Pilot Study of Atorvastatin for Orthopedic Surgery Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study of Atorvastatin for Orthopedic Surgery Patients (NCT02197065), a randomized phase 2 study. The primary outcome is Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP).

2. Clinical Question

The question concerns a laboratory marker of inflammation, not a direct count of heart attacks or other cardiovascular events. The brief summary describes postoperative inflammation and heart injury as the clinical context, and says the investigators hypothesized that atorvastatin would lessen postoperative inflammation. It also explains that a sensitive test of heart injury was planned, including detection of injury without symptoms. The primary result posted in the registry, however, is for hs-CRP; that result should be interpreted as evidence about the stated biomarker endpoint rather than as a direct answer about clinical cardiovascular outcomes.

The study is identified as a randomized phase 2 pilot trial with quadruple masking and a parallel design. Its registry enrollment is 20, while the brief summary describes an intended total of 30 orthopedic surgery patients. The record does not report why those figures differ. The endpoint description states that the change was assessed in 20 randomized participants, with allocation described as 1:1. The question is therefore specific to a small pilot comparison in the participants represented by the posted results; it does not establish how findings would apply to other surgical populations.

3. Trial Design

The POST-OP Pilot Trial is recorded as a randomized, quadruple-masked, parallel phase 2 study. Participants were assigned to atorvastatin or placebo. The registry lists 20 enrolled participants, with 10 in each posted outcome group. The brief summary describes an intended enrollment of 30, but the registry enrollment is 20; the reason for the difference is not reported in the registry record. The listed sponsor is Hospital for Special Surgery, New York.

The atorvastatin arm received 40mg daily. For hip fracture surgery, treatment was to begin at least 4 hours before surgery; for hip or knee arthroplasty, it was to begin 4 days before surgery. The regimen continued until postoperative day 45. The placebo arm is described as a daily sugar pill with the same timing and duration. The registry identifies the intervention entries as atorvastatin and placebo and the posted arms as Atorvastatin and Sugar Pill.

The primary endpoint is the peri-operative rise in hs-CRP, measured as change from preoperative level to postoperative day 2. The registry describes the outcome as a median with an inter-quartile range. It also names peri-operative rise in interleukin-6 (IL-6) levels as a secondary outcome. Three outcome measures and three analyses are listed, but the record does not name all of them in the information available for this analysis.

The registry lists the study as completed. The recorded study start is 2014-09 and primary completion is 2016-07. These dates describe the registry record and do not provide additional information about participant follow-up or the timing of each analysis. A detailed protocol, the rationale for the planned sample size, interim-analysis procedures, and a full statistical analysis plan are not reported 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

Analysis population for the primary outcome, as defined in the registry: 20 orthopedic surgery patients.

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 Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP), measured over Change from preoperative to post-operative day 2.

The primary endpoint is the change in high-sensitivity C-reactive protein (hs-CRP) from the preoperative measurement to postoperative day 2. The registry gives the unit as mg/L and describes the outcome using the median and inter-quartile range. hs-CRP is an inflammation marker; in general, a change endpoint compares a participant’s later measurement with that participant’s starting measurement. The clinical rationale in the registry is that postoperative inflammation is relevant to the study’s interest in cardiovascular complications after orthopedic surgery.

Using a defined postoperative time point makes the comparison specific: the reported endpoint is not a summary of inflammation over the entire 45-day treatment period. Nor is it itself a clinical event such as myocardial ischemia, heart attack, or death. It is a laboratory outcome intended to characterize an aspect of the postoperative response. The brief summary separately describes a sensitive test of heart injury, but the primary posted result is hs-CRP.

The registry reports a median of 98.95 mg/L for the atorvastatin arm and 85.95 mg/L for the sugar-pill arm, with inter-quartile ranges of 63.8 to 151.4 and 52.85 to 124.9, respectively. These are the posted arm summaries for the endpoint. The record’s analysis description refers to a median difference in final values, while the endpoint description refers to change from baseline to postoperative day 2. That distinction matters: an analysis of final values and an analysis of within-person changes are not necessarily the same comparison. The registry does not provide enough detail to resolve that wording difference further.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is summarized with medians and inter-quartile ranges. In general, the median is the middle of an ordered set of observations, while the inter-quartile range describes the interval from the lower quartile to the upper quartile. These summaries are often useful when observations are skewed or when a small number of unusually high or low values could strongly affect a mean. They do not show every participant’s value or the shape of the full distribution.

