The Influence of Postoperative Analgesia on Systemic Inflammatory Response and POCD After Femoral Fractures Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Influence of Postoperative Analgesia on Systemic Inflammatory Response and POCD After Femoral Fractures Surgery (NCT02848599), a randomized phase 2 study. The primary outcome is Interleukin-6 Concentration in Peripheral Blood..

2. Clinical Question

The clinical question links the method of postoperative pain relief with inflammatory markers and postoperative cognitive dysfunction (POCD). Interleukin-6 is the listed primary endpoint; changes in C-reactive protein, fibrinogen, pain intensity, and postoperative hospital stay are listed as secondary outcomes. These measures address different aspects of the study's stated aims, but the registry record does not report numerical results for them.

The registry record identifies a randomized comparison, but does not report how participants were assigned to the two groups, whether allocation was concealed, or how POCD was defined and assessed. It also does not give outcome values or an analysis comparing the groups. Consequently, the question can be described from the planned comparison, but the size, direction, and precision of any difference cannot be established from the registry record.

3. Trial Design

The registry record describes a phase 2, randomized, parallel-group study with no masking. It lists enrollment of 86 and a completed status. Osijek University Hospital is identified as the sponsor. The recorded study start is 2016-07, and the primary completion date is 2017-07. These registry entries describe the study's design and timeline; they do not establish how many participants completed follow-up or contributed to each endpoint.

The two groups received different postoperative analgesia approaches. In the morphine group, patient-controlled intravenous analgesia is described with a basal flow of 0.5-2 mg / h, a 0.5 mg bolus, a 20-minute lockout interval, and an hourly limit of 3 doses. The description says it would be carried out for 72 hours after surgery. In the levobupivacaine group, continuous epidural local anesthetic is described for 72 hours, using a 0.125% solution, a basal flow of 6 ml / hour, a 2 ml bolus, a 20-minute lockout interval, and an hourly limit of 3 doses.

In a parallel design, each participant is assigned to one group, and the groups are compared. Randomization is intended to support a fair comparison by balancing prognostic factors on average, though the registry record does not describe the randomization sequence or allocation concealment. The record specifies no masking. It does not report whether outcome assessors were masked, so that detail cannot be inferred from the overall masking entry.

The registry record does not report a sample-size justification, planned interim analyses, detailed eligibility criteria, or a full statistical analysis plan. It lists an enrollment of 86, but that figure alone does not explain the assumptions or precision the investigators intended. Safety entries list 35 participants at risk in each group for the displayed event summaries; the relationship between those denominators and overall enrollment is not explained 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.

Before assignment: No patients were excluded from the study before assignment to groups.

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.

Population: The reasons for exclusion of 16 patients were: inability to perform combined spinal-epidural anaesthesia (5 patients), technical problems with PCA pump (4 patients), withdrawal of epidural catheter (2 patients), postoperative delirium and use of antipsychotics (3 patients) and fever and use of antipyretics (2 patients).

6. Primary Endpoint

The registry lists the primary outcome as Interleukin-6 Concentration in Peripheral Blood., measured over Before, 24 and 72 hours after the surgery.

The primary endpoint is interleukin-6 concentration in peripheral blood, measured before surgery and 24 and 72 hours after surgery. The registry record specifies the unit as pg/ml and describes the endpoint using the median and inter-quartile range. It does not report the measured concentrations or a statistical comparison between groups at any of these time points.

Interleukin-6 is an inflammatory mediator. General explanation: Measuring an inflammatory marker at baseline and after surgery can describe how its concentration changes over the perioperative period, while comparing groups can address whether the observed patterns differ between treatment strategies. A baseline measurement can help characterize starting values; later measurements describe values at the stated follow-up times. A marker is not itself a direct measure of every clinical outcome, however. Its interpretation depends on the question being studied and on the evidence connecting the marker with outcomes of interest.

