Technology That Permits Focal Dose of Antibiotics to be Delivered to Lower Limb(s) of Diabetic Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Technology That Permits Focal Dose of Antibiotics to be Delivered to Lower Limb(s) of Diabetic Patients (NCT02158442), a randomized phase 2 study. The primary outcome is Efficacy of Timentin Delivered by PILP Procedure (Treatment Group) Versus Intravenous Delivery (Control Group) at Reducing Microbiological Load in Subjects With Diabetes, and Significant Wound Infection of the Lower Limb..

2. Clinical Question

3. Trial Design

This was a randomized, open-label, parallel-group Phase 2 study sponsored by Osprey Medical, Inc. The registry record lists enrollment of 15 and a completed status. The study began in 2013-10, with primary completion in 2015-02. Random allocation is reported, but the method used to generate the sequence, conceal assignments, or determine allocation ratio is not reported in the registry record.

The comparison was between a treatment group that received intravenous Timentin before percutaneous isolated limb perfusion and a control group that received standard dosings of intravenous Timentin plus other standard care. Masking is listed as none, so the study is recorded as open-label. The record does not say whether laboratory staff assessing microbiological samples were masked to treatment assignment.

The primary endpoint was assessed at Day 3. The posted outcome gives a count of participants whose microbiological load was reduced among those with analyzable microbiological loads. It reports 5 of 5 analyzable loads with a reduction in the treatment group and 3 of 3 in the control group. The description also states that 1 treatment-group load and 4 control-group loads were not analyzable.

The registry record does not report a statistical analysis plan, a sample-size justification, details of randomization, or procedures for protocol deviations. It lists no posted analyses. The record therefore allows a description of the design and the posted endpoint counts, but does not establish how the investigators intended to estimate the treatment contrast or address uncertainty.

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: Treatment Group: 5 of the 5 analyzable microbiological loads resulted in a reduction. 1 was not analyzable. Control Group: 3 of the 3 analyzable microbiological loads resulted in a reduction. 4 were not analyzable.

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 Efficacy of Timentin Delivered by PILP Procedure (Treatment Group) Versus Intravenous Delivery (Control Group) at Reducing Microbiological Load in Subjects With Diabetes, and Significant Wound Infection of the Lower Limb., measured over Day 3.

The primary outcome concerns reduction in microbiological load in a lower-limb infection. The registry description says that assessment included CFU, infection type and antibiotic sensitivity, with the comparison made over time. The stated assessment time for the primary outcome is Day 3. The posted result is expressed as the number of participants with a reduction, so the reported endpoint is a binary event: reduction versus no recorded reduction among analyzable microbiological loads.

Microbiological measurements can help describe whether the amount or composition of organisms detected in a sample changes after treatment. In general, an endpoint based on a binary event gives an easily interpreted count of participants meeting a defined condition, but it does not show the size of each participant’s change. The registry record does not report the threshold used to classify a load as reduced, the measurement method, the actual CFU values, or a quantitative change from baseline.

Microbiological load is not identical to every aspect of infection or clinical status. The posted primary outcome does not report wound healing, limb salvage, symptoms, or other clinical outcomes. Those outcomes should not be inferred from the microbiological result. The registry record lists one outcome measure and no posted secondary outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and the posted outcome can be read as a randomized comparison with a binary primary result at Day 3. The available record is limited: it gives event counts and analyzability counts, but no posted comparative analysis. The distinctions below explain what those features mean and what cannot be concluded from them.

What does randomization contribute?

The registry record classifies allocation as randomized. In general, randomization is intended to reduce systematic differences between groups at the start of a study by assigning participants through a chance-based process. It does not guarantee that every baseline characteristic will be balanced, particularly in a small study, and the record does not provide baseline characteristics with which to examine balance. The sequence-generation method, allocation concealment, and allocation ratio are not reported in the registry record, so the implementation of randomization cannot be evaluated from the record.

What does the open-label design mean?

The masking field is listed as none. In general, an open-label design means treatment assignment is not masked from participants or study personnel. Knowledge of assignment may influence care, sample collection, assessment, or reporting, depending on how those procedures are conducted. The registry record does not report whether laboratory assessment was masked, whether outcome assessors were independent, or whether the endpoint was determined using a prespecified objective rule. It is therefore not possible to assess the extent to which awareness of treatment could have influenced measurement.

How should the binary outcome be understood?

The endpoint is posted as a number of participants with an event, where the event is a reduction in microbiological load. The reported values are counts among analyzable loads: 5 of 5 in the treatment group and 3 of 3 in the control group. In general, binary outcomes record whether a condition was met, rather than the magnitude of change. The posted counts do not show the starting or ending microbiological measurements, the amount of reduction, or the classification threshold. Those details are not reported in the registry record.