The registry’s primary endpoint description specifies change from preoperative hs-CRP to postoperative day 2. In general, a change score is calculated by comparing a participant’s follow-up measurement with that participant’s baseline measurement. A group summary of these individual changes answers a different question from a summary of the final measurement alone. The registry’s reported analysis is labelled “Median Difference (Final Values),” so the available wording does not establish whether the test compared changes or final values. The record does not report further details resolving this distinction.

What does the Wilcoxon (Mann-Whitney) test assess?

The reported test is the Wilcoxon rank-sum test, also commonly called the Mann-Whitney test. In general, it compares the ordering of observations between two independent groups. It does not require the same assumptions about normally distributed measurements as a conventional two-sample t-test. The test is often described as a comparison of distributions or relative rankings. It is not automatically a test of the difference between group medians unless additional assumptions about the distributions are reasonable. Because the registry labels its reported estimate as a median difference, that label should be distinguished from the test’s general interpretation.

The posted result gives a p-value of 0.58. In general, a p-value indicates how unusual data at least as incompatible with a null model as the observed data would be if that model and the test assumptions were correct. It does not state the probability that the treatment has no effect, nor does it quantify the probability that a finding will replicate. A threshold for statistical significance and any adjustments to that threshold are not reported in the registry record.

Why does the missing confidence interval matter?

A confidence interval is a range produced by a statistical procedure to express uncertainty around an estimate. In general, a narrower interval indicates greater precision under the method’s assumptions, while a wider interval indicates less precision. The registry reports no confidence limits for the between-group estimate. Therefore, the p-value cannot be paired with an interval showing which effect sizes are compatible with the data under a specified confidence procedure. The arm-level inter-quartile ranges describe spread within each group; they are not a confidence interval for the treatment comparison.

The sample sizes are small, with 10 participants in each arm. In general, small studies tend to provide less precise estimates and have limited ability to distinguish a modest effect from random variation. A non-significant result in a small study should not be interpreted as proof of no effect or equivalence. The registry does not report an equivalence margin or a non-inferiority margin, so neither kind of conclusion is supported by the posted analysis.

What cannot be inferred from the record?

The registry lists three outcome measures and three analyses, and names peri-operative IL-6 rise as a secondary outcome. A full statistical analysis plan, the complete list of outcome definitions, and the strategy for handling multiple outcomes are not reported in the registry record. In general, testing several outcomes can increase the chance of at least one apparently unusual result unless a suitable plan addresses multiplicity. There is not enough information to determine whether any adjustment or hierarchy was used.

Likewise, the record does not describe missing-data handling, exclusions after randomization, the analysis population, or whether the posted analysis followed an intention-to-treat principle. These are distinct features of trial analysis: missing-data methods address unavailable measurements, an analysis population defines who contributes to an estimate, and intention-to-treat generally retains participants in their assigned groups. They cannot be assumed from randomization alone. No interim analyses or stopping rules are reported in the registry record.

General statistical interpretation also depends on design and measurement details. Randomization can support a fair comparison when allocation is implemented and analyzed appropriately, but it does not ensure that every potential source of bias is eliminated. The registry identifies quadruple masking, but does not detail which roles were masked or how masking was maintained. The results therefore describe the posted comparison, while unreported analysis and conduct details remain unknown.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a Wilcoxon (Mann-Whitney) analysis, with a median difference (final values) of 13 and p = 0.58. It does not report confidence limits for that estimate. The primary endpoint description, by contrast, defines the outcome as change from preoperative level to postoperative day 2. Since the analysis label refers to final values, the registry does not make clear whether the sponsor’s test compared final measurements or participant-level changes.

No recalculated result is stated for this comparison in the registry information used for this analysis, so there is no alternate estimate or p-value to set alongside the sponsor’s result. The registry discrepancy indicator is false. Accordingly, the sponsor’s posted analysis remains the reported inferential result; there is no flagged disagreement requiring a recalculated estimate to take precedence. This does not resolve the ambiguity between the endpoint definition and the analysis label.

