Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant Recipients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant Recipients (NCT02954198), a randomized na study. The primary outcome is Self-reported Medication Adherence From Baseline to 6 Months..

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. Its status is completed, and the recorded enrollment is 40. The registry lists the study dates as 2016-12-01 for the start and 2018-12-27 for primary completion. Phase is recorded as NA. The sponsor is Medical University of South Carolina.

The treatment schedules share an initial period: tacrolimus immediate-release twice daily, mycophenolate mofetil 1g twice daily, and prednisone for at least 3 months. Following conversion, the comparator regimen is daily tacrolimus, mycophenolate mofetil twice daily, and prednisone for 6 months. The intervention regimen is daily Envarsus, daily everolimus, and prednisone for 6 months. The registry gives target ranges for the tacrolimus-based regimens and the Envarsus and everolimus regimen. It does not report a detailed conversion procedure or the timing of individual assessments beyond the primary outcome timeframe.

Randomized allocation is intended to make treatment groups comparable on average, but randomization does not guarantee that groups will be identical in a trial of this size. With no masking, participants and study personnel knew which regimen was assigned; the registry does not report whether outcome assessment was masked. The record does not describe the randomization sequence, allocation concealment, recruitment approach, or protocol deviations. It also does not report participant baseline characteristics or the number who completed follow-up.

The primary outcome is self-reported medication adherence from baseline to 6 months post conversion. A secondary outcome is the percentage of participants experiencing acute allograft rejection. The record lists 4 outcome measures but does not provide numerical results for the primary outcome or the rejection outcome. The posted adverse-event figures are separate safety summaries and should not be treated as substitutes for results on either outcome.

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 Self-reported Medication Adherence From Baseline to 6 Months., measured over 6 months post conversion.

The primary endpoint is titled “Self-reported Medication Adherence From Baseline to 6 Months.” It concerns the percentage of participants reporting high medication adherence at baseline compared with 6 months after conversion. Adherence was assessed using the Morisky Medication Adherence scale (MMAS), which ranges from 0 to 8. The registry defines a score of 0 as high adherence, 1-2 as medium adherence, and a score greater than or equal to 3 as low adherence.

Self-reported adherence is used to capture participants’ reported medication-taking behavior rather than a clinical event such as rejection. As a general measurement consideration, self-report can provide information about a behavior that may be difficult to observe directly, but it is not the same as an objective measure of medication use. Responses may also depend on recall and reporting. Those general considerations do not establish whether the MMAS accurately captured adherence in this trial.

The registry identifies a baseline-to-follow-up comparison, but does not report the number or percentage classified as highly adherent at either assessment, nor an estimated change or arm contrast. It also does not state how missing questionnaire responses were handled. The endpoint description alone therefore defines what was intended to be measured; it does not indicate the observed adherence result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is registered as randomized and parallel, with no masking. These terms describe the planned structure of the comparison, not the quality or completeness of outcome reporting. Randomization assigns participants to treatment groups by chance; in general, this can reduce systematic differences between groups at baseline. It does not ensure exact balance, and the registry record does not describe the sequence-generation method or allocation concealment. A parallel design means participants are assigned to a regimen and followed in that group rather than switching between assigned groups as part of a crossover comparison. The record does not provide further design details.

What does the primary endpoint measure?

The primary outcome is self-reported medication adherence assessed by the MMAS. The registry specifies a score range of 0 to 8 and classifies 0 as high adherence, 1-2 as medium adherence, and scores greater than or equal to 3 as low adherence. The outcome description focuses on the percentage reporting high adherence at baseline compared with 6 months post conversion. The registry does not state a numerical summary for either time point or explain whether the comparison was intended as a within-group change, a between-group contrast, or both.

As a general statistical point, converting a scale into categories can make results easier to interpret in terms of group proportions, while discarding distinctions between scores within the same category. A comparison of percentages also depends on a clear denominator: readers need to know how many participants were assessed and how missing responses were treated. Those details are not reported for this endpoint in the registry record.

How should estimates and uncertainty be read?

A treatment effect estimate describes the observed contrast on a defined scale. For a percentage endpoint, the scale might be expressed as a difference in proportions, but the registry record does not state such an estimate for this primary outcome. No new contrast can be inferred from the outcome definition or the enrollment figure. The record also gives no confidence interval for adherence.

In general, a confidence interval conveys uncertainty around an estimate. A wider interval indicates less precision, while a narrower interval indicates greater precision, subject to the model and data used. It is not a guarantee that the true value lies in the interval. For a binary or percentage outcome, precision depends in part on the number of participants with observed outcome data and on the distribution of responses. Since the endpoint-specific counts are not reported, the precision of an adherence estimate cannot be evaluated.