A comparison of binary outcomes can be expressed using measures such as a difference in event proportions or a relative measure. These measures require clear group denominators and a specified analysis population. No comparative estimate is posted. No interval estimate or hypothesis-test result is listed, so the registry record does not show the uncertainty around a between-group contrast.

Why does analyzability matter?

The endpoint description states that 1 treatment-group load and 4 control-group loads were not analyzable. In general, missing or unusable outcome measurements can reduce the information available for comparing groups. The consequences depend on why measurements are unavailable and on how the analysis handles them. For example, an analysis limited to analyzable measurements may differ from an analysis that accounts for every randomized participant. The registry record does not report reasons for non-analyzability, imputation procedures, sensitivity analyses, or a prespecified rule for handling these observations. It is not possible to determine whether the unavailable measurements could have altered the interpretation.

What can be said about statistical significance?

No statistical analysis is posted for the primary outcome. A result described as statistically significant or not statistically significant requires a reported inferential analysis and its assumptions; the registry record does not provide one. In general, a p-value addresses compatibility between data and a specified null model, whereas a confidence interval communicates uncertainty around an estimate. Neither substitutes for considering the size and clinical relevance of an effect. Here, no such estimates are reported, so statistical significance and precision cannot be assessed from the registry record.

What do planning calculations represent?

In general, sample-size calculations are planning illustrations for a future or planned study under specified assumptions. They are not observed power and do not establish the probability that this completed study detected an effect. The registry record describes planning assumptions that include a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. These assumptions describe the planning calculation, not necessarily the trial’s original design or its analysis. The record does not report the trial’s own sample-size justification or protocol-level design assumptions.

Because the registry record does not report a sponsor analysis or recalculated inferential results, there is no competing analysis to interpret. The primary evidence available in the record is the outcome description and its counts. Any reader should distinguish that descriptive evidence from an inferential comparison that is not reported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment Group", "Control Group")
n      <- c(5, 3)
events <- c(5, 3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment Group  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  Control Group  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no posted secondary outcomes. It also lists no posted analyses. A multiplicity strategy—how a study handles the increased chance of false-positive findings when testing multiple outcomes or hypotheses—is not reported in the registry record. With no posted inferential tests, the record does not show whether any adjustment for multiple comparisons was planned or performed.

Missingness is important for the primary endpoint. The outcome description states that 1 treatment-group microbiological load and 4 control-group loads were not analyzable. The reasons, timing, and handling of these observations are not reported in the registry record. It is also not reported whether the posted counts include all randomized participants, all participants who began treatment, or another analysis population. The posted result should therefore be read as a count among analyzable loads, not assumed to represent a complete analysis of everyone randomized.

In general, an intention-to-treat analysis retains participants in their assigned groups, while other analysis populations may exclude participants according to specified criteria. The registry record does not state which population was used for the primary endpoint or define any such criteria. It does not report imputation, sensitivity analyses, or a missing-data model. As a result, the robustness of the endpoint comparison to unavailable measurements cannot be evaluated.

The analysis plan, including the statistical methods chosen for the primary outcome, is not reported in the registry record. The record also does not report interim analyses or stopping rules. These absences limit assessment of how the endpoint and missing observations were handled, rather than demonstrating that any particular method was or was not used.

12. 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 serious adverse event terms

Serious events with the highest arm-level rate: mca infarct (14.3%).

The registry safety figures show serious adverse events among participants at risk in each group. In the treatment group, 0 serious adverse events are recorded among 6 at risk. In the control group, 1 serious adverse event is recorded among 7 at risk. The record lists 0 other adverse events in each group. These are descriptive safety counts; the registry record does not report a comparative safety analysis or an uncertainty estimate.

The registry’s top serious-event term is MCA Infarct, listed as 14.3%. The term is presented as the top serious term; the registry record does not provide further event details in the posted description, and the term should not be assumed to capture every aspect of the event. Death counts are not reported in the registry record.

In general, adverse-event counts should be interpreted in light of the population monitored, the observation period, event definitions, and completeness of reporting. The record gives at-risk counts, but does not describe the safety follow-up period, severity grading rules, causality assessment, or whether events were actively solicited. These safety counts do not establish that an event was caused by a treatment, and they do not provide a precise estimate of comparative risk.

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

The primary result supports a narrow descriptive statement: among the microbiological loads that were analyzable, the registry records reductions in both the treatment and control groups at Day 3. The result does not provide a reported effect estimate comparing those groups. It therefore does not establish how large any difference may be, how precise an estimate would be, or whether a statistical test supports a difference.

The result also does not show that the two approaches are equivalent. In general, equivalence requires a prespecified margin and an analysis designed to test whether the uncertainty around the group contrast lies within that margin. Such a margin and analysis are not reported in the registry record. Likewise, the observed reductions among analyzable loads should not be described as proof that either delivery approach caused the reductions, because the registry record does not report the inferential analysis or measurement details needed to evaluate that claim.

