Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO) (NCT02227446), a randomized phase 3 study. The primary outcome is Number of Clinically Significant Deep Surgical Site Infection (SSI).

2. Clinical Question

The study was designed to compare deep infection outcomes between the powder and standard-care groups. The endpoint description defines deep infection as an infection requiring operative treatment, while superficial infections are those treated without operative intervention. The outcome window is 26 weeks, described in the registry record as six months.

The registry record identifies the study as a prospective, multicenter randomized controlled trial. It also lists pathogen type and bacterial susceptibility and antimicrobial resistance among the secondary outcomes. Those topics address the nature of infections and organisms, rather than replacing the primary question about the occurrence of deep SSI.

The record does not report a primary-outcome estimate comparing the groups, an uncertainty interval, or a test result. Therefore, the clinical question can be described from the design and endpoint, but the posted information does not establish the direction or precision of any treatment-group difference.

3. Trial Design

VANCO is listed as a phase 3, randomized, parallel-group trial with no masking. The registry record describes it as prospective and multicenter. Enrollment is recorded as 1036, and the study status is completed. The recorded study start is 2014-10 and primary completion is 2018-06.

The parallel-group design assigns participants to one of two approaches at fracture fixation: local vancomycin powder in the wound bed before closure, or standard care without local vancomycin powder. The intervention description specifies a maximum dose of 1000mg and allows the powder to be combined with normal saline according to clinical practice. Standard care includes institution-specific treatment for preventing and treating infection.

Random allocation is intended, as a general design principle, to make groups comparable on average with respect to both measured and unmeasured characteristics. That protection depends on how allocation was implemented and maintained; details of the sequence-generation and allocation-concealment procedures are not reported in the registry record. The absence of masking means the record does not describe the trial as blinded. How outcome assessors or other trial personnel handled knowledge of assignment is not reported in the registry record.

The primary endpoint is clinically significant deep SSI during the first 26 weeks after surgery. The record says that infections are determined using CDC guidelines, while also noting a longer observation period than the CDC criteria's stated three-month period. Wound characteristics are also to be evaluated with the ASEPSIS score. The listed secondary outcomes concern pathogen type and bacterial susceptibility and antimicrobial resistance.

The registry record does not report the trial's sample-size justification, the randomization procedures, a statistical analysis plan, interim analyses, or a detailed description of analysis populations. The existence of a completed randomized trial does not itself provide an estimate of the primary treatment contrast; no primary-outcome analysis is listed in 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

Reasons for not completing this period:

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 Number of Clinically Significant Deep Surgical Site Infection (SSI), measured over 26 weeks.

The primary endpoint is the number of clinically significant deep surgical site infections in the first 26 weeks after surgery. The registry describes the infections as determined using CDC guidelines and defines deep infections as those requiring operative treatment. Superficial infections, by contrast, are described as infections treated without operative intervention. The endpoint therefore focuses on an infection category with a specified clinical consequence rather than treating every wound concern as equivalent.

The observation window is 26 weeks, which the registry description also characterizes as six months. It explains that the investigators extended the time frame to help capture more infections, in comparison with the CDC criteria period of three months noted in the record. This makes the endpoint a count of qualifying infections over a defined postoperative follow-up period; it is not described as a time-to-first-event endpoint.

Wound characteristics are also to be evaluated with the ASEPSIS score. The record describes this as a weighted score based on additional treatment, serous drainage, erythema, purulent exudates, separation of deep tissues, isolation of bacteria, and duration of stay. The registry does not report the scoring results or explain how they relate analytically to the primary endpoint.

Deep SSI is relevant to the study question because it is the infection outcome the trial set out to compare after operative fracture treatment. However, the registry record does not provide the group-specific primary endpoint counts or a comparative estimate. The outcome definition and its rationale can be described, but the posted results do not show the magnitude or precision of a treatment-group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Methods determine what a trial comparison means: how participants are assigned, which outcomes count, how follow-up is handled, and how uncertainty is quantified. The registry record identifies random allocation and a parallel-group structure, but does not report many implementation or analysis details. The explanations below distinguish general statistical concepts from the methods documented for VANCO.

