Conversion to Everolimus From Calcineurin Inhibitor With Mycophenolic Acid: Impact on Long Term Renal Function in Liver Transplantation.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Conversion to Everolimus From Calcineurin Inhibitor With Mycophenolic Acid: Impact on Long Term Renal Function in Liver Transplantation. (NCT01936519), a randomized na study. The primary outcome is Renal Function as Measured by 24 Hour Urine Creatinine Clearance.

2. Clinical Question

The clinical question concerns a change in immunosuppression strategy and a continuous measure of renal function. The study description frames conversion at 3 months post transplant as a strategy intended to examine renal sparing. That statement describes the motivation for the study, not a conclusion about the observed effects. Numerical outcome results, between-arm comparisons, and uncertainty estimates for the primary measure are not reported in the registry record, so the direction, size, and precision of any difference cannot be assessed from the record.

3. Trial Design

The registry describes a randomized, prospective, parallel-group trial with no masking. Enrollment was 24. The trial is listed as completed, and its phase is listed as NA. Milton S. Hershey Medical Center is named as the sponsor. The study concerns immunosuppression and renal failure in the setting of liver transplantation.

One arm is described as conversion to everolimus combined with mycophenolic acid, with complete discontinuation of the calcineurin inhibitor at 3 months post transplant. The comparator is calcineurin inhibitor immunosuppression with mycophenolic acid. The registry also lists an intervention named Everolimus and a drug intervention named Calcineurin Inhibitor. It does not report the allocation procedure in more detail, the method used to generate a random sequence, or whether allocation was concealed.

The primary outcome is renal function measured by 24-hour urine creatinine clearance, expressed in mL/min. The listed follow-up times are 6 months, 1 year, and 2 years; the outcome description additionally says that an assessment was made at baseline. The registry record does not clarify how the baseline measurement was incorporated into the primary analysis or identify one time point as the sole primary comparison.

Randomization can support a comparison between assigned strategies by reducing systematic differences between groups, but the fact of randomization alone does not establish how well that goal was achieved in a small enrolled sample. With no masking, participants and study personnel would know the assigned strategy; the registry does not report whether outcome assessors were masked. Details of participant flow, adherence, treatment changes, and analysis populations 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

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 Renal Function as Measured by 24 Hour Urine Creatinine Clearance, measured over 6 months, 1 year, and 2 years.

The primary endpoint is renal function measured using creatinine clearance from a 24-hour urine collection. The result is expressed in mL/min, and the registry identifies the summary measure as a mean with standard deviation. Measurements are described at baseline and at 6 months, 1 year, and 2 years post transplant. The primary timeframe is listed as 6 months, 1 year, and 2 years.

As a general statistical and clinical concept, a continuous measure retains information about the range of observed values rather than reducing participants to categories. A mean describes the center of a group’s measurements, while a standard deviation describes their spread. Creatinine clearance is used as a quantitative indicator of renal function; repeated measurements can describe how the measure changes over follow-up. A comparison could therefore concern the values at particular times, change from baseline, or a pattern across time. The registry record does not specify which of these contrasts defines the primary analysis.

The outcome description does not report the observed means, standard deviations, group sizes contributing measurements at each time, or an estimated between-group effect. Those numerical results and their uncertainty are not reported in the registry record. The endpoint definition alone explains what was measured, but cannot establish the magnitude or precision of a treatment-group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized as a mean and standard deviation. The endpoint is 24-hour urine creatinine clearance in mL/min, with assessments described at baseline and at 6 months, 1 year, and 2 years after transplant. The registry record does not report the statistical test or model used for the primary analysis. The explanations below are general and clarify the concepts relevant to this type of outcome; they are not claims about the trial’s unreported analysis plan.

What does a mean describe?

For a continuous measure, the mean is the arithmetic center of the observed values. It can provide an accessible summary for comparing groups, but it does not describe every participant’s result. A mean difference between groups, if estimated, would express the contrast in the measurement’s original units. Here, that unit is mL/min. No group means or mean difference are reported in the registry record.

What does a standard deviation describe?

The standard deviation describes how dispersed individual measurements are around their group mean. It is not the same as the uncertainty in the estimated mean. A standard deviation reflects variation among observations, while a standard error or confidence interval concerns precision of an estimate. Those summaries answer different questions and should not be interchanged. The registry identifies standard deviation as the intended dispersion measure, but does not report its values for the primary endpoint.

Why does the time structure matter?

Measurements at several follow-up times can be analyzed in different ways. An analysis might compare groups at a particular time, compare change from baseline, or model the pattern of repeated measurements. These approaches can target different estimands and may use different assumptions about correlations among measurements from the same participant. The record lists multiple time points but does not specify the primary contrast, the model, or how within-participant correlation was handled. It is therefore not appropriate to attribute a particular repeated-measures method to this trial.

General explanation: when the scientific question concerns change over time, baseline values and follow-up values can both matter. A change score is not identical to a comparison of follow-up values adjusted for baseline. Which approach is preferable depends on the prespecified question, design, and analysis assumptions. The registry record does not report whether baseline adjustment was used or whether change scores were analyzed.

