This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Serum Levels of Bupivacaine in Autotransfusion Drains Following Total Joint Arthroplasty (NCT02276040), a registered phase not stated study. The primary outcome is Change in Blood Serum Levels of Bupivocaine From Baseline.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02276040 |
| Phase | Phase not stated |
| Condition | Knee Pain Arthritis |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 26 |
| Arms in the primary outcome | n/a |
| Lead sponsor | OrthoCarolina Research Institute, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People undergoing total joint arthroplasty are the intended population. The record lists knee pain arthritis as the condition and an enrollment of 26. More detailed eligibility criteria and characteristics of the participants are not reported in the registry record.
Intervention
The listed intervention is periarticular bupivicaine and liposomal bupivacaine. The Exparel arm description says participants receive Exparel, identified as periarticular bupivacaine and liposomal bupivacaine.
Comparator
The registry record does not identify a like-for-like control comparison. Allocation is not stated, and the record indicates that this is not a randomized comparison. A control treatment or untreated comparison group is not described.
Primary question
The study asks how bupivacaine levels change from baseline in serum from blood collected in a surgical drain, with measurements planned at 2 and 5 hours post-dose. Its stated hypothesis concerns low or undetectable levels in filtered blood collected by the OrthoPAT® autotransfusion system. Numerical results for the primary endpoint are not reported in the registry record.
These details frame a measurement question rather than an estimate of a treatment contrast. In particular, the record does not describe a comparison that would establish how the measured levels differ from those under another treatment or without the listed intervention. Nor does the endpoint description itself establish whether any measured level is clinically important. The study's hypothesis connects the laboratory measurement with a concern about toxicity risk, but the registry record does not report numerical concentration results or an analysis linking concentrations to clinical outcomes.
3. Trial Design
The registry record identifies NCT02276040 as a completed study, with a start date of 2014-10 and primary completion in 2015-06. Enrollment is listed as 26. The study is classified as other rather than as a randomized comparative trial. Although an Exparel arm is described, allocation is not stated and the record explicitly cautions that the arms are not a like-for-like control comparison.
The intervention description names periarticular bupivicaine and liposomal bupivacaine; the Exparel arm description says participants receive Exparel. The study's stated purpose is to quantify total blood serum levels of bupivacaine in blood collected by the OrthoPAT® autotransfusion system at 2 and 5 hours postoperatively. The primary endpoint description refers to blood collected in a surgical drain after surgery and measurement of change in serum bupivicaine levels from baseline. The registry record does not provide further procedural detail about how these descriptions relate to each other.
The available design information is therefore limited to the intervention, the planned measurement times, and the nonrandomized, non-comparative status. The setting, eligibility criteria, recruitment approach, allocation process, and handling of participants who did not complete measurement are not reported in the registry record. The record also does not report a protocol-based sample-size justification or a detailed statistical analysis plan. Completion status and enrollment describe the study record, but do not establish how many participants contributed usable primary endpoint measurements.
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
| Stage | Exparel |
|---|---|
| STARTED | 26 |
| COMPLETED | 11 |
| NOT COMPLETED | 15 |
Reasons for not completing this period:
| Reason | Exparel |
|---|---|
| Physician Decision | 15 |
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: Patients that completed the study.
| Characteristic | Unit | Exparalel |
|---|---|---|
| Participants analysed | 11 | |
| Age, Continuous | years | 63 (60 to 70) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 7 |
| Region of Enrollment: United States | participants | 11 |
| Surgery Performed: Total Hip Arthroplasty | Participants | 5 |
| Surgery Performed: Total Knee Arthroplasty | Participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Blood Serum Levels of Bupivocaine From Baseline, measured over Change from baseline at 2 and 5 hours post-dose.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | ug/cc |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled change in blood serum levels of bupivocaine from baseline. It concerns bupivacaine levels measured in blood collected in a surgical drain after surgery, with change assessed at 2 and 5 hours post-dose. The stated unit is ug/cc. The summary statistic is the median, and dispersion is described using the inter-quartile range. The registry record does not report numerical endpoint values, the baseline level, the number of observations contributing at either time, or the results of an analysis.