What does random allocation contribute?

As a general principle, random allocation aims to balance prognostic factors between groups over repeated assignments. It reduces the risk that treatment assignment is systematically linked to factors that also influence outcome. Randomization does not guarantee that every characteristic will be identical between the groups in a particular trial. Nor does the word “randomized” reveal how the assignment sequence was generated, concealed, or implemented. Those procedural details are not reported in the registry record.

The record describes a parallel design, in which participants are assigned to one of the treatment approaches and followed in that group. It lists no masking. Masking can reduce the influence of treatment knowledge on care decisions, outcome assessment, or reporting, depending on which people are masked. The registry record does not report further information about masking of outcome assessors or trial personnel.

What does the primary outcome count?

The primary endpoint is the number of clinically significant deep SSI during the first 26 weeks after surgery. The record defines deep infection as infection requiring operative treatment and specifies CDC guidelines for determining clinically significant SSI. Because the endpoint is described as a count of infections, a complete interpretation would need to know the group-specific counts and the analysis method used to compare them. Neither is listed as a primary analysis in the registry record.

Counts can be analyzed in different ways, depending on the scientific question and data structure. A simple comparison of proportions addresses whether the chance of at least one event differs between groups. A count model can instead reflect the number of events, especially if a participant can contribute more than one event. A time-to-event method considers when an event occurs and may account for differing follow-up. These are general alternatives, not methods identified for VANCO. The registry record does not report which approach was planned or used.

For count data, a model may need to account for over-dispersion: a situation in which observed variability exceeds what a basic count model assumes. Ignoring over-dispersion can make uncertainty estimates too narrow. Whether it is relevant depends on the data and model. The registry record does not provide the primary outcome data or analysis details needed to assess this issue for the trial.

How should uncertainty be understood?

Generally, a confidence interval pairs an estimated treatment contrast with a range of values compatible with the observed data and the chosen method. It helps readers assess precision, not just whether a result crosses a conventional significance threshold. The registry record does not list an estimate or confidence interval for the primary endpoint. It also does not list a primary-outcome test result. The statistical uncertainty around the treatment contrast therefore cannot be evaluated from the posted record.

A p-value, in general, describes how surprising data at least as extreme as those observed would be under a specified null hypothesis and statistical model. It is not the probability that a treatment works, and it does not measure the size of an effect. Since no primary-outcome p-value is listed, there is no test result to interpret for the main question.

What can a planning illustration say?

Any sample-size planning illustration is not an observed power calculation. The stated assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm; time-to-event illustrations use a total number of events. These are general planning calculations based on their assumptions, not a report of what the completed trial observed or a replacement for its analysis.

The registry record does not report the trial's own sample-size justification. A planning illustration based on an observed effect cannot show that the trial had a specified probability of detecting a clinically meaningful effect. Observed power is not a substitute for an effect estimate and confidence interval; precision is better judged directly from the estimate and its uncertainty, when reported.

What is missing from the statistical record?

The registry lists no analyses and does not reduce the primary outcome's several categories or time points to one comparison. It does not report a statistical analysis plan, an interim-analysis approach, missing-data methods, covariate adjustment, or analysis-population definitions. These omissions limit reproducibility and make it impossible to assess whether the posted data were analyzed according to a prespecified plan. They also prevent a reader from determining whether any analysis accounted for baseline differences, repeated events, or incomplete follow-up.

The clinical endpoint remains interpretable as defined: qualifying deep SSI during the stated follow-up window. But without group results and analysis details, readers cannot estimate its comparative frequency or judge precision, model assumptions, or robustness. The registry description is therefore informative about the intended design and outcome, not a complete statistical report of the primary comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and two secondary outcome topics: pathogen type and bacterial susceptibility and antimicrobial resistance. The primary outcome is noted as having several categories or time points and is not reduced to one comparison. This makes it unclear which specific contrast or contrasts would constitute the main confirmatory test, and the registry does not report a multiplicity strategy.

