Randomized Trial Comparing Irrisept to Saline Irrigation for Infection Prevention: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized Trial Comparing Irrisept to Saline Irrigation for Infection Prevention (NCT05402995), a randomized phase 4 study. The primary outcome is Number of Participants Experiencing Surgical Site Infection (SSI).

2. Clinical Question

3. Trial Design

This was a Phase 4, randomized, parallel-group trial with no masking. Its official title describes a prospective randomized comparison of Irrisept and saline irrigation for infection prevention after open tibia fractures. The study focused on Gustilo-Anderson Type III open tibia fractures and planned to compare standard debridement and external fixation with approaches involving Irrisept irrigation, antibiotic-coated nails, or both.

The registry lists six enrolled participants and a status of terminated. The study began on 2022-06-21, with primary completion recorded as 2023-08-31. The registry says termination was due to difficulty enrolling participants. It also states that no one was randomized to the reference/control group. The posted arm counts are 2.0 participants in each of the three groups that received an intervention, and 0.0 in the reference/control group.

The groups differed in both irrigation and fixation approach. One used a spanning external fixator with Irrisept; another used an antibiotic-coated medullary nail with saline; and another used the antibiotic-coated nail with Irrisept. The intended reference group used saline irrigation with a spanning external fixator. Because no control participants were randomized, the observed groups do not provide a direct comparison of each intervention against that intended standard-care reference.

Randomized allocation is listed as the design, but the record does not report the allocation sequence, allocation concealment, or the specific method used to assign participants. Masking is listed as none. Further protocol details, including a planned enrollment target, are not reported in the registry record. The study record does not report a sample-size justification or the reason for the termination beyond difficulty enrolling participants.

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: As study was terminated due to difficulty enrolling participants there was no one randomized to the reference/control group.

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: As study was terminated due to difficulty enrolling participants there was no one randomized to the reference/control group.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Experiencing Surgical Site Infection (SSI), measured over 90 days.

The primary endpoint was the number of participants experiencing surgical site infection, measured over 90 days. The registry describes it as a count of participants with surgical site infections in the total study population. It is a binary outcome at the participant level: each person either experienced the event during the stated timeframe or did not.

In general, infection is used as an endpoint in studies of open-fracture management because it captures a complication the interventions were intended to prevent. Counting affected participants can be straightforward to interpret, but the count alone does not show how precisely an intervention effect has been estimated. A comparison also requires interpretable information from the groups being compared.

The posted primary outcome counts are 0.0 in each group with participants: spanning external fixation with Irrisept, antibiotic-coated medullary nail with saline, and antibiotic-coated medullary nail with Irrisept. Each of those groups had 2.0 participants. The reference/control group had 0.0 participants, and the registry explicitly notes that no one was randomized to it. The zero counts therefore describe only the small groups with posted participants; they do not establish that infection risk was equivalent across approaches or that a comparative effect can be estimated.

The registry’s primary outcome concerns surgical site infection, while the study summary discusses deep infection. The posted primary outcome description does not provide further criteria for classifying an infection as deep, nor does it give additional diagnostic or adjudication details. Such details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is listed as randomized, parallel, and unmasked. In general, random allocation is intended to make treatment groups comparable, on average, with respect to factors that may affect an outcome. That protection depends on participants actually being allocated to the groups in a way consistent with the randomization process. The registry notes that no one was randomized to the reference/control group, and the posted group sizes are very small. The record does not report the allocation sequence, concealment procedures, or any further details of how randomization was carried out.

What does a binary endpoint tell us?

The primary outcome counts participants who experienced surgical site infection within 90 days. This is a binary endpoint because each participant is classified according to whether the event occurred during the defined period. In general, a group’s count can describe what happened among its participants, while an event proportion can describe the observed frequency. A comparison between groups requires data from the groups being compared and an estimate of uncertainty. The posted results give counts but no confidence intervals, p-values, or other comparative analyses.

With sparse data, especially when a group has few participants or no observed events, estimates can be highly uncertain. A zero count is compatible with a range of possible underlying event risks; it does not by itself establish absence of risk. General methods for binary outcomes can produce estimates and intervals, but the choice of method depends on the study design and data. No method for estimating the primary treatment effect is reported in the registry record, and no two-arm comparison is available against a control group with zero participants.

Why does the missing control group matter?

The intended reference group was standard operative debridement with saline irrigation and a spanning external fixator, followed by definitive fixation later. Since it had 0.0 participants, the registry’s posted outcome counts cannot estimate a difference between that approach and any intervention group. The study also included groups that varied in both irrigation solution and fixation method. In general, a comparison of groups that differ in more than one treatment feature cannot isolate the contribution of each feature without an appropriate design and analysis. The registry reports no analysis that separates these effects.