In general, a median describes the central position of observed values without relying on the arithmetic mean. The inter-quartile range describes the spread of the central portion of a distribution. These summaries can be useful when measurements are skewed or include unusually high or low values, although the registry record does not state why these summaries were selected for this study or describe the observed distribution.
Measuring levels in collected blood addresses the study's stated question about bupivacaine in the drain blood. It is a laboratory endpoint, not by itself a clinical outcome or a direct measure of toxicity. The registry record's stated hypothesis gives the measurement a safety rationale, but numerical results and any clinical interpretation of them are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the primary endpoint definition and timing, but not the endpoint results. It therefore does not support a numerical description of the median change, the inter-quartile range, or the difference between baseline and either postoperative measurement. No confidence interval, test statistic, or p-value for this endpoint is reported in the registry record. The record lists no analyses. Consequently, the available information cannot show how precisely the concentration changes were estimated or whether an inferential comparison was conducted.
The study's stated hypothesis is that filtered blood from the OrthoPAT® autotransfusion system contains low or undetectable bupivacaine hydrochloride levels, and that reinfusion of collected blood in conjunction with periarticular bupivacaine injections will not pose a toxicity risk. This is the study rationale, not a reported finding. The registry record does not report measured concentrations with which to evaluate that hypothesis, nor clinical outcome data that would establish a relationship between concentration and toxicity.
The record also does not describe a randomized or like-for-like control comparison. Without a specified comparator and allocation method, a treatment contrast cannot be interpreted as a randomized estimate. The stated endpoint is principally a within-participant change-from-baseline measurement, but the record does not report the values, the analysis population, or whether the same participants contributed measurements at both times. It is therefore not possible to characterize the size, direction, or uncertainty of any change.
The adverse-event summary lists an Exparel group with 11 participants at risk for serious adverse events and 0 affected; it also lists 11 at risk for other adverse events and 0 affected, with 0 deaths. These are the posted counts for that group. They do not fill the gap in the primary endpoint results: event counts and serum concentration measurements answer different questions. Nor do the counts establish that risk is absent, particularly when the registry record does not provide further event definitions, observation details, or uncertainty estimates.
In general, a confidence interval would indicate the range of estimates compatible with the data and analysis under its assumptions. No such interval is reported for the primary outcome. The appropriate interpretation is therefore limited: the registry record describes what the study intended to measure and reports a small set of safety counts, but it does not provide the numerical primary outcome results needed to assess the measured bupivacaine levels.
9. Statistical Methods Explained
The primary endpoint is framed as change from baseline in serum bupivacaine levels, with observations planned at 2 and 5 hours post-dose. A change-from-baseline outcome uses each participant's baseline measurement as a reference for a later measurement. In general, this can help describe within-participant movement over time, but it does not automatically control for changes that would have occurred without the intervention. The registry record does not report the calculation details, the baseline values, or the resulting changes.
What do the median and inter-quartile range describe?
The registry record specifies the median as the summary measure and the inter-quartile range as the measure of dispersion. In general, the median locates the middle of the observed values when they are ordered. The inter-quartile range describes the span of the central portion of those values. Together, these summaries describe central tendency and spread without requiring the mean and standard deviation to represent the data well. They do not, on their own, quantify uncertainty in the estimated median or establish a difference between time points.
The registry record does not provide concentration values, an inter-quartile range, or a distribution plot in its reported outcome information. It also does not state whether any observations were below a detection threshold, how such values would be handled, or what assay procedures and detection limits were used. Those details would matter when interpreting a claim about low or undetectable levels, but they are not reported in the registry record.
How should repeated time points be understood?
The endpoint timeframe includes measurements at 2 and 5 hours post-dose. In general, observations from the same participant at multiple times are related rather than independent. An analysis should account for that relationship if it makes an inferential claim across time. The registry record does not report whether results were analyzed separately at each time, jointly across time, or by another approach. It does not report the number of participants measured at each time or whether paired observations were available.