In general, testing multiple outcomes, categories, time points, or subgroup contrasts can increase the chance of at least one apparently notable finding even when no true effect exists. Methods to address multiplicity may define a hierarchy of outcomes, adjust significance thresholds, or emphasize estimation and uncertainty rather than a collection of isolated tests. These are general options; the registry record does not report which, if any, were used for VANCO. The absence of a listed strategy does not establish that no strategy existed outside the registry record.

Missing-data handling is also not reported in the registry record. For an outcome assessed during 26 weeks of follow-up, a reader would need to know how participants without complete outcome ascertainment were treated and whether follow-up differed between groups. The record does not give those details or report the extent of missing primary-outcome data.

Analysis populations are not described. The registry record does not say whether the primary analysis was intended to include participants according to randomized assignment, treatment received, or another definition. Such choices affect interpretation, especially if assigned treatment and received treatment differ. No analysis is listed to clarify the approach used.

The registry record also does not report interim analyses, stopping guidance, or a statistical analysis plan. These details are important for understanding how outcome comparisons were specified and how decisions were protected against data-driven selection. Without them, and without a primary result, neither multiplicity control nor the handling of missing observations and analysis populations can be assessed.

11. 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: infection (1.2%), abdominal injury (1.0%), venous thromboembolism (vte) (0.6%), nonunion (0.4%), manipulation under anesthesia (0.4%).

The registry's serious-adverse-event summary reports 21 affected participants among 499 at risk in the Control group and 16 among 481 at risk in the Vancomycin Powder group. Deaths are listed as 3 in the Control group and 4 in the Vancomycin Powder group. The other-adverse-event affected field is 0 for each group, with 499 and 481 respectively listed at risk.

These are descriptive registry entries. They do not by themselves establish that an event was caused by the assigned treatment, and they are not a statistical comparison of safety between groups. The record does not report an adjusted estimate, uncertainty interval, or test for these summaries. It also does not describe the precise rules used to classify or attribute events.

The registry lists serious-event terms and percentages: Infection, 1.2%; Abdominal injury, 1.0%; Venous thromboembolism (VTE), 0.6%; Nonunion, 0.4%; Manipulation under anesthesia, 0.4%; and Amputation, 0.4%. The denominator and group-specific context for these listed percentages are not reported in the registry record. They should therefore be read as listed event summaries, not as treatment-specific risks or comparative effects.

Safety counts address a different question from the primary efficacy endpoint. The number of participants affected by a serious adverse event is not interchangeable with the count of clinically significant deep SSI, and the registry does not report that these categories are equivalent. The entries offer limited descriptive information but do not support a causal or comparative safety conclusion.

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

The trial record identifies a clinically focused question: whether applying local vancomycin powder before wound closure changes deep SSI outcomes after operative treatment of fractures at high risk of infection. It documents randomization, a parallel-group comparison, the intervention and comparator, and a 26-week primary outcome window. Those details help define what the study was designed to assess.

What the posted record does not provide is the primary-outcome comparison. There are no group-specific primary endpoint counts, effect estimate, confidence interval, or p-value listed. As a result, the direction and size of any difference, and the precision with which it was estimated, are not reported in the registry record. The missing analysis cannot be interpreted as showing either no difference or a difference.

The outcome definition also matters. The primary endpoint focuses on clinically significant deep SSI, defined as infection requiring operative treatment. It does not, by itself, summarize every wound characteristic or infection-related outcome. The record separately mentions ASEPSIS wound assessment and lists pathogen type and bacterial susceptibility and antimicrobial resistance as secondary outcomes, but does not report their results.

Safety entries describe serious adverse events and deaths by group, but no comparative analysis is listed. The event-term percentages are not accompanied by denominator or group-specific context in the registry record. These summaries should not be treated as proof that a particular event was caused by the intervention, nor as a substitute for the primary endpoint analysis.

More generally, a randomized design can support a causal comparison when allocation and follow-up are appropriately conducted and analyzed. That general strength does not remove the need for complete outcome reporting, clear definitions of analysis populations, and an account of missing data and statistical methods. Those details are not reported in the registry record.