The posted p-value should be interpreted as a test result, not as a measure of the size, importance, or precision of an effect. Because no confidence interval is reported and the groups each contain 10 participants, the range of effects compatible with the data cannot be assessed from the reported inferential statistics alone.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses. It names peri-operative rise in IL-6 as a secondary outcome, in addition to the primary hs-CRP endpoint. The remaining outcome-measure details are not reported in the registry record. It also does not report whether the outcomes were arranged in a hierarchy, whether the primary analysis was prespecified in a protocol, or whether p-values were adjusted for multiple comparisons.

In general, multiplicity arises when several hypotheses or outcomes are examined. If each is assessed separately, the chance of at least one apparently unusual result can increase. Researchers may address this through prespecified outcome hierarchies, adjusted thresholds, or other methods. Without the analysis plan and complete outcome information, it is not possible to determine whether multiplicity was addressed or how it affects interpretation. The reported p-value of 0.58 is therefore best understood as the result for the stated comparison, rather than as a complete account of every analysis conducted.

The registry does not report the amount or pattern of missing outcome data, the methods used to handle missing measurements, or whether any participants were excluded from the primary analysis. The endpoint description says that 20 orthopedic patients were randomized, and the posted arm summaries each list 10 participants; it does not specify whether all randomized participants contributed a usable endpoint measurement. Missing-data assumptions and sensitivity analyses are not reported in the registry record.

Randomization does not by itself identify the analysis population. The record does not state whether the analysis followed intention-to-treat, a per-protocol approach, or another rule. It also does not describe how deviations from assigned treatment were handled. These omissions matter because an analysis set and its missing-data procedures can affect the meaning of an estimate. The registry record does not report interim analyses, stopping rules, or the statistical plan used to make decisions during the trial. These details should be treated as unknown, not inferred from the phase, masking, or pilot designation.

12. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: deep vein thrombosis (10.0%), hypertension (10.0%), bacteremia (10.0%), delirium (10.0%), alcohol withdrawal (10.0%).

The registry reports serious adverse events in the atorvastatin group among 10 participants at risk, with 1 affected, and in the sugar-pill group among 10 participants at risk, with 2 affected. It reports 0 deaths in each group. These figures describe the posted serious-adverse-event counts for this trial; they do not establish that an event was caused by the assigned treatment.

The record also lists other adverse events among 10 participants at risk in each arm: 3 affected in the atorvastatin group and 5 in the sugar-pill group. The record’s listed serious-event terms include deep vein thrombosis, hypertension, bacteremia, delirium, alcohol withdrawal, and fluid overload, each accompanied by a reported 10.0% figure. The available information does not provide enough detail to attribute those terms to a particular group or determine whether they overlap with the group-level affected counts.

In general, safety counts in a small trial are descriptive and can be unstable. A lack of reported deaths does not establish the absence of risk, and a difference in event counts does not prove a treatment-related difference. The registry does not report detailed event timing, severity beyond the serious classification, causality assessments, or a statistical comparison of adverse events. These counts should therefore be read as a record of reported events in the trial, not as a definitive comparative safety estimate.

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

The result describes a small randomized comparison of atorvastatin and placebo for the stated peri-operative hs-CRP endpoint. The registry reports arm medians of 98.95 mg/L and 85.95 mg/L, inter-quartile ranges for each arm, and a Wilcoxon (Mann-Whitney) test with a median difference (final values) of 13 and p = 0.58. Those figures are evidence about the posted biomarker comparison in this trial, not a direct measure of cardiovascular benefit or harm.

The result does not establish that the treatments are equivalent. Equivalence requires an explicit margin and an analysis designed to assess whether the difference lies within that margin; neither is reported in the registry record. Nor does the p-value establish that there is no effect. With 10 participants in each arm and no confidence interval for the comparison, the precision of the reported estimate is not well characterized by the registry’s inferential statistics.

The result also does not establish whether atorvastatin changes the risk of heart injury, myocardial ischemia, heart attack, or death after orthopedic surgery. Those topics appear in the study background, but the primary result discussed is hs-CRP. A biomarker can be relevant to a clinical hypothesis without serving as a substitute for clinical outcomes. The record’s description of a sensitive heart-injury test does not provide a posted result for that test in the information.