The planned measurement times alone do not establish that change occurred, that a trend was present, or that any pattern was statistically distinguishable from measurement variability. For such conclusions, numerical estimates and an analysis method would be needed. Neither is reported for this endpoint in the registry record.
What inference is supported by the design?
The record identifies the study as nonrandomized and says the arms are not a like-for-like control comparison. Allocation is not stated. In general, random allocation can support causal comparisons by balancing treatment groups in expectation, while nonrandomized comparisons can be affected by differences between groups. In this record, the lack of a specified comparable control means there is no reported basis for an arm-to-arm treatment effect. A before-and-after measurement can describe change among measured participants, but without reported results it cannot be interpreted quantitatively.
No hypothesis test, confidence interval, regression model, covariate adjustment, or other inferential procedure is reported for the primary endpoint. General statistical interpretation depends on the estimand, the distribution and dependence of observations, the handling of missing measurements, and the assumptions of any model. Those analysis details are not reported in the registry record. The record lists zero analyses, so no inferential result should be inferred from the endpoint description alone.
How should planning calculations be read?
The planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They specify that the effect to detect is a stated fraction of the observed effect. In general, a sample-size calculation estimates the amount of information a planned study would need under assumptions about the effect, variability, allocation, and analysis. It is not evidence that the study achieved a particular probability of detecting an effect.
The assumptions characterize the calculations as planning illustrations, not as the trial's own design. They are not observed power. The registry record does not report the study's sample-size justification or enough numerical primary outcome information to evaluate the illustration's inputs. The description also distinguishes between participants per arm for ordinary outcomes and total events for time-to-event calculations; the primary endpoint is a continuous measurement, not a time-to-event endpoint. No calculated participant targets are stated in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The endpoint is scheduled at 2 and 5 hours post-dose. Considering multiple time points can raise a multiplicity question if separate hypothesis tests are conducted, because repeated testing can increase the chance of at least one apparently notable result. In general, a prespecified analysis can address this by defining a primary time point, using a joint model, or applying an appropriate adjustment. The registry record does not report whether tests were conducted, whether either time point was designated as the principal inferential comparison, or whether multiplicity was addressed.
The record does not report a missing-data plan, the number of missing measurements, reasons for missingness, or an approach to handling incomplete baseline-to-follow-up observations. Those omissions limit assessment of whether the participants contributing data differed from those enrolled. The endpoint population field contains no description, and an analysis population is not reported in the registry record. Enrollment of 26 should therefore not be read as evidence that all participants contributed primary endpoint data.
The registry record also does not report exclusions, deviations from the planned measurement schedule, sensitivity analyses, or a protocol-defined hierarchy of outcomes. It lists one outcome measure and no analyses. These omissions do not establish that the study lacked internal procedures; they mean that the procedures and their consequences are not reported in the registry record. Without an analysis plan and outcome results, the reader cannot assess selective reporting, the effects of missing observations, or the robustness of any primary endpoint estimate.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Exparel | 0 | 11 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Exparel | 0 of 11 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Exparel | 0 of 11 |
The adverse-event summary lists the Exparel group with 11 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 11 participants at risk and 0 affected. Deaths are listed as 0, and no top serious-event terms are listed. These counts describe what the registry record reports for the displayed group; they are not serum concentration results.
In general, an observed count of zero means no events were reported in the stated group and category. It does not prove that the underlying event risk is zero. Interpretation also depends on how events were defined, how long participants were observed, and how completely events were collected. Those details are not reported in the registry record. The enrollment of 26 is not the denominator in the adverse-event summary, which lists 11 at risk in each category.