Reporting a median with an inter-quartile range describes the center and spread of observed values without assuming that the data are well represented by a mean and standard deviation. The registry record does not explain why this summary was selected, how repeated measurements were modeled, or how missing measurements were handled. Nor does it provide a threshold for interpreting a change as clinically important. The endpoint definition therefore establishes what was to be measured and when, but not what the measurements showed or how clinically meaningful any difference would be.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

General explanation: Random allocation is used to make treatment groups comparable at the point of assignment, on average, with respect to both measured and unmeasured characteristics. This supports a causal comparison when the assigned groups are analyzed appropriately and follow-up is sufficiently complete. It does not guarantee that the groups will be identical, particularly in a study with limited enrollment. The registry record identifies the study as randomized, but does not describe the sequence-generation method, allocation concealment, or the analysis approach used to preserve the benefits of randomization.

The design is listed as parallel, meaning that the treatment groups are compared over the same study period rather than each participant receiving both approaches in sequence. Masking is listed as none. This can matter when outcomes involve judgment or participant reporting, such as pain intensity or cognitive assessment. The registry record does not say whether outcome assessors were masked, so the masking status of each assessment is not reported in the registry record.

Why report a median and inter-quartile range?

General explanation: The median is the midpoint of ordered observations, and the inter-quartile range describes the spread of the central portion of those observations. These summaries can be useful when measurements are skewed or include unusually high or low values, because the median is less affected by extremes than the mean. Their use does not itself show that the data were skewed, and the registry record does not give a reason for choosing these summaries. It also does not report the actual interleukin-6 distributions.

The endpoint is measured repeatedly in time: before surgery, then 24 and 72 hours after surgery. These observations from one participant are related, not independent replicates. General explanation: An analysis of repeated measurements should account for within-participant dependence; otherwise, uncertainty can be misrepresented. Different valid approaches can target different questions, such as a group difference at a particular time or a difference in patterns over time. The registry record does not state which approach was planned or used. It does not report a model, a test, or separate group estimates at each measurement time.

What do an estimate and its confidence interval convey?

General explanation: A treatment-effect estimate describes the magnitude and direction of a contrast between groups, according to a defined scale and analysis. A confidence interval expresses the precision of that estimate under the assumptions of the statistical method. It helps distinguish an estimate that is precise from one compatible with a wide range of values. A p-value, when reported, addresses compatibility of the data with a specified null hypothesis under the analysis assumptions; it is not a measure of clinical importance. The registry record reports no primary endpoint estimate, confidence interval, or p-value, so these features of the comparison cannot be assessed.

For a median-based endpoint, the exact comparison method matters. A difference between group medians is not interchangeable with a model-based estimate, a rank-based comparison, or a contrast in change over time. These methods can answer different questions and rely on different assumptions. The registry record gives the endpoint summary format but not the contrast definition or method, so a specific estimand should not be inferred.

What do the planning assumptions mean?

The record describes sample-size illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect; the illustrations for time-to-event outcomes would use total events, while other illustrations would use participants per arm. These are planning assumptions, not evidence about the trial's observed power. No numerical sample-size illustration is included in the registry record, and the trial's own sample-size justification is not reported in the registry record.

General explanation: A planning calculation relates a chosen effect size and error criteria to the amount of information a future study may need under a specified model. When a calculation uses an effect estimated from the same study, that estimate may be uncertain. Such illustrations can be useful for planning, but cannot replace the trial's observed estimate and uncertainty. A study's observed result should not be described as having a particular power after the fact.

The normal approximation is an assumption of the stated planning illustration, not a reported description of the outcome analysis. Equal allocation is also an assumption for those calculations; the record does not say that actual allocation was equal. No sample-size numbers are available in the registry record, so no planning requirement or comparison with enrollment can be quantified.

Why can over-dispersion matter?

General explanation: Over-dispersion occurs when observed variability exceeds what a statistical model assumes. If ignored, standard errors may be too small and intervals may appear more precise than warranted. The appropriate response depends on the outcome type and model, and may involve a different variance specification or model. The registry record does not report an analysis model or diagnostics for dispersion; there is no basis to say whether over-dispersion was relevant to this trial.