The endpoint captures a microbiological reduction, not a complete clinical outcome. The record does not report a quantitative change in CFU, threshold for reduction, or the specific findings for infection type and antibiotic sensitivity. Nor does this primary result report wound healing, limb salvage, or survival. Those outcomes cannot be inferred from the posted endpoint counts.

The numbers of non-analyzable loads differ between the groups, and the record does not explain why. This limits interpretation because the available endpoint counts may not represent the same completeness of measurement in each group. The registry record also does not identify the primary analysis population or explain how unavailable measurements were handled.

The study is recorded as randomized and open-label, and the endpoint was assessed at Day 3. These features define the context of the observation, but do not overcome the absence of a posted comparative analysis. The appropriate reading is that reductions were recorded for analyzable loads in each group, while comparative efficacy and precision remain unreported in the registry record.

14. Why This Trial Matters Statistically

This trial raises several useful statistical questions in a compact randomized comparison. Its primary outcome is a binary summary of a microbiological assessment, and the registry record distinguishes analyzable measurements from those that could not be analyzed. That distinction highlights an important principle: an outcome count is only interpretable when its denominator, analysis population, and missing-data handling are clear.

The posted counts illustrate why raw proportions alone do not establish a treatment contrast. Both groups have reductions among their analyzable loads, but no comparative estimate or uncertainty measure is reported. In general, statistical interpretation requires attention not only to whether events were observed, but also to the size and precision of the group difference. A descriptive count cannot answer those questions by itself.

The open-label design also makes outcome measurement procedures relevant. Microbiological endpoints can be informed by laboratory methods and classification rules. The record does not provide enough detail to determine how measurements were assessed or whether assessment was masked. For clinical researchers, this underscores the value of reporting measurement methods alongside the endpoint definition and analysis plan.

Finally, the record separates a microbiological outcome from broader clinical outcomes. A reduction in microbiological load may be scientifically informative, but it is not interchangeable with wound healing, limb salvage, or survival. Clear reporting helps readers understand which question a trial addresses and which questions remain unanswered.

The statistical importance of this study record lies less in a definitive comparative conclusion than in the interpretive limits it reveals: missing endpoint measurements, an unreported analysis population, and the absence of inferential results constrain what can be learned from the posted outcome.

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.

The registry record does not report a detailed protocol or statistical analysis plan. Important elements—including sequence generation, allocation concealment, allocation ratio, analysis population, and the method used to compare the primary outcome—are therefore not available for evaluation. The record identifies randomization, but that label alone does not describe how randomization was implemented.

There is limited endpoint detail. The primary description mentions CFU, infection type, and antibiotic sensitivity, yet the posted result gives only whether a microbiological load was reduced. The measurement method, reduction threshold, baseline and follow-up values, and results for the other described microbiological components are not reported in the registry record. These omissions prevent assessment of the magnitude and consistency of microbiological change.

The analyzability of the endpoint is another specific limitation. The record states that 1 treatment-group load and 4 control-group loads were not analyzable, but gives no reasons and no description of their handling. It does not say whether the counts reflect every randomized participant or a defined subset. The effect of unavailable observations on the comparison cannot be assessed.

The study is open-label, with masking listed as none. The record does not clarify whether sample processing or outcome assessment was masked, or how the endpoint classification was made. It also does not report baseline characteristics, treatment adherence, protocol deviations, details of standard care, or the duration of safety follow-up.

Finally, no comparative efficacy analysis, confidence interval, or p-value is posted, and no secondary outcomes or analyses are listed. The record cannot support conclusions about precision, statistical significance, broader clinical outcomes, or the reliability of a group difference. These limitations describe what is unavailable in the registry record; they do not establish that particular procedures were absent from the trial itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Technology That Permits Focal Dose of Antibiotics to be Delivered to Lower Limb(s) of Diabetic Patients — NCT02158442.
• Registry record last updated 2016-09-30; status last verified 2016-08.
• Results first posted 2016-08-03.
• 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

NCT02158442 is a completed randomized, open-label, parallel-group Phase 2 study sponsored by Osprey Medical, Inc. It compared Timentin delivered by percutaneous isolated limb perfusion, following intravenous Timentin, with standard dosings of intravenous Timentin plus other standard care in people with diabetes and significant lower-limb infection. The registry record lists enrollment of 15, a start in 2013-10, and primary completion in 2015-02.

The primary outcome concerned microbiological-load reduction at Day 3. The record reports reductions among 5 of 5 analyzable loads in the treatment group and 3 of 3 in the control group, with 1 and 4 loads, respectively, not analyzable. No comparative analysis is posted, and the analysis population and handling of unavailable measurements are not reported in the registry record. Safety counts include 0 serious adverse events among 6 at risk in the treatment group and 1 among 7 at risk in the control group. The available record supports a descriptive account, but not a quantified inferential comparison.