Prophylaxis of Periprosthetic Joint Infections With Calcium Sulfate Beads in Patients With Non-modifiable Risk Factors.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prophylaxis of Periprosthetic Joint Infections With Calcium Sulfate Beads in Patients With Non-modifiable Risk Factors. (NCT03976466), a randomized phase 4 study. The primary outcome is Partipants Achieving a Lower Hip or Knee Periprosthetic Joint Infection Rate With Local Versus Conventional Intravenous Antibiotic Prophilaxys, Measured With CRP, ERS in Serum and Sinovial Fluid Leukocytes , Over the 12-week Observation Period..

2. Clinical Question

3. Trial Design

The registry identifies NCT03976466 as a Phase 4, randomized, single-masked, parallel-group study. Its title concerns prophylaxis of periprosthetic joint infections using calcium sulfate beads in patients with non-modifiable risk factors. The study status is completed, and the registry lists enrollment as 87.

The two interventions are local prophylaxis with antibiotic-loaded calcium sulfate beads and classical parenteral antibiotic prophylaxis. The arm descriptions associate the bead intervention with the Calcium sulfate Group and conventional prophylaxis with the Control Group. Participants were undergoing hip or knee joint replacement. The registry does not specify whether the masking applied to participants, clinicians, outcome assessors, or another group. It also does not describe sequence generation, allocation concealment, or how the randomized assignment was implemented.

The registry lists a start date of 2019-05-22 and a primary completion date of 2020-04-22. The primary outcome timeframe is Day 5 and Weeks 4, 8, and 12. A secondary outcome concerns length of stay as an indicator of hospital economic burden. The study summary also states an aim to examine economic cost, but results for length of stay or cost are not reported in the registry record.

Random allocation is intended, as a general design principle, to make comparison groups similar on average with respect to factors that could affect outcomes. That intention does not establish that the allocation process was concealed or that groups were comparable in this particular trial. The registry record does not report baseline characteristics or enough implementation detail to assess those questions.

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.

Before assignment: Inclusion critera for patients to complete enrolled protocol were: patients over 60 years old, no history of cephalosporine allergy, to have any of the non-modifiable risk factors, patients who accept blood transfusion. Patientes who are institutional entitled.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients who agreed to join the study and who met the selection criteria. After 3 moths presents or not periprosthetic joint infection.

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 Partipants Achieving a Lower Hip or Knee Periprosthetic Joint Infection Rate With Local Versus Conventional Intravenous Antibiotic Prophilaxys, Measured With CRP, ERS in Serum and Sinovial Fluid Leukocytes , Over the 12-week Observation Period., measured over Day 5, Weeks 4, 8, and 12.

The primary outcome is framed as participants achieving a lower hip or knee periprosthetic joint infection rate with local rather than conventional intravenous antibiotic prophylaxis. It is recorded as a count of participants, with assessment on Day 5 and Weeks 4, 8, and 12. The outcome description states that acute periprosthetic infection was determined using CRP and ESR serum biomarkers, described as commonly published biomarkers in the periprosthetic joint infection literature. The stated cut off point for CRP was 93mg/L and for ESR was 44mm/hr.

Synovial-fluid leukocytes are also described as a criterion for defining periprosthetic joint infection, with a cut off point above 12,800 cells/µL. They were included only if serum biomarkers were elevated. This conditional approach means the described assessment does not treat synovial-fluid leukocytes as an independent routine measure for every participant.

Biomarkers are used to operationalize an outcome that may otherwise be difficult to identify consistently. However, the registry description does not fully explain how all results across the assessment times were combined into the participant-level primary outcome, or how a lower rate was calculated between groups. The registry record does not report the number of participants meeting the endpoint, group-specific infection rates, or a comparative estimate. Therefore, the endpoint definition can be described, but the primary result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on linking the trial design, the outcome definition, and the analysis result. In this study, the design is described as randomized, single-masked, and parallel-group. The intervention contrast is local antibiotic prophylaxis with medicated calcium sulfate beads versus classical parenteral prophylaxis. The registry record does not describe the randomization procedure, the party masked, the prespecified statistical analysis, or the numerical primary-outcome analysis. Those omissions limit how specifically the analysis can be evaluated.

What does randomization contribute?

As a general statistical principle, random assignment aims to distribute both measured and unmeasured prognostic factors between study groups without systematic selection. This supports interpretation of a between-group contrast as an estimate of the effect of assignment to the compared strategies, subject to the conduct of the trial and completeness of follow-up. Randomization does not guarantee exact balance in a particular study. The registry does not report the random sequence method, concealment procedures, baseline characteristics, or whether analysis followed randomized assignment.

How should the endpoint be understood?