A p-value, when reported, measures how unusual the data would be under a specified null hypothesis and model. It is not a measure of effect size, clinical importance, or the probability that a treatment hypothesis is true. The registry record reports no primary-endpoint test result. A lack of a posted p-value should not be interpreted as evidence of no difference.

What do the planning illustrations represent?

The planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. Such illustrations concern hypothetical planning, not the trial’s observed power. Participants per arm for 80% power, when shown for a non-time-to-event outcome, would be a planning quantity rather than a count observed in this trial. The registry record does not report the trial’s own sample-size justification or design assumptions.

In general, a sample-size illustration asks how many participants might be needed under its assumptions to detect a specified effect with a chosen operating characteristic. Its relevance depends on the assumed effect, variability, analysis, and data completeness. It cannot establish that a trial was adequately powered after the fact, and it cannot replace the observed result and its uncertainty. The registry record does not report an interim analysis plan or stopping rules.

What analysis details remain unknown?

The registry record lists no analyses. It does not report a statistical analysis plan, the exact model for the primary endpoint, adjustments for baseline adherence, handling of repeated measurements, or treatment of missing data. It also does not report whether analyses followed randomized assignment or whether participants were analyzed according to treatment received. These unknowns limit assessment of how the primary comparison would have been estimated.

As a general matter, analysis choices should follow the outcome structure and prespecified research question. Repeated measurements may require methods that account for within-participant dependence. Binary outcomes may be analyzed using methods appropriate to proportions, while adjusted analyses can account for specified covariates. These are general methods, not claims about methods used in this trial. Without the analysis plan and numerical results, no such method should be attributed to the registry’s analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures and identifies self-reported medication adherence as the primary outcome. It also lists acute allograft rejection as a secondary outcome. The primary outcome description refers to baseline and 6 months post conversion, and the record marks the outcome as having several categories or time points, so it was not reduced to a single comparison. The registry does not report a multiplicity-adjustment strategy or explain how conclusions across outcomes, categories, or time points were to be controlled.

As a general statistical principle, examining several outcomes or comparisons can increase the chance of at least one apparently unusual result arising by chance. Prespecifying a primary question and an analysis plan can help clarify which comparisons are confirmatory and how other findings should be interpreted. The record identifies a primary outcome, but does not provide enough analysis detail to determine how multiplicity was addressed.

Missing-data procedures are not reported in the registry record. It does not give the number of participants with observed adherence responses at each assessment, reasons for missing responses, or the method used to handle them. In general, missing outcomes can affect both the estimate and its uncertainty, particularly when missingness is related to treatment or participant characteristics. The registry information does not permit evaluation of those possibilities.

The record does not state the analysis populations, including whether results were intended to include all randomized participants or only those with measured outcomes. It also does not report exclusions, withdrawals, protocol deviations, or outcome-specific denominators. These omissions mean that enrollment cannot be assumed to equal the population analyzed for any endpoint.

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: jc virus induced progressive multifocal leukoencephalopathy (5.0%), perinephric fluid collection (5.0%).

The registry lists safety figures by group. For the group titled “Control: Envarsus + MMF,” the serious-event fields report 20 at risk and 1 affected; the other-event fields report 20 at risk and 8 affected; deaths are recorded as 0. For the group titled “Intervention: Envarsus + Everoliumus,” the serious-event fields report 20 at risk and 1 affected; the other-event fields report 20 at risk and 9 affected; deaths are recorded as 0. These are the recorded counts, not comparative effect estimates.

The registry also lists “JC virus induced Progressive Multifocal Leukoencephalopathy” and “Perinephric fluid collection,” each at 5.0%, among the top serious terms. It does not state in this summary how those terms are distributed between groups or explain their denominator. The group labels and event terminology should therefore be retained when interpreting the figures rather than treated as a full account of event timing, severity, or attribution.

In general, event counts describe observed reports and do not by themselves establish whether a regimen caused an event. With limited counts, estimates of between-group differences would be imprecise, and the registry record gives no confidence intervals or statistical comparisons for these safety summaries. The listed other-event counts should not be combined with serious-event counts, since the record does not state whether categories overlap.

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

The registry record describes a randomized comparison of medication regimens after conversion in kidney transplant recipients and identifies self-reported adherence as the primary outcome. It provides the MMAS categories and the intended timeframe, as well as selected safety counts. These details clarify what the study set out to assess and what safety information was posted.

The record does not report the primary adherence percentages, a change from baseline, a between-group estimate, or uncertainty around an estimate. It therefore does not establish whether adherence was higher, lower, or similar between the regimens. The endpoint description and study completion status cannot be used to infer an outcome. No numerical primary result should be reconstructed from the safety figures or from enrollment.