The appropriate interpretation is therefore limited: the registry describes a completed randomized trial and its intended comparison, but the posted record does not report the primary results needed to say what the trial found about deep SSI. It cannot establish whether the intervention did or did not change the outcome, or how precise any such estimate would be.

13. Why This Trial Matters Statistically

VANCO addresses a consequential methodological challenge in surgical trials: defining an outcome that is clinically meaningful and observing it over a specified postoperative period. The registry defines deep infection by the need for operative treatment and sets follow-up at 26 weeks. It also explains that the observation window was extended to help capture more infections, relative to the CDC criteria period of three months noted in the record.

The randomized, multicenter, parallel-group design is suited in principle to comparing an intervention added at surgery with standard care. The comparator description is important because standard care includes institution-specific approaches to preventing and treating infection. That variation reflects the pragmatic context described in the record, but it also means the details of routine care may differ across institutions; the registry does not report how such variation was handled analytically.

The trial is statistically important to interpret carefully because a clear design description is not the same as a reported result. A primary endpoint can be well specified, yet readers still need event counts, a treatment contrast, and an uncertainty interval to understand the evidence. Here the record lists no analyses and does not reduce the primary outcome's several categories or time points to a single comparison. As a result, the central comparative question remains quantitatively unanswered in the registry record.

The secondary outcomes concerning pathogen type and bacterial susceptibility and antimicrobial resistance broaden the scientific questions beyond infection occurrence. Reporting these outcomes alongside a clearly defined primary analysis could help distinguish whether groups differ in event occurrence, organism patterns, or susceptibility. The registry record does not report results for those outcomes.

This case illustrates a general principle of trial interpretation: design features establish what a study was intended to learn, while transparent analysis and reporting establish what can be learned from its data. The available record is useful for understanding the study question and endpoint, but not for estimating the trial's primary effect.

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 central limitation for interpretation is that the registry record does not report a primary-outcome comparison. It lists no group-specific counts for clinically significant deep SSI, no effect estimate, and no uncertainty interval or test result. The primary outcome is also described as having several categories or time points and is not reduced to one comparison, so the principal contrast is not fully specified in the posted record.

Several design and analysis details that would support appraisal are not reported in the registry record. These include the randomization procedure, allocation concealment, any masking of outcome assessors, the sample-size justification, the statistical analysis plan, interim analyses, analysis populations, and missing-data methods. Their absence from the record does not prove that the trial lacked such procedures, but it limits assessment of how the trial was conducted and analyzed.

The intervention and standard-care descriptions leave room for practice variation. The powder may be combined with normal saline according to clinical practice, while standard care includes institution-specific measures for preventing and treating infection. The registry does not report how the use of these practices varied or whether that variation was incorporated into the analysis.

The outcome window is described as 26 weeks and six months, and the registry notes that it was extended to capture more infections than the CDC criteria period of three months. The record does not provide detail on completeness of follow-up or how infections identified at different times or in multiple categories were handled in the primary analysis.

Safety reporting is also limited: the serious-event summaries are not accompanied by a comparative estimate, uncertainty interval, or detailed attribution method. The registry does not state the denominator or group-specific context for the listed serious-event percentages. These limits mean that the descriptive safety entries should not be read as a full comparative safety analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO) — NCT02227446.
• Registry record last updated 2026-07-06; status last verified 2026-06.
• Results first posted 2021-06-01.
• 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

The registry record describes NCT02227446, the VANCO trial, as a completed phase 3, multicenter randomized controlled trial with a parallel design and no masking. Recorded enrollment is 1036. The study start is listed as 2014-10, with primary completion at 2018-06.

The trial compares local vancomycin powder placed in the wound bed before closure with standard care that excludes local vancomycin powder. The primary outcome is clinically significant deep SSI during the first 26 weeks after surgery, with deep infection defined as requiring operative treatment. The record also describes ASEPSIS wound assessment and lists pathogen type and bacterial susceptibility and antimicrobial resistance as secondary outcomes.

The registry lists serious adverse-event summaries, but no primary-outcome analysis. It does not report a treatment-effect estimate, confidence interval, or primary-outcome test result. The record therefore describes the intended design and outcomes but does not provide the comparative result needed to quantify the main trial question.