The primary outcome is a count of participants, and its description uses laboratory criteria to identify acute periprosthetic infection. CRP and ESR are assessed at Day 5 and Weeks 4, 8, and 12, using the stated cut off points of 93mg/L and 44mm/hr. Synovial-fluid leukocytes are included only if serum biomarkers are elevated, with a cut off point above 12,800 cells/µL. This defines a biomarker-based assessment pathway, but the registry record does not fully state how a participant’s repeated assessments become a single primary-outcome classification. It also does not explain precisely how the phrasing achieving a lower rate maps to the reported count outcome.

For a binary participant-level outcome, a typical comparison would summarize how many participants in each group experienced the event and how many did not, then estimate a between-group contrast. General choices include a difference in proportions, a ratio of proportions, or a model-based contrast. These measures answer related but non-identical questions. The registry record does not identify which measure was prespecified or report any primary-outcome counts or estimates, so no particular analysis can be attributed to this trial.

What do uncertainty measures add?

A point estimate alone gives an estimated contrast but not its precision. A confidence interval describes a range of effect values compatible with the data under the method’s assumptions. Its width is influenced by the amount of information and the variability in the observations. A test result addresses compatibility with a specified null hypothesis, but it does not by itself express the magnitude or clinical importance of an effect. These are general statistical concepts; the registry record does not report a primary-outcome estimate, confidence interval, or test result.

For event counts, the amount of information depends in part on how many outcomes occur, not only on the number enrolled. When events are sparse, estimates can be unstable and standard approximations may be unreliable. A zero recorded event count in a safety category does not establish that the true event risk is zero. These general cautions apply to reading rare-event data, but the registry’s zero adverse-event entries should not be mistaken for primary infection outcomes.

What is not available about the analysis?

The registry does not report the statistical plan, sample-size justification, assumptions used for planning, interim analyses, adjustment strategy, or handling of repeated observations. It does not identify analysis populations, such as whether the primary analysis included all randomized participants or only participants with available outcome data. It also does not state how missing biomarker results, withdrawals, or deviations were handled. Those details matter because choices about eligibility for analysis and incomplete follow-up can affect the estimated comparison.

The registry includes a secondary outcome concerning length of stay as an indicator of hospital economic burden. It does not report the analysis method or results for that outcome. The summary additionally mentions economic cost as an aim, but the record does not specify a cost analysis or report cost findings. No conclusions about economic burden can be drawn from the stated objective alone.

Any sample-size illustration based on an observed effect would be a planning exercise, not evidence of the trial’s original design or an observed-power calculation. The registry record does not report the trial’s own sample-size rationale. A planning calculation cannot replace the missing primary-outcome result, and it cannot determine whether the study established a difference. Interpretation must therefore remain limited to the registered design, outcome description, and posted adverse-event entries.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome was assessed at Day 5 and Weeks 4, 8, and 12. Repeated assessment can raise a multiplicity question: if separate comparisons are made at multiple times, the chance of at least one apparently unusual result can increase unless the analysis accounts for the set of comparisons. Alternatively, a prespecified method might combine observations or define a single participant-level outcome across follow-up. The registry record does not say which approach was planned or used, whether one time point was designated as primary, or whether any multiplicity adjustment was applied.

The record lists two outcome measures and two analyses, but it does not provide enough detail to identify their statistical methods or determine how the primary and secondary questions were prioritized. It does not report interim analyses or stopping criteria. These details are not reported in the registry record, so it is not possible to assess how multiplicity was addressed.

Missing-data handling is also not described. The record does not report how many participants had complete biomarker assessment, whether any participants withdrew or missed visits, or how missing serum or synovial-fluid measurements were treated. It does not state whether all randomized participants were included in the primary analysis or whether the analysis used another population. These gaps prevent assessment of possible bias from incomplete follow-up or exclusions.

Repeated observations and missing data are general methodological concerns, not evidence that either occurred or were mishandled in this study. The registry record does not give the information needed to resolve them. The number enrolled and the adverse-event counts do not by themselves establish completeness of primary-outcome follow-up.

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.

The registry adverse-event entries list the Calcium Sulfate Study Group with 44 participants at risk for serious adverse events and zero affected; it lists 44 at risk for other adverse events and zero affected, with zero deaths. For the Control Group, the corresponding entries are 43 at risk for serious adverse events and zero affected; 43 at risk for other adverse events and zero affected, with zero deaths.

These figures describe what is recorded in the adverse-event fields. They should not be read as proof that no adverse events of any kind occurred or that the groups have identical safety profiles. The registry record does not provide event definitions, collection procedures, follow-up completeness, or additional detail on the categories. It also does not report a statistical comparison of safety outcomes. Zero recorded events do not establish zero underlying risk, especially when the amount of information is limited.

Safety entries are distinct from the primary infection outcome. The registry does not report the primary infection counts, so the adverse-event figures cannot answer whether infection rates differed between prophylaxis groups.

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

The registry record describes a completed Phase 4 randomized comparison of local antibiotic prophylaxis using calcium sulfate beads with classical parenteral prophylaxis in hip or knee replacement patients with non-modifiable risk factors. It specifies a biomarker-based approach to infection assessment and the scheduled assessment times. This information clarifies the intended comparison and how infection was to be assessed.