How should uncertainty be considered?

A confidence interval combines the estimated effect with its sampling uncertainty under an analysis model. A narrower interval generally represents greater precision than a wider interval, but interpretation also depends on the range of effects that would matter scientifically. A p-value, if reported, quantifies how unusual data at least as incompatible with a null hypothesis would be under that hypothesis and the model assumptions. It does not give the probability that the null hypothesis is true, and it does not measure effect size. Neither confidence intervals nor p-values for the primary outcome are reported in the registry record.

What can the planning illustrations tell readers?

General explanation: sample-size calculations use assumptions about the effect to detect, variability, significance level, allocation, and analysis method. The planning assumptions described for the illustrations use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. Such illustrations are planning exercises, not observed trial results and not observed power. They should not be treated as the trial’s original design justification. The registry does not report a sample-size justification from the trial’s own protocol, and the numerical illustration results are not reported in the registry record.

General explanation: an illustration based on the observed effect is especially dependent on that estimated effect. If an effect estimate is imprecise, a calculation built from it may also be unstable. It can help explore how planning changes under different assumed effects, but cannot establish what the study was designed to detect or what its actual probability of detecting an effect was. No such probability should be inferred from an illustration.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when data vary more than a statistical model assumes. A model that understates variability can produce uncertainty estimates that are too small, while a model that accommodates extra variation may yield more realistic uncertainty. This concept is especially relevant to outcomes modeled as counts or rates; the primary outcome in this trial is continuous. The registry record does not report an over-dispersion assessment or identify a model for the primary outcome, so no claim can be made about whether it was relevant to the trial’s analysis.

Overall, the registry provides the outcome definition, summary type, units, and assessment schedule, but not the analysis method or numerical primary results. The statistical concepts above describe ways such data can be analyzed and interpreted in general. They should not be mistaken for a report of the method used in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is described at multiple post-transplant time points, with baseline also included in the measurement description. Multiple outcome measures and analyses are listed in the registry record. When several outcomes, time points, or contrasts are tested, the chance of at least one apparently unusual result can increase if the tests are treated as independent opportunities for significance. General approaches to multiplicity include prespecifying a primary contrast, adjusting inference across a family of tests, or clearly labeling additional analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among time points, or which analyses were primary versus secondary.

The record does not report how missing primary outcome measurements were handled, how many participants contributed data at each time, or the reasons for any missingness. General explanation: complete-case analysis uses participants with the required observed measurements, while other methods may use available repeated measurements or make assumptions about the missing-data process. Different methods can produce different estimates, particularly if missingness is related to outcomes or treatment. No method should be attributed to this trial without a report in the registry record.

Analysis populations are also not described. The record does not state whether the primary analysis followed randomized assignment regardless of treatment received, included only participants who adhered to the assigned strategy, or used another population definition. Nor does it describe protocol deviations or treatment discontinuations. Without those details, the population underlying any primary estimate cannot be identified from the registry record.

The registry does not report an interim-analysis plan or stopping rules. This absence of reporting does not establish whether such procedures were or were not used; their status is not reported in the registry record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hepatic artery thrombosis (8.3%).

The registry reports serious adverse events and deaths by arm. In the calcineurin inhibitor and mycophenolic acid arm, 12 participants were at risk and 0 were affected by serious adverse events; 12 were at risk for other adverse events and 12 were affected. In the everolimus and mycophenolic acid arm, 12 participants were at risk and 1 was affected by a serious adverse event; 12 were at risk for other adverse events and 12 were affected. Deaths are reported as 0 in each arm.

The registry lists Hepatic Artery Thrombosis at 8.3% among the top serious-event terms. The record does not specify the arm associated with this term in the listed information, nor does it provide further detail about timing, severity, or relatedness. The term should therefore be read as a reported safety listing, not as evidence that the event was caused by either treatment.

General explanation: adverse-event counts describe events or participants classified under the registry’s reporting definitions; they do not by themselves establish a treatment effect or causal relationship. Small group sizes also make simple numerical comparisons imprecise. The registry record does not provide a comparative safety analysis, event-level details, or a formal assessment of uncertainty. The reported figures describe what was recorded, not the full safety profile or a causal conclusion.

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

The trial addresses an important statistical question: whether renal function, measured by 24-hour urine creatinine clearance, differs over follow-up between two maintenance immunosuppression strategies after liver transplantation. It uses randomized allocation and includes a continued calcineurin inhibitor arm and a conversion-to-everolimus arm, both with mycophenolic acid. These design features define the comparison, but they do not by themselves reveal its result.

The registry record does not report numerical results for the primary outcome. Consequently, it is not possible to state whether the observed mean creatinine clearance was higher or lower in either arm, whether values changed over time, or how large or precise any difference was. The outcome description and the study’s renal-sparing rationale do not establish that the conversion strategy produced a renal benefit. No treatment-effect conclusion can be drawn from the information reported.

