Pregabalin for Central Sensitization in TKA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pregabalin for Central Sensitization in TKA (NCT05460871), a randomized phase 4 study. The primary outcome is Calculate the Change Using the Knee Osteoarthritis Outcome Survey- Activities of Daily Living Subscale.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group, open-label phase 4 study sponsored by the University of Iowa. Allocation was planned at 1:1 between usual care and pregabalin. Masking is listed as none, meaning the record does not describe the treatment assignment as concealed from participants or study personnel. The listed enrollment is 20, and the study status is terminated. The record lists a start date of 2023-02-21 and a primary completion date of 2024-01-25. It does not report why the study was terminated.

The planned study population was patients indicated for TKA with central sensitization who met the inclusion criteria. The brief description says screening included KOOS, a pain score on a scale from 0 to 10, and the CSI. Participants who met criteria and agreed to take part were to provide informed consent before randomization. The record does not report the detailed eligibility criteria or the characteristics of enrolled participants.

The pregabalin group was scheduled to begin medication before surgery and continue through a post-operative dose schedule. Both groups were to receive standard peri-operative pain management and standard physical therapy. The brief description also refers to a pre-operative physical therapy appointment for the pregabalin group, including mobility and function assessments. The record lists planned outcomes beyond the primary KOOS Activities of Daily Living measure, including other KOOS domains, CSI, physical function assessments, and pain after the procedure.

Random allocation can support a fair comparison when outcomes are collected and analyzed as planned, but it does not by itself provide evidence about an effect. In this record, no subjects completed the baseline or follow-up surveys needed for the primary endpoint, and no analyses are listed. The registry record does not report a statistical analysis plan or the reason for termination.

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: After participants signed their informed consent, the participants completed surveys (Columbia Suicide Severity Rating Screen and Central Sensitization Inventory) to determine if they met the study inclusion criteria. Due to the sensitive nature of these surveys, our local IRB required that informed consent be signed before completing the assessments. If suicidal or the participant did not demonstrate Central Sensitization, they were not eligible for continued participation.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: No subjects completed baseline or follow-up surveys.

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 Calculate the Change Using the Knee Osteoarthritis Outcome Survey- Activities of Daily Living Subscale, measured over Approximately 6 weeks.

The primary endpoint is the difference between treatment groups in change on the KOOS Activities of Daily Living subscale. The record describes administration at baseline and at the subject’s follow-up approximately 6 weeks after the procedure. The endpoint therefore concerns change over time within each group and a comparison of that change between groups. It is not simply a follow-up score or a comparison of group averages at a single visit.

KOOS is a patient-reported measure. An Activities of Daily Living subscale is intended to capture how a person reports functioning in daily activities in the context of knee problems. Such outcomes are relevant to a TKA study because they address reported function, rather than relying only on a clinical measurement or an assessment made by study personnel. This is a general description of the role of patient-reported function measures; the registry record does not report a separate rationale for selecting this specific endpoint.

The record describes the survey’s response categories as 1 = none, 2 = mild, 3 = moderate, 4 = severe, and 5 = extreme. It does not state a unit for the primary outcome or report a numerical change, a between-group estimate, or its uncertainty. Most importantly, the population description says no subjects completed baseline or follow-up surveys. Without those measurements, the planned change comparison cannot be estimated from the posted primary-outcome data.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to treatment groups using a chance-based process. In general, this is intended to reduce systematic differences between groups at the start of a study, including differences that might otherwise be related to prognosis. Randomization does not guarantee that groups will be identical, and it cannot compensate for missing outcome measurements. The registry record describes randomized allocation and a 1:1 plan, but it does not report the allocation sequence method or concealment procedures.

What does a parallel-group design mean?

In a parallel-group design, participants are assigned to a group and the groups are compared over the study period. Here the planned groups were usual care and usual care with pregabalin. Because masking is listed as none, the record describes an open-label comparison. In general, lack of masking can matter when outcomes depend on participant reports or assessments that may be influenced by knowledge of treatment assignment. That is a potential design consideration, not evidence that bias occurred in this study.

What is a change-score comparison?

The primary outcome is defined as a difference in change between groups. A change score uses a participant’s measurement at baseline and follow-up to describe how the measurement changed. The group comparison then asks whether the average or otherwise summarized change differs between assigned treatments. The exact summary measure and statistical model are not reported in the registry record. A change analysis requires usable measurements at both time points, unless a prespecified method can handle missing observations. The record reports no completed baseline or follow-up surveys for the primary outcome, so it cannot supply the intended change comparison.