However, the primary outcome results are not reported in the registry record. There is no group-specific count of participants with periprosthetic joint infection, no comparative effect estimate, and no confidence interval or test result. It is therefore not possible to determine from this record whether the observed infection rate was lower in either group, how large any difference was, or how precisely it was estimated. Missing results do not establish equivalence and do not demonstrate absence of an effect.

The biomarker definitions provide an operational framework, but the record does not fully explain how results across the assessment times were combined into the primary participant-level outcome. The registry also does not report baseline characteristics, allocation procedures, analysis populations, missing-data handling, or the prespecified analysis. These omissions constrain assessment of both the validity and the precision of any comparison.

The adverse-event entries show zero recorded serious adverse events, zero other adverse events, and zero deaths in each group. Those entries are not a substitute for a complete safety analysis, and the record does not describe the completeness or detailed methods of safety monitoring. The economic objective and length-of-stay outcome likewise have no reported results. The appropriate interpretation is therefore limited: the registry documents a randomized study and its intended questions, but it does not provide the outcome results needed to judge the primary comparison or economic findings.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it sets out a randomized comparison between two distinct approaches to antibiotic prophylaxis in patients undergoing hip or knee replacement who have non-modifiable risk factors. The question is clinically specific, and the parallel-group design provides a framework for comparing outcomes between assigned strategies. The registry also describes repeated assessment using serum biomarkers and conditional use of synovial-fluid leukocytes.

The outcome definition highlights a general measurement challenge: a clinically important event may be represented through laboratory criteria and observations collected at several times. To interpret a comparative result, readers need to know how those observations combine into a participant-level event and which comparison was planned. The registry gives cut off points and assessment times, but it does not fully describe that aggregation or the statistical strategy.

The record also illustrates why design information and results must be considered separately. Randomization is a useful design feature, but it cannot substitute for group-specific outcome data, an effect estimate, and an account of uncertainty. Without those results, readers cannot assess whether the observed data favor one strategy, whether an estimate is precise, or whether a meaningful difference is compatible with the data.

Finally, the study summary includes an economic aim, and length of stay is listed as a secondary outcome. Reporting those results alongside the primary comparison would be needed to evaluate the stated economic question. The current record identifies that objective but does not report its findings. Thus the trial’s registered design makes the question clear, while the lack of posted outcome results leaves the central statistical interpretation unresolved.

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 registry record does not report the primary-outcome counts or comparative estimate. This is the principal limitation for interpretation: no conclusion about the direction, magnitude, or precision of the infection-rate comparison can be drawn from the record. Although the primary outcome is described as a count of participants and the assessment schedule is stated, the record does not fully explain how repeated measurements were combined into the participant-level classification.

The diagnostic description uses CRP and ESR cut off points and includes synovial-fluid leukocytes only if serum biomarkers are elevated. The record does not report how borderline, discordant, or unavailable biomarker results were handled. It also does not provide further details of the selection criteria or the non-modifiable risk factors represented in the enrolled population. These omissions limit assessment of how the endpoint was applied and to whom the findings would pertain, even if results were available.

Important design and analysis details are not reported in the registry record. These include the randomization procedure, allocation concealment, who was masked, baseline characteristics, sample-size justification, prespecified statistical methods, analysis populations, and missing-data handling. The record does not describe interim analyses or an adjustment for multiple assessment times. These are limits on evaluating the methods; they are not evidence that any particular procedure was absent or incorrectly conducted.

The adverse-event record lists zero events in the stated categories, but it does not describe definitions, monitoring, or completeness of reporting. Results for the secondary length-of-stay outcome and the stated economic objective are also not reported. The completed status alone does not resolve these missing outcome and methods details.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Prophylaxis of Periprosthetic Joint Infections With Calcium Sulfate Beads in Patients With Non-modifiable Risk Factors. — NCT03976466.
• Registry record last updated 2020-08-20; status last verified 2020-08.
• Results first posted 2020-08-18.
• 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

NCT03976466 is listed as a completed Phase 4, randomized, single-masked, parallel-group trial with enrollment of 87. It compares antibiotic-loaded calcium sulfate bead prophylaxis with classical parenteral antibiotic prophylaxis in patients undergoing hip or knee replacement who have non-modifiable risk factors. The registry lists a start date of 2019-05-22 and a primary completion date of 2020-04-22.

The primary outcome concerns participants achieving a lower periprosthetic joint infection rate with local versus conventional prophylaxis. Infection assessment is described using CRP, ESR, and conditional synovial-fluid leukocyte assessment on Day 5 and Weeks 4, 8, and 12. The registry record does not report primary-outcome results or the analysis details needed to interpret a group comparison.

Adverse-event entries show zero serious adverse events, zero other adverse events, and zero deaths in each group. A secondary outcome concerns length of stay as an indicator of hospital economic burden, while the study summary also states an economic-cost aim; neither set of results is reported in the registry record.