A Pilot Study Comparing the Safety and Efficacy of Everolimus With Other Medicines in Recipients of ECD/DCD Kidneys: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study Comparing the Safety and Efficacy of Everolimus With Other Medicines in Recipients of ECD/DCD Kidneys (NCT01878786), a randomized phase 2, phase 3 study. The primary outcome is Evaluate Concentration-controlled Everolimus and Low Dose Tacrolimus Compared to MMF/MPA With Standard Dose Tacrolimus at 24 Months.

2. Clinical Question

The composite endpoint includes treated biopsy-proven acute rejection episodes, graft loss, death, and loss to follow-up. The study’s stated purpose was to evaluate these regimens in recipients of ECD/DCD kidneys, which the registry describes as a growing donor fraction and as a setting in which kidney function may be delicate. A secondary objective was to compare renal function at 12 and 24 months post-transplantation.

The registry record lists 25 enrolled participants and says the study was terminated prematurely. It also states that no data analysis was performed on the incomplete data set. Consequently, the clinical question is recorded, but the registry does not provide an analyzed efficacy comparison to answer it. The listed safety counts describe events in the recorded groups; they do not substitute for the primary endpoint analysis.

3. Trial Design

This was a randomized, open-label, parallel-group pilot study listed as Phase 2 and Phase 3. The registry record gives enrollment as 25 and status as terminated. It records a start date of 2013-06 and primary completion in 2017-11. It does not report why the study was terminated or describe the circumstances that led to an incomplete data set.

The regimens differed in both the immunosuppressive medicines and their planned use. One arm received concentration-controlled everolimus with low-dose tacrolimus and corticosteroid withdrawal. A second began with concentration-controlled everolimus and low-dose tacrolimus, then changed to mycophenolate mofetil at Month 3 with corticosteroid. The comparator received standard-dose tacrolimus with mycophenolate mofetil and corticosteroid withdrawal. The record therefore describes regimen-level comparisons, not an isolated comparison of a single medicine while all other treatment remained the same.

Random allocation can, in general, help balance participant characteristics across treatment groups, while an open-label design means treatment assignment is not masked. The registry record does not describe the randomization sequence, allocation concealment, stratification, or procedures used to limit bias in outcome assessment. It also does not provide a statistical analysis plan, target sample-size rationale, or details of recruitment and follow-up by arm.

The primary endpoint was assessed at 24 months post-transplant and was a composite of treated biopsy-proven acute rejection, graft loss, death, or loss to follow-up. Renal function at 12 and 24 months was listed as a secondary outcome. The registry lists three outcome measures but no analyses. Because the study was terminated prematurely and its incomplete data were not analyzed, the record does not support interpreting the randomized design as a completed comparative efficacy trial.

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: Study was terminated prematurely. There was no data analysis performed on the incomplete data set.

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 Evaluate Concentration-controlled Everolimus and Low Dose Tacrolimus Compared to MMF/MPA With Standard Dose Tacrolimus at 24 Months, measured over 24 months.

The primary endpoint is a composite efficacy-failure outcome at 24 months post-transplant. Its listed components are treated biopsy-proven acute rejection episodes, graft loss, death, and loss to follow-up. The endpoint was intended to compare the everolimus-based regimens with mycophenolate mofetil plus standard-dose tacrolimus in de novo recipients of ECD/DCD kidneys.

In general, a composite endpoint combines multiple events into one outcome. It can capture several ways a treatment course may fail and can be useful when each component alone is uncommon. However, a composite estimate does not necessarily tell readers which component drives the result. Components can differ in clinical importance, frequency, and susceptibility to ascertainment. A change in the composite could reflect one component rather than a consistent change across all of them; component-level results are therefore useful for interpretation when available.