More generally, statistical methods should be matched to the outcome scale, timing, and data structure. A continuous concentration measured repeatedly, a pain rating, a hospital-stay duration, and an event count need not call for the same analysis. The listed outcomes alone do not identify the chosen methods. Since the record contains no outcome analyses, the methods actually used to estimate treatment effects are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies interleukin-6 concentration as the primary endpoint and names four secondary outcome topics: C-reactive protein, fibrinogen, pain intensity, and postoperative hospital stay. Interleukin-6 is scheduled at three measurement times. Considering several outcomes and time points can raise a multiplicity question: when many comparisons are made, the chance of at least one apparently notable result can increase. General explanation: Researchers may address this by defining a primary contrast in advance, adjusting for multiple comparisons, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy of time-point comparisons, or which comparisons were prespecified for formal inference.

The registry record indicates 0 analyses and gives no outcome estimates, so it is not possible to assess the statistical handling of multiple outcomes or time points. The sample-size assumptions described for planning do not establish how multiplicity was handled in the trial's analysis.

Missing-data methods are not reported in the registry record. There is no accounting of participants with missing measurements, reasons for missingness, or the methods used to include incomplete follow-up. The enrollment figure of 86 does not establish that every participant contributed data at each measurement time or for every secondary outcome. The record also does not specify an intention-to-treat, per-protocol, or other analysis population. These omissions limit assessment of attrition and of whether the analyzed groups retained the balance intended by randomization.

The safety entries list 35 participants at risk in each group, while overall enrollment is 86. The registry record does not explain the relationship between those figures or give a participant flow accounting for enrollment, assignment, follow-up, and analysis. It is therefore not possible to determine from the record whether the safety denominators represent all randomized participants or a subset.

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 non-serious adverse event terms

The registry record lists 0 serious adverse events among 35 participants at risk in the morphine group and 0 among 35 at risk in the levobupivacaine group. Deaths are listed as 0 in both groups. The entries for other adverse events are 5 in the morphine group and 2 in the levobupivacaine group, with 35 participants at risk in each group.

These counts are descriptive. A count of zero means that no event in that category was recorded in the listed group for this summary; it does not prove that an event is impossible or that the treatments have identical safety profiles. The registry record does not report the event terms, severity details for other events, event timing, relatedness to treatment, or the observation period for this summary. It also does not explain the safety denominators in relation to the enrollment of 86.

The displayed counts should not be treated as a complete assessment of comparative safety. A robust interpretation would require clear event definitions, follow-up context, participant accounting, and uncertainty around between-group comparisons. Those details are not reported in the registry record. The figures therefore describe only the adverse-event entries recorded for the listed groups.

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

This trial's registry record establishes that investigators set out to compare two postoperative analgesia approaches in elderly patients after surgical repair of femoral fractures. It identifies interleukin-6 concentration at three times as the primary endpoint and lists additional inflammatory, pain, and recovery outcomes. It also records randomized, unmasked, parallel-group design features and a completed status.

What the record does not establish is whether the groups differed on interleukin-6, pain, inflammatory markers, hospital stay, or POCD. No measured outcome values or comparative effect estimates are reported. Without those results, the direction and size of a difference cannot be described, and its precision or clinical importance cannot be judged. The registry's statement of aims is not evidence that the intended effects occurred.

The adverse-event entries report no serious events or deaths in either group, alongside other-event counts of 5 for morphine and 2 for levobupivacaine. These counts should be read in the context of the listed risk denominators and the missing event details; they do not establish a causal safety difference. The record does not report enough information to characterize those other events or assess how complete their capture was.

Overall, the record is informative about the research question and planned measurement schedule, but limited for evaluating comparative outcomes. A completed trial can still have outcome information absent from its registry record. The absence of reported results should not be interpreted as evidence of no difference, nor as evidence that either approach was superior. A conclusion about treatment effects would require outcome data and analyses that are not reported in the registry record.

