The Safety and Efficacy of an Antibiotic Sponge in Diabetic Patients With Moderately Infected Foot Ulcers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Safety and Efficacy of an Antibiotic Sponge in Diabetic Patients With Moderately Infected Foot Ulcers (NCT00659646), a randomized phase 2 study. The primary outcome is Number of Participants With a Clinical Cure at Visit 3 (Day 7).

2. Clinical Question

The central comparison is between adding a topical gentamicin-collagen sponge to antibiotic treatment and using antibiotic treatment without the sponge. The endpoint combines clinical response and pathogen eradication, rather than counting either feature alone. The posted primary result reports 0 of 26 participants with a cure in the Gentamicin Sponge group and 3 of 10 in the Levofloxacin group. These counts describe the recorded Day 7 outcome in the analysis population; they do not by themselves establish why participants had different outcomes. The registry record does not report the criteria for a positive clinical response, the pathogen assessment procedures, or additional details on how the modified intent-to-treat population was formed.

3. Trial Design

The registry record describes a randomized, controlled, open-label, parallel-group Phase 2 study. It is listed as completed, with enrollment of 56 participants. The study start is recorded as 2008-04 and primary completion as 2009-05. The sponsor is Innocoll. The registry record does not report the method used to generate the random sequence, how allocation was concealed, or whether participants were assigned in equal numbers.

The two treatment groups were a gentamicin sponge applied into the wound plus levofloxacin, and levofloxacin alone. The arm descriptions specify levofloxacin 750 mg by mouth or intravenously every 24 hours. If ulcer culture results showed resistance to levofloxacin, an alternative antimicrobial therapy could be selected according to susceptibility testing. The brief summary describes both groups as receiving standard daily wound care. Because the study was open label, treatment masking was absent; the registry record does not describe masking of outcome assessors.

The primary outcome was the number of participants with clinical cure at Visit 3, Day 7. Its recorded analysis population is modified intent-to-treat. The reported primary outcome counts are 0 among 26 participants assigned to the Gentamicin Sponge group and 3 among 10 assigned to the Levofloxacin group. The record separately lists safety denominators of 38 for the Gentamicin Sponge group and 18 for the Levofloxacin group. The reasons these analysis denominators differ from the primary-outcome denominators are not reported in the registry record.

The registry lists seven secondary outcomes: positive clinical response at each time point, clinical cure at each visit except Visit 3, pathogen eradication by visit, change in total wound surface area, time to clinical cure, pain assessed by a visual analog scale, and the Lipsky Wound Score. The registry record does not report a detailed statistical analysis plan, sample-size justification, interim analyses, or the procedures used to handle missing outcome data.

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

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: modified intent-to-treat

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With a Clinical Cure at Visit 3 (Day 7), measured over Day 7 of treatment.

The primary endpoint counts participants who met the definition of clinical cure at Visit 3, Day 7 of treatment. The definition requires both a positive clinical response and pathogen eradication. It is therefore a composite clinical outcome: a participant must satisfy both components to be counted as cured. A count endpoint states how many participants met that definition in each treatment group, rather than describing the severity of change in a continuous measurement.

A fixed visit gives the groups a common time point for comparison. In this trial, Day 7 provides an early assessment after treatment began. That timing can make the outcome useful for describing initial response, but it does not describe later status or whether a response was sustained. The registry lists other outcomes, including clinical response at multiple time points, clinical cure at other visits, pathogen eradication, wound area, time to cure, pain, and wound score. Those outcomes address different aspects of response and should not be treated as interchangeable with the primary endpoint.

The primary result is reported for a modified intent-to-treat population. The registry record does not explain which participants were included in that population or how missing assessments were handled. It also does not provide further operational details for determining positive clinical response or pathogen eradication. These omissions limit how fully the endpoint definition and analysis population can be independently interpreted.

7. Results Posted in the Registry

• Levofloxacin: 30.0% (3/10) versus 0.0% (0/26) on control; risk difference 30.0 percentage points (95% CI 1.6 to 58.4); unadjusted two-proportion z-test p = 0.004.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count measure?