Loss to follow-up is included in this endpoint, but the registry record does not explain how it was defined, verified, or handled analytically. It also does not report whether the endpoint was assessed by masked adjudicators or provide component-specific outcome counts. Most importantly, the registry says the study ended prematurely and no analysis was performed on the incomplete data set. Thus, it records the endpoint’s intended meaning, not an estimated treatment effect or a conclusion about the comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance. Its purpose is to reduce systematic differences in baseline characteristics, so that a comparison of outcomes can more plausibly be attributed to assigned regimens rather than to the way participants entered groups. Randomization does not guarantee that groups will be balanced, especially in a pilot study, and it cannot remove bias introduced after assignment by missing outcomes, treatment changes, or differences in follow-up. The registry record identifies the allocation as randomized but does not report the sequence-generation method, concealment procedures, or stratification factors.

Allocation concealment and masking address different sources of bias. Concealment concerns whether upcoming assignments could be anticipated when participants are enrolled. Masking concerns whether participants, clinicians, or outcome assessors know the assigned regimen after allocation. The study is listed as having no masking. The registry record does not report whether any outcome assessment was independently adjudicated or whether safeguards were used for the composite components.

What does an open-label parallel design imply?

In a parallel-group design, participants are assigned to a regimen and followed in that group rather than crossing through every regimen. This makes the comparison depend on outcomes accrued under each assigned strategy. With no masking, knowledge of treatment assignment can potentially affect care, reporting, follow-up, or assessment. These are general considerations, not evidence that such bias occurred in this study. The record does not describe adherence, treatment discontinuation, switching beyond the planned regimen change, or analysis according to assignment.

The regimens are multi-medicine strategies. Their comparison includes differences in tacrolimus dose, everolimus use, the planned change to mycophenolate mofetil in one arm, and corticosteroid use or withdrawal as described in the arm summaries. A result, if analyzed, would therefore pertain to these overall strategies. It would not isolate the effect of everolimus, tacrolimus dose, mycophenolate mofetil, or corticosteroid use individually.

How should a composite endpoint be read?

In general, a composite endpoint treats occurrence of any prespecified component as an outcome. This can make an endpoint more inclusive, but the interpretation depends on its definition and on the component results. A relatively frequent component can dominate the composite even if another component is more severe. Components may also occur at different times or have different relationships to treatment. Component-specific counts and an explicit analysis plan help readers understand what the combined estimate represents. The registry record names the components but does not report definitions beyond those descriptions, component counts, or a method for analyzing the composite.

A time point such as 24 months defines the intended follow-up horizon for the primary comparison. General endpoint analyses might compare the proportion experiencing an event by a specified time, model time until an event, or use another prespecified method. These approaches answer related but not identical questions and rely on different assumptions. The statistical method used for this primary endpoint is not reported in the registry record. It would therefore be inappropriate to infer a risk measure, time-to-event method, or handling of censoring.

What can a confidence interval tell a reader?

In general, a confidence interval expresses the uncertainty around an estimated effect under a specified statistical model and procedure. A narrower interval indicates greater statistical precision than a wider interval, but precision is not the same as absence of bias or clinical importance. A confidence interval can also include values that point in different directions or span effects of different practical importance. The registry record reports no primary efficacy estimate or confidence interval, so none can be interpreted for this study.

Statistical significance is also not a measure of the size or importance of an effect. A p-value, when reported, describes how compatible the observed data are with a specified null model under the assumptions of the test. It does not provide the probability that a treatment works, nor does it make an incomplete analysis informative. No efficacy test or p-value is reported. The record also does not report a prespecified significance threshold or a detailed statistical analysis plan.

Why does over-dispersion matter in general?

General count-data models sometimes assume that variability follows a particular relationship to the mean. Over-dispersion means the observed variation is greater than that model allows. If it is ignored, standard errors can be too small and intervals or tests can appear more certain than warranted. Alternative models or robust variance methods may address this issue, depending on the design and outcome. The registry record does not identify a count-data analysis for the primary endpoint, and no such modeling approach should be attributed to this trial.

