CO2-Laser Treatment in Patients With Diabetic Infected Foot Ulcers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CO2-Laser Treatment in Patients With Diabetic Infected Foot Ulcers (NCT02677779), a randomized na study. The primary outcome is Bacterial Load.

2. Clinical Question

The clinical question concerns the immediate change in bacterial load following two debridement approaches. The registered primary endpoint is percent change in bacterial colonies from baseline, measured immediately after the end of the procedure. The registry reports group medians and inter-quartile ranges, rather than a mean-based summary.

The posted primary summaries are -99.9, with an inter-quartile range from -100.0 to -90.0, for CO2 laser, and -50.0, with an inter-quartile range from -96.0 to 0.0, for traditional surgery. These summaries describe the per-protocol population; patients with no detectable bacterial load at baseline were excluded. The record does not report an inferential test or a confidence interval for a between-group primary-endpoint comparison, so the posted medians alone do not establish the precision of a treatment contrast.

The registry also identifies pain, fibrin coverage, granulation coverage and bleeding requiring haemostasis as secondary outcomes. A numerical comparison is posted for bleeding requiring haemostasis. The other secondary outcomes are named in the record, but their results are not reported in the registry record.

3. Trial Design

This was a randomized, controlled, parallel-group clinical study comparing CO2-laser debridement with traditional-surgery debridement in patients with diabetic infected foot ulcers. The registry lists the study as open label, with no masking. The phase is recorded as not applicable. The sponsor was Azienda Ospedaliero-Universitaria Careggi.

The registry lists enrollment as 20. For the primary bacterial-load endpoint, the results are based on a per-protocol population that excluded patients without detectable bacterial load at baseline. The posted endpoint summaries give a group size of 8 for CO2 laser and 8 for traditional surgery. The adverse-event record gives 10 at risk in each group, and the bleeding outcome also gives 10 participants in each group. These figures refer to different reported analyses and should not be treated as one common analysis population.

The study began in 2016-01, had primary completion in 2016-03, and is listed as completed. The registry describes the primary measurement as the variation in bacterial colonies from baseline immediately after the procedure. The secondary outcomes include pain measured with the Brief Pain Inventory, ulcer area covered by fibrin, ulcer area covered by granulation, and bleeding necessitating haemostasis.

The registry record does not report the method used to generate or conceal the random allocation, the eligibility criteria beyond the stated population, or details of adherence and follow-up. It also does not report the planned analysis methods for the primary outcome or a protocol-based sample-size justification. Those design features therefore cannot be assessed from the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Per-protocol analysis: patients with no detectable bacterial load at baseline were excluded.

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 Bacterial Load, measured over Percent change in bacterial colonies from baseline. Variation from baseline and immediately after the end of procedure..

The primary endpoint is percent change in bacterial colonies from baseline, assessed immediately after the end of the debridement procedure. It is intended to quantify the immediate change in bacterial load following treatment, rather than a later clinical outcome. The registry specifies a median and inter-quartile range as the summary measures.

The reported median is -99.9 for CO2 laser, with an inter-quartile range from -100.0 to -90.0. For traditional surgery, the median is -50.0, with an inter-quartile range from -96.0 to 0.0. A negative percent change represents a decrease relative to baseline; more negative values indicate a larger decrease in this measure. The summaries show the distribution's center and middle spread in each group, but do not by themselves quantify the uncertainty in a between-group difference.

The endpoint population is per protocol. Patients with no detectable bacterial load at baseline were excluded, as their bacterial-load change could not be represented in the stated way. The registry does not report further details about baseline measurement, laboratory procedures, handling of values below detection, or the statistical analysis used to compare groups. Those details matter to interpreting how consistently the endpoint was measured and how the group results should be contrasted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Why report a median and inter-quartile range?

General: The median is the middle value after observations are ordered. It is less affected by extreme observations than the mean, which can make it useful when outcomes are skewed or contain unusually high or low values. The inter-quartile range describes the middle half of the observations, from the lower to the upper quartile. It provides information about spread, but it is not a confidence interval for the median or for a contrast between groups.

The registry specifies the primary outcome as a median with an inter-quartile range. The posted CO2-laser result is -99.9, with the middle range from -100.0 to -90.0; the traditional-surgery result is -50.0, with the middle range from -96.0 to 0.0. The registry does not report an inferential method for comparing these distributions. Comparing the medians informally does not give a formal estimate of the uncertainty in the difference.

What does a between-group estimate add?

General: A contrast expresses the observed separation between groups on a chosen scale. A confidence interval describes uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that includes values compatible with little or no difference may leave substantial uncertainty about the size of the contrast. An interval is not a guarantee that the true value lies within its limits.

For bacterial load, the registry reports group summaries but no between-group estimate, confidence interval, or p-value. Therefore, the primary result cannot be characterized from the registry as a statistically tested group difference. The absence of a reported test is not evidence that the groups are equivalent; equivalence would require a prespecified question and appropriate analysis, neither of which is reported in the registry record.

How should the bleeding comparison be read?