In general, the interpretation of a change-score comparison depends on the scale, the pattern of measurements, and the analysis method. A confidence interval expresses the uncertainty around an estimated effect under the chosen statistical model. A narrower interval indicates greater precision under that model, while a wider interval indicates less precision. No confidence interval or effect estimate is reported for this endpoint, so its magnitude and precision cannot be judged.

What would a significance test tell the reader?

In general, a significance test assesses how compatible the observed data are with a specified null hypothesis under a statistical model. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. Its interpretation also depends on the analysis plan and the data available. The registry record does not report a p-value or a statistical test for the primary outcome. With no completed surveys for that outcome, a test of the planned change comparison is not reported.

The analysis also requires choices about how to summarize the continuous KOOS measure, how to account for baseline values, and how to handle missing observations. These choices can affect estimates and uncertainty. The registry record does not report a statistical analysis plan, model specification, assumptions, or missing-data method. Those items should not be inferred from the endpoint description alone.

How should the planning assumptions be read?

The registry record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. Such calculations are planning illustrations: they depend on their assumptions and are not evidence that an effect was observed precisely or that a study had a particular probability of detecting an effect after the fact. Sample sizes from planning illustrations are not observed power.

No numerical planning results are reported in the registry record described for this study. In addition, the primary outcome has no completed baseline or follow-up surveys, so the posted primary data do not provide an effect estimate to assess. The assumptions can describe how a planning illustration is framed, but they do not replace an outcome analysis or establish the treatment-group difference.

In general, over-dispersion matters when observed variability exceeds what a statistical model assumes; failing to account for it can make uncertainty estimates too small. The registry record does not report count-model analyses or an over-dispersion assessment for this primary continuous outcome, so this is a general statistical point rather than a reported feature of the study. More broadly, statistical methods should be interpreted alongside the actual observations, the analysis population, and the prespecified plan. For this record, those details are not reported sufficiently to reconstruct an analysis, and the primary survey data needed for the planned comparison are absent.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary KOOS Activities of Daily Living change outcome and multiple secondary outcomes, including other KOOS domains, change in CSI, physical function assessments, and pain after the procedure. When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase if each is interpreted without accounting for the family of tests. In general, a multiplicity strategy may define a primary comparison, adjust testing, or treat secondary findings as exploratory. The registry record does not report a multiplicity procedure or a detailed statistical analysis plan.

Missing data are central to interpreting the primary endpoint. The record explicitly states that no subjects completed baseline or follow-up surveys. It does not report imputation, model-based handling of missing observations, or another strategy for producing an estimate despite those missing measurements. Nor does it report whether the same missingness applied to each secondary outcome. The primary endpoint therefore has no reported change estimate to interpret.

The analysis population is also not reported in the registry record. It does not specify how many participants were randomized, received study medication, completed follow-up, or were included in any analysis. Although the listed enrollment is 20, this does not identify the population used for an endpoint analysis, particularly when no analyses are listed. Without those details, readers cannot determine whether any hypothetical analysis would follow randomized assignment, treatment received, or another defined population.

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 adverse-event record lists the control group with 1 at risk, 0 serious adverse events, 0 other adverse events, and 0 deaths. The Study (Pregabalin) group is listed with 2 at risk, 0 serious adverse events, 0 other adverse events, and 0 deaths. No serious adverse event terms are listed.

These figures describe the entries in the registry record; they do not establish that no events occurred outside the recorded follow-up or among participants not represented in the at-risk counts. The record does not explain why the at-risk counts are limited to those shown or how they relate to the listed enrollment. The counts should therefore be read with their recorded denominators, not generalized to all enrolled participants.

In general, an event count of zero in a limited group does not rule out the possibility of events in a larger or differently followed population. A safety comparison also needs suitable exposure and follow-up information, along with uncertainty estimates. Such estimates and fuller details of adverse-event ascertainment are not reported in the registry record. These entries are descriptive and do not establish comparative safety.

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

The posted results do not provide an estimate of the primary outcome. The registry record says no subjects completed the baseline or follow-up surveys required for the KOOS Activities of Daily Living change comparison. As a result, the record cannot show whether the groups differed in reported change, how large any difference might have been, or how precisely it could be estimated.