More broadly, analysis choices should be prespecified and matched to the outcome structure. A composite outcome with follow-up and possible loss to follow-up requires clear definitions of events, observation time, censoring, and participant inclusion. Those details are not reported. Since the record says the incomplete data set was not analyzed, statistical-method explanations describe general concepts only; they do not describe methods used to produce an efficacy result in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The study lists a primary outcome and a secondary outcome concerning renal function at 12 and 24 months post-transplantation. The registry record lists three outcome measures, but it does not report an analysis of them. It does not explain how multiple endpoints, time points, or treatment comparisons would have been handled statistically. Any multiplicity adjustment, hierarchy of tests, or distinction between confirmatory and exploratory analyses is not reported in the registry record.

Multiplicity matters in general when several outcomes or comparisons are tested: the more opportunities to find an apparently notable result, the greater the chance that a result arises by chance under the relevant null assumptions. Prespecified priorities and appropriate adjustment can help control interpretation. Since no efficacy analysis is reported, there are no trial-specific multiplicity-adjusted or unadjusted results to interpret.

The primary composite includes loss to follow-up as a component, but the registry record does not describe other missing-data patterns, completeness by outcome, reasons for missingness, imputation, censoring, or sensitivity analyses. Nor does it state whether the primary analysis was intended to include participants according to randomized assignment, treatment received, or another analysis population. These analysis populations and missing-data procedures are not reported in the registry record.

The statement that the study was terminated prematurely and that no analysis was performed on the incomplete data set is central to interpretation. It means the registry does not present an efficacy analysis from which to assess missing-data assumptions, multiplicity, or the robustness of a result. It also does not report interim analyses or the reasons for stopping; those matters should not be inferred.

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: sepsis and multiple organ failure (14.3%), er admission for blood transfusion (14.3%), constipation (11.1%), gi surgery (11.1%), left renal mass/nephrectomy (11.1%).

The registry lists serious and other adverse-event counts for the three treatment groups, along with participants at risk and deaths. ERL & TAC: serious adverse events affected 7 of 9 at risk, and other adverse events affected 8 of 9 at risk; deaths were 0. ERL & TAC followed by MMF/MPA: serious adverse events affected 2 of 9 at risk, and other adverse events affected 9 of 9 at risk; deaths were 0. Standard Dose TAC + MMF/MPA: serious adverse events affected 2 of 7 at risk, and other adverse events affected 7 of 7 at risk; deaths were 0.

These are descriptive registry counts, not an adjusted comparison. The record does not provide a statistical test, confidence intervals, exposure-adjusted rates, or a causal assessment. Group sizes and follow-up may differ, and the registry record does not give enough detail to assess those factors. The listed counts therefore should not be treated as proof of a difference between regimens or as evidence that an event was caused by treatment.

The registry also highlights Sepsis and Multiple Organ Failure and ER Admission for Blood Transfusion at 14.3% each, and Constipation, GI Surgery, Left Renal Mass/Nephrectomy, and Neck and Facial Edema at 11.1% each. These terms are reported events, not comparative estimates. The record does not explain selection or attribution for the highlighted terms.

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

The trial record documents a randomized pilot study comparing three immunosuppressive regimens in de novo recipients of ECD/DCD kidneys. It identifies a primary question about composite efficacy failure at 24 months and a secondary question about renal function. It also records safety-event counts by group. These details describe the study’s intended comparison and some recorded events.

They do not establish whether one regimen had fewer composite failures or better renal function. The registry states that the study was terminated prematurely and that no analysis was performed on the incomplete data set. There is no reported efficacy estimate, uncertainty interval, or test result from which to assess the direction, size, or precision of a treatment difference. The absence of an analyzed result is not evidence that the regimens were equivalent, nor is it evidence that one was better.

The safety counts likewise do not establish comparative safety. They are descriptive, and the record does not provide an inferential analysis, adjustment for exposure or follow-up, or causal attribution. The fact that deaths are listed as 0 in each group is a registry entry for this record, not a basis for broad conclusions about the regimens.