The endpoint wording needs care: it is defined as change from preoperative measurement to postoperative day 2, while the reported analysis is labelled a median difference in final values. The record does not clarify this distinction. The safest conclusion is therefore limited to the reported summaries and the sponsor’s stated test, without assigning a more specific interpretation to the estimate than the registry supports.

As a pilot study, the trial contributes a small set of randomized observations relevant to the planned question. The registry does not report a sample-size justification, an important-effect threshold, or a full statistical plan. The findings should consequently be treated as uncertain and specific to the posted study data, rather than as a conclusive answer about treatment effects in orthopedic surgery patients generally.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary endpoint and analysis label do not align perfectly in their wording. The endpoint is described as a change from baseline to postoperative day 2, whereas the reported comparison is labelled as a median difference in final values. A reader needs to recognize that a comparison of changes and a comparison of final measurements are not necessarily the same estimand. The registry does not provide enough detail to resolve the difference, so interpretation should preserve that uncertainty rather than silently choosing one description.

The study also illustrates why a p-value is not a complete summary of evidence. The reported value, 0.58, is accompanied by no confidence interval. The group summaries convey the observed distributions’ central locations and middle-half spread, but do not show the precision of the between-group estimate. With 10 participants in each group, the limited sample makes precision especially important to consider.

A pilot trial can be useful for examining feasibility and generating information, but the registry does not state a sample-size justification or a target effect for the primary endpoint. Thus, the enrollment should not be interpreted as evidence that the study was designed to rule out clinically meaningful differences. The brief summary describes an intended 30 participants, while the registry records 20 enrolled; the reason for the difference is not reported.

Finally, the record distinguishes a biomarker question from a clinical-outcome question. hs-CRP is the primary endpoint, while heart injury and cardiovascular complications provide the study’s motivation. Keeping those questions separate prevents a laboratory result from being overread as evidence about patient-important events. Together, these features make the trial a useful example of careful endpoint definition, uncertainty, and restraint in interpreting a small randomized comparison.

15. 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 leaves several trial-specific uncertainties. It reports 20 enrolled participants, while the brief summary describes an intended total of 30. The reason for the difference is not reported in the registry record. Although the posted primary endpoint groups each contain 10 participants, the record does not clarify whether every randomized participant had an observed outcome or whether any measurements were excluded.

The endpoint description and analysis label differ: the former refers to change from preoperative level to postoperative day 2, while the latter refers to a median difference in final values. The record does not explain how the test was applied or whether it used participant-level changes. No confidence interval is reported for the primary comparison, and no clinical threshold for an important change in hs-CRP is reported.

The registry does not report a sample-size justification, detailed statistical analysis plan, missing-data methods, analysis population, or procedures for multiplicity. It lists three outcome measures and three analyses, but the available record does not give a complete account of their definitions or how they were prioritized. Interim analyses and stopping rules are also not reported.

The brief summary identifies hip fracture, hip arthroplasty, and knee arthroplasty patients as the intended population, but the posted results do not give a breakdown by procedure. The registry identifies quadruple masking but does not specify which roles were masked or provide details about masking procedures. It also does not provide detailed outcome results for heart injury or cardiovascular events in the information. These omissions limit assessment of the study’s conduct, the generalizability of its biomarker finding, and the relationship between that finding and the clinical questions motivating the trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study of Atorvastatin for Orthopedic Surgery Patients — NCT02197065.
• Registry record last updated 2017-07-02; status last verified 2017-04.
• Results first posted 2017-07-02.
• 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.

19. Record Summary

NCT02197065 is the completed, randomized, quadruple-masked, parallel phase 2 POST-OP Pilot Trial, sponsored by Hospital for Special Surgery, New York. The registry records 20 participants enrolled and lists atorvastatin 40mg daily versus a daily sugar-pill placebo, with treatment continuing until postoperative day 45.

The primary endpoint is the peri-operative rise in hs-CRP, defined as change from preoperative measurement to postoperative day 2. The posted group summaries are medians with inter-quartile ranges. The reported Wilcoxon (Mann-Whitney) comparison gives a median difference (final values) of 13 and p = 0.58, with no confidence interval reported.

The record also names peri-operative IL-6 rise as a secondary outcome. It does not report a full statistical analysis plan, sample-size justification, missing-data procedures, or analysis population. The primary endpoint wording and reported analysis label are not fully aligned, so interpretation should remain close to what the registry states.