The primary outcome is a count of participants meeting a binary definition: each participant either met the clinical-cure definition at Day 7 or did not. A count is easy to connect to the number of recorded outcomes, but counts alone are influenced by how many participants contribute to each group. For that reason, the posted comparison also expresses the results as a risk difference, which compares the proportions with the outcome in the two groups. Here the reported event counts are 0 of 26 and 3 of 10. The reported risk difference is 0.3, with Levofloxacin as the first group in the comparison and Gentamicin Sponge as the reference group.

What does a risk difference mean?

A risk difference is the difference between the observed outcome proportions in two groups. A value of zero represents equal observed proportions; values above or below zero indicate the direction of the difference according to the chosen subtraction order. The registry comparison is oriented as Levofloxacin minus Gentamicin Sponge, so its positive estimate points toward a larger observed proportion in the Levofloxacin group. This is a descriptive contrast between the posted groups, not proof that treatment assignment alone caused the difference. Randomization is intended to support causal comparisons, but interpretation also depends on the conduct of the trial, outcome measurement, follow-up, and analysis population.

How should the confidence interval be read?

A confidence interval describes the range of effect estimates reasonably compatible with the observed data under the statistical method and its assumptions. The reported 95% confidence interval for the risk difference is 0.016 to 0.584. It conveys uncertainty in the estimated difference; it does not mean that 95% of participants had outcomes within those limits. It also does not guarantee that the true effect lies in the interval. The breadth of an interval reflects the precision of the estimate, with wider intervals indicating more uncertainty. In general, estimates based on limited outcome information can be imprecise even when a test produces a small p-value.

What does the p-value add?

The reported unadjusted p-value is 0.004. In general, a p-value evaluates how unusual data at least as discrepant as those observed would be if a specified null hypothesis were true and the statistical model were appropriate. It is not the probability that the null hypothesis is true, the probability that the result is due to chance, or a measure of clinical importance. The registry record does not identify the test or model used for the posted comparison, so the exact assumptions behind that p-value are not described. The term unadjusted also matters: the registry record does not report an adjustment for the family of primary and secondary outcomes.

Why do analysis populations matter?

The primary outcome is identified as modified intent-to-treat. In general, an intent-to-treat approach aims to compare participants according to their randomized groups, while a modified version applies some additional eligibility or outcome-evaluability rule. The meaning of modified can vary, so it cannot be inferred without a definition. The registry record does not state which participants were included, what modifications were made, or how missing Day 7 assessments were treated. The outcome counts are 0 of 26 and 3 of 10; safety outcomes use denominators of 38 and 18. The record does not explain the relationship between these analysis sets.

How should the design affect interpretation?

Randomization supports comparison by reducing the influence of systematic differences in participant characteristics, on average, when allocation and analysis are conducted appropriately. The record identifies the trial as randomized but does not report the sequence-generation or allocation-concealment procedures. Open-label means that masking was absent. For outcomes involving clinical judgments, awareness of treatment can potentially influence assessment or reporting; the record does not say whether assessors were masked. These general design considerations do not show that bias occurred, but they identify features that affect confidence in interpretation.

What can planning calculations tell us?

Sample-size calculations are planning illustrations, not observed trial results and not observed power. The planning approach described for the posted illustrations uses a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect set as a stated fraction of the observed effect. Such calculations explore how a hypothetical future study might be sized under specified assumptions. They do not show that the trial had a particular probability of detecting an effect after it was completed. The registry record does not report the trial's own sample-size justification or the assumptions used to plan enrollment. No numerical planning sample sizes are stated in the registry record.

10. Confidence Intervals and Precision

The primary estimate is a risk difference of 0.3, with a 95% confidence interval from 0.016 to 0.584. The interval is the main posted measure of precision for the comparison. Its lower and upper limits are both above zero, while the range between them leaves uncertainty about the magnitude of the difference. A point estimate gives one summary of the observed contrast; the interval shows that estimates compatible with the data extend across a substantial range.

The primary outcome counts are 0 of 26 in the Gentamicin Sponge group and 3 of 10 in the Levofloxacin group. These denominators are modest and unequal. With few observed outcomes, estimates of proportions and their differences can be sensitive to each outcome, and uncertainty can remain considerable. This is a general statistical feature of binary outcomes with limited event information; it does not establish that any individual record is incorrect.

The 95% confidence interval is not a range of participant outcomes, and it is not a guarantee about the true effect. Under a general frequentist interpretation, the method is designed so that intervals constructed in the same way would cover the underlying parameter at the stated rate over repeated studies, if model assumptions hold. The registry record does not specify the method used to construct this interval, so further details about its assumptions are not available.