Even with numerical results, interpretation would require attention to uncertainty, the number of participants contributing measurements, the handling of repeated observations, missing data, and the exact comparison being estimated. Those analysis details are not reported in the registry record. Clinical interpretation would also require context about how the measure and any observed difference relate to the study population and follow-up; those contextual outcome data are not reported either.

The safety listings provide counts of participants affected by serious and other adverse events and deaths, as well as a serious-event term. These records are descriptive. They do not, without further analysis and event detail, determine whether treatment caused an event or whether event rates differ reliably between strategies.

The appropriate conclusion is therefore bounded: the registry documents the randomized trial’s question, design, endpoint, and limited safety counts, but not the numerical primary findings or sufficient analysis detail to judge the renal-function comparison. The absence of reported results in the registry record should not be interpreted as evidence of no effect, no difference, or no uncertainty.

13. Why This Trial Matters Statistically

This trial is statistically notable for setting up a randomized comparison of two immunosuppression strategies around a clinically relevant continuous measure: 24-hour urine creatinine clearance. The endpoint is recorded in meaningful units, and the follow-up schedule includes several post-transplant assessments. In principle, repeated measurements can help characterize both a group contrast at a given time and the course of the measure over follow-up.

The design also illustrates why specifying the estimand matters. A comparison at one follow-up time, a change from baseline, and an overall trajectory are not interchangeable questions. Each can require a different analysis and can lead to a different interpretation. The registry lists multiple assessment times but does not identify the precise primary contrast or analysis model. That gap limits readers’ ability to connect the endpoint schedule to a specific statistical question.

Enrollment was 24, so precision and the number of observations available at each time are important considerations. The record does not give the observed primary outcome results, confidence intervals, or participant counts for each measurement. Thus readers cannot assess the magnitude or uncertainty of any renal-function estimate. A planning illustration, even when based on an observed effect, is not a replacement for reporting estimates and their uncertainty, and it is not observed power.

The registry’s safety counts offer a further example of the distinction between description and inference. Event counts are useful for reporting what was recorded, but they do not establish causality or quantify a reliable difference between strategies without suitable comparative analysis and detail.

Statistically, the trial matters because its question involves a randomized treatment strategy, a continuous repeated outcome, and multiple time points. Evaluating it well would require transparent reporting of the target comparison, analysis model, missing-data handling, participant flow, and uncertainty. The registry record does not report these elements or the primary numerical results, so the scientific question remains unresolved by the record alone.

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 limitation for statistical interpretation is that the registry record does not report the numerical results for the primary renal-function outcome. Means, standard deviations, between-group estimates, confidence intervals, and p-values are not reported. Without them, neither the direction nor magnitude nor precision of the primary comparison can be assessed.

The outcome is scheduled at multiple times, but the record does not identify the primary contrast or explain how measurements over time were analyzed. It also does not say whether the primary analysis compared follow-up values, changes from baseline, or a repeated-measures pattern. These distinctions affect what an estimate means.

Enrollment is 24, but the record does not report participant flow or the number contributing measurements at each assessment. Reasons for missing data and the method used to handle them are not reported in the registry record. The analysis population, adherence, treatment changes, and protocol deviations are also not described. These omissions prevent assessment of the extent to which analyzed observations represented randomized participants and assigned strategies.

The registry describes the trial as randomized and not masked, but does not report random-sequence generation, allocation concealment, or masking of outcome assessors. It does not provide the statistical analysis plan, sample-size justification, multiplicity approach, interim-analysis procedures, or stopping rules. Their status is not reported in the registry record.

The safety information is limited to summarized counts and a listed serious-event term. The record does not report event timing, relatedness, severity detail, or comparative uncertainty. These limitations mean the safety listings cannot establish causality or support a comprehensive comparison. Overall, the record supports description of the trial’s design and measurements but is insufficient for a full appraisal of its primary statistical findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Conversion to Everolimus From Calcineurin Inhibitor With Mycophenolic Acid: Impact on Long Term Renal Function in Liver Transplantation. — NCT01936519.
• Registry record last updated 2021-01-29; status last verified 2021-01.
• Results first posted 2021-01-12.
• 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

The registry record describes a completed, randomized, prospective, parallel-group trial with no masking and an enrollment of 24. It compares conversion to everolimus with mycophenolic acid, including discontinuation of the calcineurin inhibitor at 3 months post transplant, with continued calcineurin inhibitor and mycophenolic acid.

The primary outcome is renal function measured by 24-hour urine creatinine clearance in mL/min, summarized as a mean with standard deviation. Assessments are described at baseline, 6 months, 1 year, and 2 years post transplant. Numerical results for the primary outcome and details of the analysis are not reported in the registry record.

Safety listings report 0 serious adverse-event-affected participants in the calcineurin inhibitor arm and 1 in the everolimus arm, with 0 deaths in each arm. Other adverse events are reported for 12 participants in each arm. Hepatic Artery Thrombosis is listed among serious-event terms at 8.3%. These figures are descriptive and do not establish causality or a comparative treatment effect.