General: For a binary outcome, a risk is the proportion experiencing the event in a group. A risk difference compares those risks on an absolute scale. A risk ratio compares them proportionally, and an odds ratio compares the odds rather than the risks. These measures answer related but different questions. When event counts are limited, estimates can be sensitive to a small change in the observed counts, and relative measures may look particularly large.

The bleeding comparison reports 2 participants with bleeding requiring haemostasis among 10 in the CO2-laser group and 8 among 10 in the traditional-surgery group. The posted risk difference is 0.6, risk ratio is 4.0, odds ratio is 16.0, and unadjusted p-value is 0.007. These measures describe the same observed comparison on different scales. They should not be read as independent confirmations of a finding.

What does “unadjusted” mean?

General: An unadjusted p-value evaluates a particular comparison without correcting for the possibility of multiple comparisons. When several outcomes or tests are considered, the chance of at least one apparently notable result can increase. Adjustments can address that multiplicity, but the approach depends on which outcomes and comparisons were planned and on the analysis strategy.

The record gives an unadjusted p-value for bleeding, while no adjustment strategy is reported. It also identifies several other secondary outcomes. The p-value should therefore be treated as an unadjusted result rather than as a result that accounts for testing across the outcome set. The registry record does not report a prespecified multiplicity procedure or a complete set of secondary-outcome analyses.

How should the planning illustration be understood?

General: A sample-size calculation is a planning tool that estimates how many participants per arm might be needed to detect an assumed effect under specified statistical assumptions. It is not an estimate of the probability that a completed trial detected its effect, and it is not observed power. If planning is based on an effect observed in a small study, that effect may be unstable; considering smaller assumed effects can illustrate how sample-size requirements change as the target effect changes.

The registry's planning illustration uses a two-sided significance level of 0.05, equal allocation, and a normal approximation. It considers 100% of the observed bleeding effect, 75% of that effect, and 50% of that effect. The listed participants per arm for 80% power are 10, 18, and 39, respectively; for 90% power, they are 13, 24, and 52, respectively. These are planning illustrations based on the observed effect, not the trial's own design justification, not a description of the achieved sample size for the primary endpoint, and not observed power. The registry record does not report the sample-size justification used when the study was designed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, but does not report a multiplicity adjustment plan. Multiplicity concerns arise when several outcomes or comparisons are examined: the more tests considered, the greater the chance that at least one result may appear notable by chance. Whether and how to adjust depends on the planned outcome hierarchy and analysis strategy. Those details are not reported in the registry record.

The posted bleeding comparison has an unadjusted p-value of 0.007. It is therefore not a p-value adjusted for the other listed outcomes. The record does not report whether any secondary outcomes were intended to be confirmatory, whether testing was hierarchical, or whether other comparisons were planned. Results for the listed pain, fibrin and granulation outcomes are not reported in the registry record.

Missing-data handling is also not reported in the registry record. For the primary endpoint, the stated per-protocol population excludes patients with no detectable bacterial load at baseline. The record does not describe other exclusions, missing endpoint measurements, reasons for missingness, or any imputation or sensitivity analysis. Thus, the effect of missing or excluded observations on the primary summaries cannot be assessed.

The analysis populations differ across the posted outcomes: the primary endpoint has 8 participants in each group, while the bleeding outcome and adverse-event record each give 10 participants in each group. The record does not explain the relationship between these populations beyond the baseline exclusion specified for the primary endpoint. No reported analyses are listed for the secondary outcomes, and the registry records 0 analyses overall. The precise analysis plan, including any intention-to-treat analysis, is not reported in the registry record.

The record also does not report interim analyses, stopping rules, or a statistical analysis plan. These omissions do not establish that such procedures were absent; they mean their use cannot be assessed from the registry record.

11. Safety Results

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

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 adverse-event record reports 0 participants with serious adverse events among 10 at risk in the CO2-laser group and 0 among 10 at risk in the traditional-surgery group. It reports other adverse events for 3 participants in the CO2-laser group and 8 in the traditional-surgery group, with 10 at risk in each group. The deaths field is not populated, so deaths are not reported in the registry record.

These figures describe the reported counts, not a formal comparison of safety. The record does not report confidence intervals or a statistical test for the adverse-event comparison, and the small group sizes mean the counts alone provide limited information about the range of possible event rates. Zero reported serious events in these groups should not be interpreted as proof that serious events cannot occur.

The serious-event terms are not listed in the registry record. The record also does not provide further detail on event definitions, severity grading, timing beyond the reported outcome information, or how events were collected. The other-adverse-event counts should not be combined with serious events: they are separate categories in the registry record. These safety data allow a description of recorded events in the study, but they do not establish a comprehensive safety profile.

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

The primary endpoint summaries show that the median bacterial-load change was more negative in the CO2-laser group than in the traditional-surgery group. They describe the observed values in the per-protocol population, where patients with no detectable bacterial load at baseline were excluded. The result is immediate and specific to bacterial colonies; it is not a report of longer-term ulcer healing, infection resolution, or another clinical outcome.