The safety denominators differ from the primary outcome denominators, and the registry record does not explain the discrepancy. That makes it important to keep the endpoint-specific populations distinct rather than assuming a common denominator. The confidence interval and p-value address the posted primary comparison; they do not quantify uncertainty for every secondary or safety outcome.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and seven secondary outcomes. The secondary outcomes cover clinical response, clinical cure at other visits, pathogen eradication, wound surface area, time to cure, pain, and the Lipsky Wound Score. Considering multiple outcomes can increase the chance that at least one result appears notable by chance when each is assessed separately. As a general statistical approach, researchers may define a hierarchy, adjust significance thresholds, or treat secondary findings as exploratory. The registry record does not report whether any such approach was planned or used.

The posted p-value for the primary comparison is unadjusted. It should therefore be read as the reported unadjusted result, not as evidence that a multiplicity procedure was applied. The registry record does not provide a complete statistical analysis plan, the planned testing sequence, or details of any interim analyses. It is not possible to determine from the registry record whether the reported outcome or analysis was selected before results were known.

The primary outcome is identified as modified intent-to-treat, but the membership rules for that population are not reported in the registry record. Nor are the number of missing Day 7 assessments, reasons for missingness, imputation methods, or sensitivity analyses reported. Missing-data handling matters because participants without an observed endpoint may differ from those with an observed endpoint. Without these details, the effect of missing outcomes on the primary estimate cannot be assessed.

Overall enrollment is 56, while the primary outcome denominators are 26 and 10. Safety denominators are 38 and 18. The record does not explain why these populations differ, whether participants were excluded from the primary analysis, or how exclusions affected group comparability. These are limitations in the reporting available in the registry record, not evidence by themselves that the analysis was improperly conducted.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% 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 (5.6%), cellulitis (2.6%), tendon rupture (2.6%), hypoglycaemia (2.6%), renal failure (2.6%).

Safety results use denominators of 38 for the Gentamicin Sponge group and 18 for the Levofloxacin group. Serious adverse events affected 5 participants in the Gentamicin Sponge group and 1 participant in the Levofloxacin group. Other adverse events affected 4 participants and 1 participant, respectively. No deaths were reported in either group. These are counts of participants affected as recorded, not counts of all event episodes.

The registry also lists serious adverse event terms with percentages: Infected skin ulcer, 5.6%; Cellulitis, 2.6%; Tendon rupture, 2.6%; Hypoglycaemia, 2.6%; Renal failure, 2.6%; and Wound haemorrhage, 2.6%. The record does not provide participant counts for each listed term or explain whether a participant could contribute more than one term. These percentages should therefore be read as the posted term-level figures, not combined or treated as mutually exclusive categories.

Safety denominators differ from the primary outcome denominators, and the reason is not reported in the registry record. The figures describe the recorded events in these groups; by themselves they do not establish that an event was caused by a treatment or support a complete comparison of safety. Event definitions, severity grading, follow-up duration, and the method used to assess relatedness are not reported in the registry record.

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

The posted primary result is a Day 7 comparison of clinical cure, defined by both positive clinical response and pathogen eradication. The observed counts were 0 of 26 in the Gentamicin Sponge group and 3 of 10 in the Levofloxacin group. The reported risk difference, oriented as Levofloxacin minus Gentamicin Sponge, is 0.3, with a 95% confidence interval from 0.016 to 0.584 and an unadjusted p-value of 0.004. These statistics describe the endpoint, visit, and analysis population reported in the registry.

The result does not establish a general treatment effect across all outcomes, later time points, or patient groups. It does not show whether clinical response or pathogen eradication separately accounted for the composite endpoint, and it does not describe whether any response was sustained. The registry lists additional outcomes, but details of their results are not included in the registry record reported for this analysis. The primary result should not be extended to those measures.

The estimate also does not remove uncertainty. The confidence interval spans a range of possible differences, and the event counts are limited. The record does not explain the modified intent-to-treat population, the difference between primary and safety denominators, or missing-data procedures. Open-label treatment and unreported outcome-assessment procedures are further considerations. These points do not demonstrate that the findings are biased; they limit what can be established from the registry information.