The counts are descriptive. No comparative safety estimate, confidence interval, or statistical test is reported. They should not be treated as evidence that the intervention cannot be associated with adverse events or as a substitute for the missing primary endpoint measurements.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study was designed to measure bupivacaine levels in collected blood at 2 and 5 hours after dosing, and that its primary endpoint was described as change from baseline. It also reports an Exparel arm and adverse-event counts. These registry entries explain the research question and the type of information the study sought to collect.
What the record does not establish is the amount of bupivacaine measured, the direction or size of any change, or the precision of an estimate. Numerical endpoint results and inferential analyses are not reported. The record therefore cannot support a conclusion about whether levels were low or undetectable, or how measurements at the two postoperative times compared with baseline.
The stated hypothesis connects filtered drain blood and reinfusion with concern about toxicity. A laboratory concentration endpoint can inform that question, but it is not by itself a clinical toxicity outcome. The registry record does not report a concentration threshold, a demonstrated relationship between measured levels and clinical effects, or data establishing that reinfusion did or did not pose a risk. The safety counts are limited to the reported event categories and denominators; they do not answer the concentration question.
Because allocation is not stated and there is no like-for-like control comparison, the record also does not permit a randomized treatment-effect interpretation. The most defensible reading is that this is a completed study with a stated laboratory measurement objective, but the numerical primary endpoint findings needed to evaluate that objective are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates the distinction between a clearly stated measurement question and a reported statistical result. The endpoint identifies the material to be measured, the reference point, the planned times, the unit, and the summary statistics. Those details are important for interpreting an eventual estimate. But without actual values and an analysis, the endpoint description cannot tell readers what was observed or how uncertain an estimate would be.
It also illustrates why design labels matter. A nonrandomized study without a like-for-like control comparison may be useful for describing measurements in its participants, but it does not supply the same basis for a causal contrast as a randomized comparison. The registry record's own caution about the arms prevents an unwarranted treatment-effect interpretation.
Finally, laboratory outcomes and safety counts should be kept distinct. Serum levels address the proposed pharmacologic measurement; adverse-event counts describe reported clinical events. Neither can substitute for the other. Statistical interpretation requires matching each claim to the endpoint, denominator, design, and analysis actually reported. Here, the concentration results and inferential analyses are not reported, so the scientific rationale is clearer than the evidence available for evaluating it.
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 interpreting this study is that numerical primary endpoint results are not reported in the registry record. Although the outcome definition gives the unit, summary statistic, dispersion measure, and planned times, the measured levels, changes from baseline, and counts of observations are unavailable. Precision and distribution cannot be assessed.
The registry record does not describe a like-for-like comparator, and allocation is not stated. This limits the scope of any comparative interpretation. The enrollment is 26, while the adverse-event summary lists 11 at risk in the Exparel group; the registry record does not explain the relationship between these counts or identify the primary endpoint analysis population. It would be inappropriate to assume that enrollment equals the number with complete measurements.
Further details relevant to measurement and analysis—including assay detection limits, treatment of values below detection, missing-data handling, protocol deviations, and the statistical analysis plan—are not reported in the registry record. The record also does not report clinical outcomes linking serum levels to toxicity. These limitations are specific to what is available in the record and do not establish what information may have been collected outside it.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Serum Levels of Bupivacaine in Autotransfusion Drains Following Total Joint Arthroplasty — NCT02276040.
- Registry record last updated 2017-11-30; status last verified 2017-07.
- Results first posted 2017-11-30.
- 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.
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18. Record Summary
NCT02276040 is listed as a completed study with enrollment of 26, a start date of 2014-10, and primary completion in 2015-06. Its stated purpose is to quantify bupivacaine serum levels in blood collected through the OrthoPAT® autotransfusion system after total joint arthroplasty.
The primary endpoint is change from baseline in serum levels at 2 and 5 hours post-dose, summarized by the median and inter-quartile range in ug/cc. Numerical results and analyses are not reported in the registry record. The record describes an Exparel arm but no like-for-like control comparison; allocation is not stated. Its adverse-event summary lists 11 at risk and 0 affected for serious events, 11 at risk and 0 affected for other events, and 0 deaths.