This is not the same as finding no difference. A finding of no difference would still require data and an analysis capable of estimating the contrast. Nor does the lack of a reported result show that participants had no pain, no functional change, or no adverse effects. Those conclusions are not supported by the primary outcome information.

The study status is terminated, but the reason is not reported in the registry record. It is therefore not possible to attribute the absence of primary surveys to a particular operational or scientific cause. The record also does not report the full analysis plan, the analysis population, or findings for the listed secondary outcomes. These gaps limit what can be concluded from the posted information.

The serious adverse-event entries report zero affected participants in each group among the listed participants at risk, with zero deaths recorded. These observations are limited to the recorded counts and do not establish that pregabalin is safe or unsafe. In general, safety conclusions require appropriate follow-up and a clear understanding of who was observed and for how long; those details are not reported in the registry record.

The appropriate statistical reading is narrow: the registry describes a randomized comparison and a planned patient-reported endpoint, but it does not report the primary outcome measurements or analyses needed to answer the treatment question. Neither benefit nor lack of benefit can be inferred from the missing endpoint data.

13. Why This Trial Matters Statistically

This trial raises a fundamental issue in clinical-trial interpretation: a well-defined research question is not enough to support an answer if the endpoint measurements are unavailable. The planned comparison focused on change in patient-reported daily function after TKA, a kind of outcome that can represent how participants experience everyday activity. But the registry record says no subjects completed the surveys needed for the primary comparison.

The design also illustrates the distinction between allocation and analysis. Randomization can help create comparable groups at the start, but meaningful inference still depends on measuring outcomes, defining the analysis population, and reporting the method used to compare groups. The record describes randomization and open-label treatment, yet it lists no analyses and does not report the statistical analysis plan. Readers therefore cannot assess an estimated effect, its precision, or the handling of missing data.

The listed enrollment of 20 and the small at-risk counts in the adverse-event record also underline why denominators and follow-up context matter. The event counts are not a substitute for a comparative safety analysis, and the listed enrollment cannot be assumed to be the analysis population. Statistical reporting needs to make these distinctions clear.

Finally, the terminated status is informative as a record status but does not explain why the trial ended. Without that context and without endpoint analyses, readers should avoid assigning a cause or interpreting missing results as a treatment finding. The statistical lesson is that transparency about study conduct and missing outcomes is essential to judging what a trial can, and cannot, establish.

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 main trial-specific limitation in the registry record is that no subjects completed baseline or follow-up surveys for the primary outcome. This prevents estimation of the planned difference in KOOS Activities of Daily Living change. The record lists zero analyses, so it does not provide a primary estimate, uncertainty interval, or statistical test.

The study is marked terminated, but the reason is not reported in the registry record. Details needed to understand the study’s conduct are also not reported, including full eligibility criteria, participant characteristics, the number randomized, the number completing treatment, and the analysis population. The listed enrollment alone does not resolve these gaps.

The record describes an open-label design and a patient-reported primary endpoint. In general, awareness of treatment assignment can influence reporting or assessment, so this is a potential source of measurement bias to consider. The registry record does not show whether such influence occurred. It also does not report the statistical analysis plan, the approach to missing data, the multiplicity strategy, or numerical results for the listed secondary outcomes.

Although serious adverse-event counts are recorded, the at-risk counts are limited and the record does not give fuller follow-up or event-ascertainment details. The reason for the limited denominators is not reported. These constraints mean that the safety entries should not be generalized beyond the participants and events represented in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pregabalin for Central Sensitization in TKA — NCT05460871.
• Registry record last updated 2025-03-04; status last verified 2025-02.
• Results first posted 2024-03-18.
• 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

NCT05460871 is a phase 4 randomized, parallel-group, open-label study of pregabalin for patients with central sensitization undergoing TKA. The University of Iowa is listed as sponsor. The record lists enrollment of 20, a start date of 2023-02-21, a primary completion date of 2024-01-25, and a terminated status.

The planned primary outcome was the between-group difference in change on the KOOS Activities of Daily Living subscale, assessed at baseline and approximately 6 weeks after the procedure. The registry record states that no subjects completed baseline or follow-up surveys and lists zero analyses. It does not report a primary outcome estimate or the reason for termination.

The adverse-event entries list zero serious adverse events and zero deaths in each group, with 1 control participant and 2 pregabalin participants recorded as at risk. These counts are descriptive and do not establish comparative safety.