Nor does the result show that the sponge caused an outcome, or explain the mechanism behind the group contrast. Randomization is a useful design feature, but interpretation still depends on how allocation, follow-up, endpoint assessment, and analysis were carried out. The registry record does not report enough detail to assess every one of those features. The defensible conclusion is therefore narrow: the posted Day 7 counts and comparison favor a higher observed clinical-cure proportion in the Levofloxacin group, with the stated statistical uncertainty and reporting limitations.

14. Why This Trial Matters Statistically

This trial illustrates why an endpoint's definition and analysis population are central to interpreting a clinical comparison. Clinical cure required both positive clinical response and pathogen eradication. A count of participants meeting that combined definition answers a specific question at Day 7; it does not stand in for every dimension of wound response or safety. The registry also identifies a modified intent-to-treat population, but does not describe its membership rules, underscoring that an analysis label alone may not fully identify who contributes to a result.

The different denominators are statistically important. Primary outcome counts use 26 and 10 participants, while safety counts use 38 and 18, and overall enrollment is 56. The record does not explain these differences. Readers need to know which participants contribute to each estimate because denominator choice affects the interpretation of counts and proportions. Keeping each outcome's population distinct avoids treating results as if they arose from the same set of participants.

The reported risk difference and its confidence interval also illustrate why an effect estimate should be read together with its uncertainty. The unadjusted p-value is one part of the statistical evidence, but does not express the size or precision of the effect and does not account for multiple testing. With a primary outcome and seven secondary outcomes, the missing information about multiplicity and analysis planning matters when interpreting any collection of results.

Finally, the open-label design and absent details on outcome assessment are relevant to an endpoint that includes clinical judgment. General statistical concepts cannot substitute for trial-specific reporting. Clear descriptions of allocation, endpoint ascertainment, missing data, analysis populations, and planned comparisons would make the result easier to evaluate and reproduce.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific reporting gaps limit interpretation. The registry record identifies the study as randomized and open label but does not report the random-sequence method or allocation concealment. It does not say whether outcome assessors were masked. Because the primary endpoint includes a clinical response assessment, the absence of information on assessment procedures leaves uncertainty about how consistently the endpoint was determined.

The primary outcome counts are reported for a modified intent-to-treat population, but the registry record does not define that population. The outcome denominators are 26 and 10, the safety denominators are 38 and 18, and enrollment is 56; the reasons for these differing figures are not reported. Missing Day 7 assessments, exclusions, and handling of missing outcomes are also not described. These details are necessary to understand exactly which participants contribute to the primary estimate and how incomplete follow-up may affect it.

The registry record does not report a detailed statistical analysis plan, the trial's sample-size justification, interim analyses, or a multiplicity strategy. It also does not identify the method used to calculate the confidence interval or p-value. The p-value is unadjusted. With seven listed secondary outcomes in addition to the primary outcome, the absence of multiplicity information makes it difficult to assess how the full set of comparisons was intended to be interpreted.

The primary endpoint is measured at Day 7, and the result does not establish whether outcomes persisted beyond that visit. The record does not provide further detail on clinical-cure adjudication, pathogen testing, duration of safety follow-up, or adverse-event relatedness. These limits concern information reported in the registry record; they should not be taken as proof that the procedures were not performed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Safety and Efficacy of an Antibiotic Sponge in Diabetic Patients With Moderately Infected Foot Ulcers — NCT00659646.
• Registry record last updated 2022-01-27; status last verified 2022-01.
• Results first posted 2021-08-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00659646 is a completed, randomized, open-label, parallel-group Phase 2 study sponsored by Innocoll. Enrollment was 56. The study start is recorded as 2008-04 and primary completion as 2009-05. It compared a gentamicin-collagen sponge plus antibiotic therapy with antibiotic therapy alone in participants with moderately infected diabetic foot ulcers.

The primary outcome was the number of participants with clinical cure at Day 7, defined as positive clinical response and pathogen eradication. In the modified intent-to-treat population, the reported counts were 0 of 26 in the Gentamicin Sponge group and 3 of 10 in the Levofloxacin group. The posted risk difference was 0.3, with a 95% confidence interval from 0.016 to 0.584 and an unadjusted p-value of 0.004.

The record lists seven secondary outcomes and reports safety denominators of 38 and 18. It does not report the statistical analysis plan, sample-size justification, multiplicity approach, or reasons for the differing analysis denominators.