13. Why This Trial Matters Statistically

Statistically, the study brings together a randomized comparison, a repeated-measures inflammatory endpoint, and several outcomes that reflect different parts of the investigators' research question. That combination makes clear definitions of the target comparison important. For interleukin-6, a group contrast at a particular time, a comparison of change from baseline, and a comparison of trajectories are not necessarily the same estimand. The registry record identifies measurement times but does not specify which contrast was intended for inference.

The endpoint is summarized using medians and inter-quartile ranges, while the outcomes include measures with potentially different data structures. This highlights why a statistical plan should connect each outcome to an appropriate analysis and describe how repeated observations, missing measurements, and multiple comparisons will be handled. The registry record does not report these details, so readers cannot assess whether the analysis matched the outcome structure or how uncertainty was quantified.

The recorded enrollment and the safety denominators also illustrate the importance of participant accounting. The registry record lists enrollment of 86 and adverse-event risk groups of 35 each, but does not explain how those numbers relate to assignment and follow-up. Clear flow information would help readers understand which participants contributed to each result and whether missing outcome data could affect interpretation.

The trial therefore matters statistically as an example of how a clearly framed randomized question can remain difficult to evaluate when outcome estimates, uncertainty, and analysis details are not reported. Its registry description makes the intended comparison and measurement schedule visible, but does not permit an assessment of the treatment-effect evidence.

14. Limitations

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

The principal limitation for interpretation is that the registry record does not report results for the primary endpoint or the listed secondary outcomes. There are no interleukin-6 values, treatment-effect estimates, confidence intervals, or p-values. Although the record marks the study completed, completion alone does not establish what was observed or how precisely it was estimated.

Several design and analysis details are also not reported in the registry record. These include detailed eligibility criteria, the randomization and concealment procedures, the outcome-assessment approach for POCD, any assessor masking, the planned analysis model, multiplicity handling, missing-data methods, and the analysis population. The record does not describe a sample-size justification or interim analyses. As a result, it is not possible to evaluate the intended power, risk of bias in assessment, or robustness of the planned statistical inference.

The primary endpoint is scheduled at multiple time points, but the registry record does not specify a primary time-point contrast or how repeated measurements were analyzed. It also does not report a threshold for clinical importance. The secondary outcomes span inflammatory markers, pain, and hospital stay, but there are no outcome definitions or analysis details beyond their names.

For safety, the record lists 35 participants at risk in each group, while enrollment is 86, without explaining the participant flow or denominator relationship. Event descriptions and follow-up details are not reported. These limitations mean the recorded adverse-event counts cannot be interpreted as a comprehensive or precise comparison. Overall, the registry record supports description of the study design and recorded safety counts, but not conclusions about efficacy or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Influence of Postoperative Analgesia on Systemic Inflammatory Response and POCD After Femoral Fractures Surgery — NCT02848599.
• Registry record last updated 2020-09-01; status last verified 2020-08.
• Results first posted 2020-09-01.
• 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

NCT02848599 is listed as a completed phase 2 randomized, unmasked, parallel-group study sponsored by Osijek University Hospital. It enrolled 86 participants and compared postoperative epidural levobupivacaine with patient-controlled intravenous morphine after femoral fracture surgery in elderly patients. The primary endpoint was peripheral blood interleukin-6 concentration before surgery and 24 and 72 hours after surgery, summarized by median and inter-quartile range.

The record also lists changes in C-reactive protein, fibrinogen, pain intensity, and postoperative hospital stay as secondary outcomes. It reports no outcome analyses or numerical results for these measures. Safety entries list 0 serious adverse events and 0 deaths in both groups; other-event counts are 5 for morphine and 2 for levobupivacaine, with 35 participants at risk in each group. Further outcome, analysis, participant-flow, and event details are not reported in the registry record.