What can the planning illustration establish?

The record describes a sample-size planning illustration based on the observed effect. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that a treatment effect exists. The actual planning counts and the specific fractions are not reported in the registry record. Because the control group had no participants and no two-arm comparison is estimable, the record does not support treating a planning illustration as a reliable measure of the trial’s ability to detect an effect.

In general, a confidence interval communicates a range of effect estimates compatible with the data and the statistical method, while a p-value assesses compatibility with a specified null hypothesis under that method’s assumptions. Neither is posted for the primary outcome. Their absence means the reader cannot assess a reported inferential estimate; it should not be replaced by a conclusion drawn from the zero event counts.

How should treatment variation be understood?

The four planned approaches combine irrigation and fixation features in different ways: saline with spanning external fixation, Irrisept with spanning external fixation, saline with an antibiotic-coated medullary nail, and Irrisept with an antibiotic-coated medullary nail. The posted results contain participants only in the latter three approaches. This arrangement might invite questions about separate treatment effects or an interaction between irrigation and nail use. However, the registry does not report a factorial analysis, an interaction analysis, or any other model for those questions. Such analyses cannot be assumed from the arm descriptions alone.

The record lists two outcome measures, including the primary infection outcome and a secondary outcome of fracture healing. It reports one secondary outcome, but no results for fracture healing are included in the registry record for the registry record. No statistical analysis is listed for either outcome. The analytic population, handling of missing observations, and approach to multiplicity are not reported in the registry record.

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("Spanning External Fixator With Irrisept Irrigation", "Antibiotic-coated Medullary Nail With Saline Irrig", "Antibiotic-coated Medullary Nail With Irrisept Irr")
n      <- c(2, 2, 2)
events <- c(0, 0, 0)
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  Spanning External Fixator With Irrisept Irrigation  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Antibiotic-coated Medullary Nail With Saline Irrig  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Antibiotic-coated Medullary Nail With Irrisept Irr  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the number of participants with fracture healing as a secondary outcome, in addition to the primary surgical site infection outcome. It reports two outcome measures in total and one secondary outcome, but results for fracture healing are not reported in the registry record. The number of posted analyses is 0. No plan for choosing among multiple outcomes, adjusting for multiple comparisons, or identifying a primary analysis is reported in the registry record.

Multiplicity matters in general when a study evaluates several outcomes, treatment contrasts, or analysis choices. Conducting many tests can increase the chance of finding an apparently notable result by chance. A prespecified analysis plan can clarify which comparisons are primary and how other analyses should be interpreted. The registry record does not report such a plan, and there are no posted inferential analyses to evaluate.

The record does not describe how missing outcome information was handled, whether all enrolled participants had complete follow-up through 90 days, or how participants were included in any analysis population. It also does not report an intention-to-treat analysis or another defined analysis population. Since no analyses are posted, it is not possible to determine how the primary endpoint was analyzed or whether participants with incomplete follow-up were excluded or otherwise accounted for.

In general, missing-outcome methods matter because estimates may be biased if missingness is related to treatment or outcome. The available registry entries do not establish whether such missingness occurred in this trial. The reason given for termination is difficulty enrolling participants; it does not by itself describe the completeness of follow-up or the handling of missing measurements.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: amputation (50.0%).

The serious adverse event figures are descriptive counts by group. The spanning external fixator with Irrisept group had 2 participants at risk and 0 serious adverse events. The antibiotic-coated medullary nail with saline group had 2 participants at risk and 1 serious adverse event. The antibiotic-coated medullary nail with Irrisept group had 2 participants at risk and 0 serious adverse events. The standard-care reference/control group had 0 participants at risk and 0 serious adverse events.

The registry lists Amputation at 50.0% among the serious adverse event terms. This is a listed term, not an estimate of comparative treatment risk. The record does not report enough detail to determine the event’s timing, cause, relationship to treatment, or whether it corresponds to a particular participant beyond the group-level serious-event count. No deaths are listed.

In general, safety counts from very small groups are difficult to compare: one event can have a substantial influence on the observed pattern, and no control participants means the intended control comparison cannot be made. The figures should therefore be read as the adverse events recorded in these groups, not as proof that one approach is safer or more harmful than another. The registry lists 0 other adverse events in each group with participants.

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

The results establish what was recorded among the enrolled participants: 2.0 participants in each of three intervention groups, 0.0 in the intended standard-care control group, and 0.0 surgical site infection counts in each group with participants. The study was terminated, with difficulty enrolling participants identified as the reason. Those details describe the available record; they do not answer the intended comparative question.

