion based on randomization and treatment receipt for the sponge groups, and an early-termination exclusion before follow-up visit 1. The record does not give the number of participants excluded by this rule, the number with missing primary outcome data, or the reasons for missingness. The method used to handle missing outcomes is not reported in the registry record. The posted outcome denominators are therefore important to the interpretation, but the registry information does not fully trace participants from randomization to analysis.

The registry record also does not report sensitivity analyses for missing data, imputation procedures, or alternative analysis populations. Without these details, it is not possible to determine how robust the primary result is to different assumptions about participants whose outcomes were not included. These omissions are reporting limitations, not evidence that a particular analysis or adjustment was or was not performed outside the posted record.

In general, multiplicity and missing-data methods should be specified before results are examined because they affect how uncertainty and statistical evidence are interpreted. The posted unadjusted comparisons can be read as reported, but their inferential context is incomplete without the prespecified analysis and data-handling details.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infected skin ulcer (3.8%), cellulitis (3.1%), osteomyelitis (2.3%), skin ulcer (2.3%), deep vein thrombosis (2.3%).

The registry reports serious adverse events among 42 of 260 participants at risk in the gentamicin-sponge group, 26 of 129 in the placebo-sponge group, and 19 of 131 in the no-sponge group. Deaths were reported for 3, 1, and 0 participants, respectively. These are counts within the stated safety denominators; the denominators differ from the primary outcome group sizes in the gentamicin-sponge group.

The most frequently listed serious-event terms include infected skin ulcer at 3.8%, cellulitis at 3.1%, osteomyelitis at 2.3%, skin ulcer at 2.3%, deep vein thrombosis at 2.3%, and cardiac failure at 1.6%. These terms describe events recorded in the registry, not necessarily events judged to have been caused by a study treatment. The record does not provide a treatment-relatedness breakdown for the group totals or detailed event-level narratives.

Counts should be read alongside the number at risk and the definitions and collection procedures, which are not fully detailed in the registry record. The figures alone do not establish comparative safety or causation, and small differences in counts should not be interpreted as proof of a treatment effect.

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

The primary result shows that the recorded clinical-cure percentage at follow-up visit 1 was higher in the gentamicin-sponge group than in the placebo-sponge group: 69% compared with 41%. The unadjusted comparison has p < 0.001, and its reported confidence interval lies on the positive side of no difference. This is the clearest statistical signal in the posted primary results.

The comparison of gentamicin sponge with no sponge is less conclusive. The posted cure percentage was 36% in the no-sponge group, and the unadjusted comparison has p = 0.388 with a confidence interval spanning no difference. This does not establish that the groups are equivalent; it indicates that the comparison is imprecise and does not provide strong statistical evidence of a difference in the posted analysis.

The result applies to the trial’s defined population, care context, outcome definition, and follow-up time. Each group received systemic antibiotic therapy and standard ulcer care. The data therefore address the addition of a topical sponge within that shared treatment context, not the effect of gentamicin sponge as a replacement for systemic antibiotics or standard care.

The primary outcome is a clinical-cure measure at one follow-up visit. It does not alone describe later recurrence, time to response, amputation, or the durability of cure. Some secondary outcomes are posted, but their small event counts and unadjusted nature limit the strength of conclusions that can be drawn from them. The result also does not establish the mechanism behind the observed differences or explain why the placebo and no-sponge comparisons differ.

Statistical evidence should not be confused with a recommendation or a guarantee about an individual outcome. The registry record does not provide enough information to assess every potential limitation, including the full missing-data approach and prespecified analysis procedures. Interpretation should remain tied to the posted results and their uncertainty rather than extending beyond the measured outcomes and follow-up.

17. Why This Trial Matters Statistically

This trial illustrates why comparator choice matters. Gentamicin sponge was evaluated both against a matching placebo sponge and against no sponge, while systemic antibiotics and standard ulcer care were shared across the groups. Those are distinct contrasts: one controls for the presence of a sponge, while the other does not. The primary results show different statistical patterns for the two comparisons, so the comparator should always be clear when interpreting a treatment estimate.

It also demonstrates why effect estimates and uncertainty belong alongside p-values. The placebo comparison has a small unadjusted p-value and an interval on one side of no difference, while the no-sponge comparison has a larger p-value and a wider, less decisive interval pattern. A single significance label would obscure that distinction and could encourage an overly broad conclusion.

The trial further shows the limits of a binary endpoint. A clinical-cure percentage at a specified visit is easy to interpret, but it does not capture the full trajectory of symptoms, time to response, or later events. The registry lists additional outcomes that could add context, yet not all of their results are posted.

Finally, the record highlights the importance of reporting analysis populations, missing-data methods, multiplicity handling, and the prespecified statistical plan. Those details are central to judging how robustly the results answer the clinical question. Without them, the posted results remain informative but do not provide a complete account of the trial’s inferential framework.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the original sample-size justification, so the rationale for the enrollment target and the intended power for the primary comparisons cannot be assessed. The planning illustrations based on observed effects do not reconstruct the original design. The record also does not report the full statistical analysis plan, including the methods used for the posted comparisons and confidence intervals.

Participant flow and missing outcomes are incompletely described. Although the primary population definition includes an early-termination exclusion, the number excluded, the number with missing outcomes, and the method used to address missing data are not reported in the registry record. This limits assessment of how the analysis population relates to all randomized participants.

The registry describes a double-blind study but does not specify who was masked or how masking was implemented in the no-sponge group. The no-sponge comparator also differs from the placebo-sponge comparator in the presence of a sponge, so the two comparisons have different control conditions. The record does not provide enough detail to determine how these features affected outcome assessment or conduct.

Secondary event counts are small, the analyses are unadjusted, and no multiplicity strategy is reported. Time to clinical response is listed as a secondary outcome, but its result is not reported in the registry record. The primary endpoint is assessed at a defined visit, and the registry summary does not establish the durability of that outcome beyond the assessment or explain the rationale for the outcome definition.

These limitations concern what can be evaluated from the registry record; they do not establish that any specific trial procedure was inadequate. They constrain how broadly and confidently the posted findings can be interpreted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers — NCT02447172.
• Registry record last updated 2021-09-29; status last verified 2021-09.
• Results first posted 2021-08-27.
• 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, double-blind, parallel-group phase 3 study in diabetic patients with at least one infected foot ulcer. Participants received systemic antibiotic therapy and standard ulcer care with daily gentamicin sponge, matching placebo sponge, or no sponge. The planned treatment period was up to 28 days.

The primary outcome was clinical cure at follow-up visit 1, approximately 10 days after treatment ended. Cure was recorded in 69% of the gentamicin-sponge group, 41% of the placebo-sponge group, and 36% of the no-sponge group. The unadjusted gentamicin-versus-placebo comparison has p < 0.001; the comparison with no sponge has p = 0.388.

Reinfection and amputation results are also posted, while time-to-clinical-response results are not reported in the registry record. The record does not report the original sample-size justification, full statistical analysis plan, multiplicity procedure, or missing-data methods.