In general, a nonsignificant result, if one were reported, would not by itself demonstrate equivalence or absence of an effect. Equivalence requires a defined margin and an analysis designed to assess whether the estimate is sufficiently precise relative to that margin. The registry record does not report an equivalence objective or such an analysis. Conversely, a difference in an outcome would require examination of its magnitude, uncertainty, and clinical context; none of these can be assessed for adherence from the posted information.

The safety summaries offer counts for serious events, other events, and deaths, but do not provide detailed event-level descriptions, timing, attribution, or inferential comparisons. They should be interpreted as descriptive registry information, not as proof that either regimen is safer. The reported serious-event terms have no stated group distribution in the available summary.

The record also does not report participant characteristics, outcome-specific denominators, missing-data handling, or a statistical analysis plan. These gaps prevent a full assessment of generalizability, potential bias, and precision. The defensible conclusion is limited: the registry documents the design, intended adherence measure, treatment schedules, and selected safety counts, while leaving the primary comparative result unreported.

13. Why This Trial Matters Statistically

This trial raises a statistical question about adherence across regimens that differ after a common initial treatment period. The primary outcome is self-reported and categorized using the MMAS, so interpretation depends on both the scale definition and how responses were summarized. Making those definitions explicit is important: the meaning of a percentage depends on who was assessed and which category was counted.

Randomized allocation provides a framework for comparing assigned regimens, but a design alone does not answer the research question. Readers also need arm-level outcome results, denominators, an effect estimate, and a measure of uncertainty. Those elements are not reported for the primary endpoint in the registry record. This illustrates why registered outcome definitions and posted results must be distinguished: a complete description of what was intended to be measured is not equivalent to a numerical finding.

The outcome spans baseline and 6 months after conversion, while the record notes multiple categories or time points. A clear analysis plan would help readers understand which summary or contrast addresses the primary question and how repeated assessments are handled. The record does not provide that plan. As a general statistical concern, selecting among multiple outcomes or comparisons after seeing data can complicate interpretation, which is why prespecification and transparent reporting matter.

The safety counts also demonstrate the difference between descriptive data and comparative inference. Counts can identify what was recorded, but without a specified comparison and uncertainty estimate they do not show how reliably groups differ. Sparse event data are particularly limited for judging uncommon outcomes. The registry information is useful for identifying the scope of reporting, while its missing comparative results constrain what can be concluded statistically.

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 central limitation for interpretation is that numerical results for the primary adherence endpoint are not reported in the registry record. There are no arm-specific percentages, endpoint-specific denominators, effect estimate, confidence interval, or p-value. As a result, the intended primary comparison cannot be evaluated from the posted information.

The record also does not describe participant characteristics or eligibility criteria in detail. Although the study concerns kidney transplant recipients, the available information does not establish how the enrolled participants compare with other transplant populations. The recorded enrollment is not a substitute for the number analyzed at each assessment, and participant flow or completion by group is not reported.

The primary measure is self-reported, and the registry gives its scoring categories but not questionnaire response rates or missing-data procedures. It does not report whether the assessors were masked; the overall masking entry is none. The analysis plan, randomization method, allocation concealment, protocol deviations, and treatment adherence are also not described in the available record.

The treatment schedules are described, but detailed conversion procedures and information about how medication exposure was maintained are not reported. The registry lists a secondary rejection outcome but gives no numerical rejection result. Selected adverse-event counts and serious terms are available, yet the record does not provide event timing, attribution, group distribution for the listed serious terms, or comparative uncertainty estimates.

Finally, no multiplicity approach, interim analysis plan, or sample-size justification is reported. Planning illustrations based on an observed effect do not supply the missing primary result or establish the trial’s original design rationale. These limitations restrict conclusions about effect size, precision, bias, and applicability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant Recipients — NCT02954198.
• Registry record last updated 2019-12-24; status last verified 2019-12.
• Results first posted 2019-12-24.
• 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

NCT02954198 is a completed randomized, open-label, parallel-group trial sponsored by Medical University of South Carolina, with recorded enrollment of 40. It concerns immunosuppression regimens for kidney transplant recipients. After an initial regimen of tacrolimus immediate-release, mycophenolate mofetil, and prednisone for at least 3 months, the groups converted to daily tacrolimus with mycophenolate mofetil and prednisone, or daily Envarsus with daily everolimus and prednisone, for 6 months.

The primary outcome is self-reported medication adherence at baseline and 6 months post conversion, measured with the MMAS. The registry record gives the scale categories but does not report numerical primary results or an arm-level comparison. It lists acute allograft rejection as a secondary outcome without numerical results in the available record. Safety fields report serious-event, other-event, and death counts for each group, along with selected serious terms. Analysis methods, missing-data handling, outcome-specific denominators, and a multiplicity strategy are not reported.