In general, a pilot study can help assess feasibility and inform later research, but its interpretation depends on the purpose and methods actually reported. The record does not state a sample-size justification or detailed statistical plan. It is therefore not possible to determine the intended precision, whether the study was designed to test a definitive efficacy hypothesis, or how its incomplete data might have affected estimates. The defensible conclusion is limited: the study posed a comparative question, but its registry record does not report an efficacy analysis that answers it.

13. Why This Trial Matters Statistically

This study is statistically notable because its design and its available results are different things. The registry describes randomization and a parallel comparison, but also says that the trial was terminated prematurely and that the incomplete data set was not analyzed. Consequently, readers can learn what was intended to be compared without obtaining an estimate of comparative efficacy. Keeping design information separate from outcome evidence prevents the existence of randomization from being mistaken for a completed randomized result.

The endpoint also raises a general interpretive issue. Combining treated biopsy-proven acute rejection, graft loss, death, and loss to follow-up may capture multiple forms of efficacy failure, but an overall composite can obscure which component contributes to a result. Component-level reporting and clear endpoint definitions are important to make such a comparison interpretable. The registry record does not provide a component analysis.

The treatment strategies themselves combine several medicines and planned changes in regimen. A completed comparison would address the assigned strategies as a whole, rather than isolate a single medication’s effect. The open-label status is also relevant because awareness of assignment can influence outcome reporting or assessment in general, although the record does not establish that this occurred.

Finally, the safety counts show why descriptive and inferential statements should be kept distinct. Counts and highlighted event terms can inform readers about what was recorded, but without a comparative analysis they do not establish a treatment-related difference. The registry record’s most important statistical contribution is therefore to define the planned question and make clear that no efficacy analysis of the incomplete data was performed.

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 interpreting efficacy is explicit: the study was terminated prematurely, and the registry says no analysis was performed on the incomplete data set. No primary endpoint estimate, confidence interval, or comparative test is reported. The available record therefore cannot quantify or resolve the planned efficacy comparison.

The record does not explain why the trial was terminated, how many participants completed follow-up, how much data were missing, or whether reasons for missingness differed between groups. It does not report the randomization procedure, allocation concealment, adherence, crossovers, or treatment discontinuation. These details would help assess the conduct and interpretability of the planned comparison, but they are not reported in the registry record.

The study is described as a pilot, and enrollment is listed as 25. The registry does not report a sample-size justification or statistical plan, so the intended precision and ability to detect a particular effect cannot be established from the record. No analyzed efficacy result is available to support a retrospective assessment of precision.

The record also gives limited detail about endpoint definitions, component-specific outcomes, outcome adjudication, missing-data handling, and analysis populations. It lists no masking and does not report whether assessors were masked. For safety, group counts and highlighted terms are available, but the record does not provide a comparative statistical analysis, exposure-adjusted rates, or causal attribution. These limitations constrain interpretation of both efficacy and safety and should not be filled in by assumptions about the protocol.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Pilot Study Comparing the Safety and Efficacy of Everolimus With Other Medicines in Recipients of ECD/DCD Kidneys — NCT01878786.
• Registry record last updated 2019-04-26; status last verified 2019-04.
• Results first posted 2019-04-26.
• 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

NCT01878786 is a randomized, open-label, parallel pilot study listed as Phase 2 and Phase 3. It compared concentration-controlled everolimus with low-dose tacrolimus, an everolimus and low-dose tacrolimus regimen followed by mycophenolate mofetil at Month 3, and standard-dose tacrolimus with mycophenolate mofetil. The listed population was de novo renal transplant recipients of ECD/DCD kidneys.

The primary objective was to compare composite efficacy failure at 24 months post-transplant, including treated biopsy-proven acute rejection, graft loss, death, and loss to follow-up. Renal function at 12 and 24 months was a secondary outcome. The registry lists enrollment of 25 and status as terminated; it records the start as 2013-06 and primary completion as 2017-11.

The registry states that the study ended prematurely and no analysis was performed on the incomplete data set. It lists safety counts and event terms, but no efficacy analyses. Thus, the record describes the planned comparison and some safety reporting without providing an analyzed answer to the primary question.