The results do not establish that the approaches have the same infection outcomes. A lack of observed infections in small groups does not rule out infections in a larger population, and the missing control group prevents comparison with the intended standard-care approach. The record also does not establish whether Irrisept independently affects infection outcomes, whether an antibiotic-coated nail independently affects them, or whether their combination has a distinct effect. No comparative analyses or uncertainty intervals are posted.

The safety counts likewise do not establish a difference in risk. One serious adverse event was recorded in the antibiotic-coated medullary nail with saline group, while none were recorded in the other intervention groups. The number of participants is too limited for these counts to support a dependable treatment comparison, and the record provides no analysis of the serious event or its relation to treatment.

In general, a randomized trial can support causal comparisons when allocation and follow-up are adequate and when the available data permit the planned analysis. The registry record identifies the study as randomized, but no participants entered the reference group and no statistical analyses are posted. Consequently, the observed counts are not a basis for deciding whether any approach changes infection or fracture-healing outcomes. The record also does not report fracture-healing results.

The study’s intended question remains clinically important, but the posted results are limited evidence. They can be used to understand the small amount of outcome information recorded and the enrollment difficulty that led to termination. They cannot be treated as proof of benefit, lack of benefit, equivalence, or comparative safety.

14. Why This Trial Matters Statistically

This trial illustrates why a randomized design label is not enough to guarantee an interpretable randomized comparison. The record lists randomization, yet no participants were randomized to the planned reference/control group. As a result, the intended contrast with standard care is unavailable. This is a design and estimation issue, not merely a matter of whether the observed counts look favorable.

The very small group sizes also show why event counts need context. Each of the three intervention groups had 2.0 participants, and each had a posted surgical site infection count of 0.0. In general, such sparse observations provide little precision about an event rate. Without a comparison estimate and a measure of uncertainty, the counts cannot distinguish between genuinely low risk and limited information about the risk.

The study also raises an important question about interventions that combine multiple treatment features. Irrigation solution and fixation approach varied across the planned groups. To separate their contributions, a suitable design and analysis must be specified and supported by enough data. The registry record does not report an analysis that estimates separate or combined effects.

Finally, the trial demonstrates the difference between planning assumptions and achieved evidence. A sample-size illustration is described, but the trial terminated because of difficulty enrolling participants, and no control participants were enrolled. Planning calculations cannot substitute for observed comparative results, and they are not observed power. For clinical researchers, the record emphasizes the value of reporting enrollment, allocation, outcome definitions, analysis plans, and uncertainty in a way that makes the limits of the evidence clear.

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 principal limitation is that the intended reference/control group had 0.0 participants. This prevents a direct comparison against the planned standard-care approach. The three groups with participants each had 2.0 participants, so the posted results are also highly limited in how precisely they describe outcomes beyond those observed individuals.

The trial was terminated because of difficulty enrolling participants. The registry record does not report a target enrollment, a sample-size justification, or further details about the circumstances of termination. It also does not report the allocation process beyond identifying the study as randomized, nor does it give details about outcome adjudication or infection classification beyond the primary outcome description.

No inferential analyses are posted. There are no treatment-effect estimates, confidence intervals, p-values, or reported analyses of the secondary fracture-healing outcome. The registry record does not report the analysis population, missing-data methods, or a plan for multiplicity. Thus, neither the primary outcome nor the safety counts can be interpreted through a reported comparative model.

The posted groups differ in irrigation and fixation approach, which limits attribution of any observed pattern to one treatment component. The absence of participants in the reference group compounds that limitation. The serious adverse event listing gives a group-level count and a term, but does not describe timing, attribution, or clinical context in enough detail for a treatment-specific interpretation. These constraints limit both efficacy and safety conclusions from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Randomized Trial Comparing Irrisept to Saline Irrigation for Infection Prevention — NCT05402995.
• Registry record last updated 2024-04-24; status last verified 2024-03.
• Results first posted 2024-04-24.
• 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

The registry describes NCT05402995 as a Phase 4 randomized, parallel-group trial with no masking, studying Irrisept and saline irrigation for infection prevention after Gustilo-Anderson Type III open tibia fractures. Six participants were enrolled. The study started on 2022-06-21, had primary completion recorded as 2023-08-31, and is listed as terminated because of difficulty enrolling participants.

The primary outcome was the number of participants experiencing surgical site infection within 90 days. The three intervention groups each had 2.0 participants and a posted infection count of 0.0. The standard-care reference/control group had 0.0 participants; the registry states that no one was randomized to it. One serious adverse event was recorded in the antibiotic-coated nail with saline group, and no deaths were listed. Fracture healing was listed as a secondary outcome, but its results are not reported in the registry record. No statistical analyses are posted.