The registry does not report a formal primary between-group comparison, confidence interval, or p-value. Consequently, the posted medians and inter-quartile ranges do not establish how precisely the groups differ or whether a prespecified statistical criterion was met. They also do not demonstrate equivalence or lack of equivalence. A complete interpretation would require the planned analysis, treatment of exclusions and missing observations, and an inferential estimate for the primary contrast.

The bleeding outcome has a reported unadjusted comparison, but it is a secondary result and is not adjusted for multiple outcomes. It addresses bleeding requiring haemostasis during the procedure, not bacterial load. The record does not provide numerical findings for the other listed secondary outcomes, limiting conclusions about the broader set of measured domains.

The registry describes a randomized and open-label study, but does not report allocation procedures, masking of outcome assessment, or detailed measurement methods. Those unreported features affect how the results can be appraised. The findings should therefore be understood as a small set of posted group summaries and event counts, accompanied by important gaps in inferential reporting. They do not, on their own, establish that either procedure is superior or inferior overall.

13. Why This Trial Matters Statistically

This study raises several statistical issues that are common in small clinical comparisons. Its randomized, parallel-group design places two debridement approaches side by side, while the primary endpoint is a quantitative change in bacterial colonies assessed immediately after treatment. The registry reports medians and inter-quartile ranges, a useful descriptive choice for an outcome that may not be well summarized by a mean. However, descriptive summaries are not a substitute for a prespecified between-group estimate with uncertainty.

The population used for the primary endpoint is particularly important. The per-protocol analysis excludes patients with no detectable bacterial load at baseline, and the group sizes for that endpoint are 8 in each arm. Results in this selected population may not describe all randomized participants. Without a reported analysis population flow or sensitivity analysis, readers cannot determine how exclusions affect the comparison.

The registry also illustrates why statistical evidence should be interpreted by outcome hierarchy. A secondary binary outcome has an unadjusted p-value, but the primary endpoint has no posted inferential comparison, and several named secondary outcomes lack numerical results. Considering one result in isolation, without a reported multiplicity plan, can overstate the strength of evidence.

Finally, the planning illustration is based on the observed bleeding effect and displays how assumed smaller effects correspond to larger planning sample sizes. That is useful for illustrating sensitivity to assumptions, but it is not the trial's reported design rationale and is not observed power. The record's missing details about randomization procedures, analysis plans, missing data, and endpoint measurement constrain the statistical conclusions that can be drawn.

14. Limitations

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

The principal limitation of the posted primary result is the absence of a reported inferential comparison. The record gives group medians and inter-quartile ranges but no estimate of the between-group contrast, confidence interval, or p-value. Precision of the contrast therefore cannot be judged from the registry record.

The endpoint population is per protocol and excludes patients with no detectable bacterial load at baseline. The record does not explain other differences between the enrolled population and the primary analysis population, or report sensitivity analyses. The primary endpoint group size is 8 in each arm. The posted results do not establish how exclusions or missing measurements might influence the summaries.

The outcome is measured immediately after the procedure and concerns bacterial colonies. The registry does not report details of the laboratory method, the handling of measurements at detection limits, or the reliability of the measurement process. It also does not provide longer-term primary results. The immediate bacterial-load measure should not be treated as a complete measure of clinical outcome.

The study is listed as open label, and the registry does not report whether outcome assessors were masked. It also does not report allocation generation or concealment methods, eligibility details, adherence, or a statistical analysis plan. These omissions prevent a full assessment of potential bias and analytic choices.

Secondary reporting is incomplete: numerical results are posted for bleeding, but not for the other named secondary outcomes. The bleeding analysis is unadjusted, and no multiplicity approach is reported. Safety counts are available, but details on event definitions and collection are not. Together, these limitations mean the registry supports cautious description of observed results rather than strong comparative conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: CO2-Laser Treatment in Patients With Diabetic Infected Foot Ulcers — NCT02677779.
• Registry record last updated 2016-12-06; status last verified 2016-10.
• Results first posted 2016-12-06.
• 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.

18. Record Summary

NCT02677779 is a completed randomized, open-label, parallel-group study of CO2-laser versus traditional-surgery debridement for diabetic infected foot ulcers. The study began in 2016-01 and reached primary completion in 2016-03. The registry lists enrollment as 20 and identifies Azienda Ospedaliero-Universitaria Careggi as sponsor.

The primary endpoint is percent change in bacterial colonies from baseline immediately after the procedure. The per-protocol results exclude patients with no detectable baseline bacterial load and report medians and inter-quartile ranges for 8 participants in each group. No inferential primary comparison is reported in the registry record.

The registry names pain, fibrin coverage, granulation coverage, and bleeding requiring haemostasis as secondary outcomes. A numerical, unadjusted comparison is posted for bleeding; results for the other named secondary outcomes are not reported in the registry record. Serious adverse events are reported for 0 participants in each group, and other adverse events are reported for 3 participants with CO2 laser and 8 with traditional surgery. The record does not report deaths or a detailed statistical analysis plan.