Comparison of the Cognitive and Motor Effects of Treatment Between an Immediate- and Extended-release Tacrolimus (Envarsus® XR) Based Immunosuppression Regimen in Kidney Transplant Recipients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of the Cognitive and Motor Effects of Treatment Between an Immediate- and Extended-release Tacrolimus (Envarsus® XR) Based Immunosuppression Regimen in Kidney Transplant Recipients (NCT03437577), a randomized phase 1, phase 2 study. The primary outcome is Change in Controlled Oral Word Association Test (COWAT).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group trial with no masking. It lists Phase 1 and Phase 2 and a planned enrollment of 18. Participants were assigned to an immediate-release tacrolimus regimen or an extended-release tacrolimus regimen. The record describes immediate-release tacrolimus as standard of care and the extended-release regimen as replacing standard of care. The sponsor is the University of Minnesota.

The study status is completed. The recorded start date is 2018-05-08, and the primary completion date is 2020-03-31. These dates describe the trial timeline but do not establish when each participant was enrolled, how long each participant was followed, or whether every planned assessment was completed. Those details are not reported in the registry record.

The primary outcome is continuous: change in COWAT score, reported as a mean with standard deviation. The outcome description identifies changes from baseline at 6,12, 24 weeks. The stated outcome population includes all participants who were randomized and participated in outcome-measure data collection. The registry record does not provide arm-specific enrollment or endpoint-analysis counts, so it is not possible to establish how many participants contributed data at each assessment from the listed enrollment alone.

The design information establishes the broad comparison but leaves important operational details unspecified. The randomization method, allocation concealment, treatment adherence, masking of outcome assessors, protocol deviations, and any sample-size justification are not reported in the registry record. No analysis is listed for the outcome, and the registry record does not provide an estimated treatment contrast or its uncertainty. The trial design therefore frames the comparison, while the posted results do not support a quantitative conclusion about the endpoint.

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.

Pre-Randomization

Reasons for not completing this period:

Post-Randomization

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who were randomized and participated in outcome measure data collection are included.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All participants are included at baseline, including those who withdrew participant prior to randomization

6. Primary Endpoint

The registry lists the primary outcome as Change in Controlled Oral Word Association Test (COWAT), measured over Change from baseline at 6,12, 24 weeks.

The primary endpoint is change in the Controlled Oral Word Association Test score. In this test, a participant says words beginning with each of three letters. Each letter is presented for 60 seconds, and the score is the total number of words produced across the three letter trials. The score has a lower bound of zero and no stated upper limit. A higher score indicates greater word retrieval and, according to the registry description, better cognitive function.

The endpoint is intended to capture a specific aspect of verbal fluency: retrieving words in response to a letter cue within a limited period. It does not directly measure every component of cognition, and the registry’s primary endpoint description does not define a motor-function measure. The broader trial objective mentions cognitive and motor effects, but the primary outcome reported in the record is the COWAT change.

Change from baseline is assessed at 6,12, 24 weeks. Comparing change can describe how scores differ from participants’ own baseline measurements over time, while a between-arm comparison would address whether the pattern differed between regimens. The registry record does not report the observed means, standard deviations, or an inferential comparison for any of those time points. The endpoint’s direction is interpretable from its scoring description, but the registry record does not establish whether either arm’s scores changed or whether changes differed between arms.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous endpoint reported as a mean with standard deviation. That choice fits a score measured numerically, and the reported change is defined relative to baseline. General statistical explanation can clarify what such summaries would mean, but the registry record does not report the endpoint summaries or an analysis estimate for this trial.

What does a mean and standard deviation describe?

A mean gives the average score or average change in a group. A standard deviation describes the spread of individual measurements around that average. The mean alone does not show whether participants had similar scores or widely varying scores; the standard deviation adds information about that variability. Neither summary alone describes the uncertainty in a between-arm contrast. For that, an estimate of the contrast and an uncertainty measure such as a confidence interval are needed. The mean and standard deviation for the COWAT endpoint are not reported in the registry record.

What would a between-arm comparison address?

The randomized design is intended to compare the two assigned regimens. A statistical comparison would need to specify what contrast is estimated, such as a difference in mean change at a particular time point or a model-based contrast across follow-up. That is general explanation, not a description of an analysis used in this trial: the registry record lists no analyses and does not report the method used to compare groups. It also does not identify whether the primary inferential target was one time point, a combined time-course estimate, or another contrast.

A confidence interval is a way to express the statistical uncertainty around an estimate. A relatively narrow interval indicates greater precision than a broad interval, under the assumptions of the method. An interval also helps distinguish the estimated magnitude from the uncertainty around it. No confidence interval or treatment-effect estimate is reported for the COWAT outcome, so the precision of the trial’s endpoint comparison cannot be evaluated from the registry record.

Why do the repeated time points matter?

The endpoint is reported as change from baseline at 6,12, 24 weeks. These are repeated assessments of the same participants when data are available. Repeated measurements can be analyzed separately at each time point or with a model that represents the measurements jointly. These approaches answer different questions and make different assumptions. The analysis approach is not reported in the registry record. The record also does not give the number of participants with outcome data at each time point, so the amount of information supporting each assessment cannot be assessed.

When several time points are examined, the analysis plan should clarify which comparison is primary and how other comparisons will be interpreted. If many comparisons are treated as separate opportunities to claim a finding, the chance of at least one apparently unusual result can increase. Methods for addressing this issue include defining a primary time point, adjusting for multiple comparisons, or using a prespecified model. These are general options, not confirmed features of this trial. The registry record does not report a multiplicity strategy.

What does the planning illustration mean?

The sample-size assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such calculations are planning illustrations: they show how sample requirements would depend on assumptions about the target effect and statistical method. They are not the trial’s observed power, do not establish that the study was adequately powered, and should not be mistaken for the original design justification. The original sample-size justification is not reported in the registry record.

The assumptions also do not replace the outcome results. Without the reported observed effect, variability, analysis population, and endpoint counts, a reader cannot use the illustration to judge the precision of the trial’s comparison. The registry record does not report an interim-analysis plan, stopping rule, or other details of the statistical plan. Those details should not be inferred from the fact that the study is marked completed.

Why is variability important?

General statistical principle: greater variability makes it harder to estimate a group contrast precisely when other features are unchanged. If individual COWAT changes vary considerably, a group mean may be an uncertain representation of the underlying average change. The observed standard deviations would be needed to assess this issue for the trial. They are not reported in the registry record.

General statistical principle: over-dispersion occurs when variation is greater than assumed by a statistical model. If a model underestimates variation, its uncertainty estimates may be too small. The registry record does not describe a model for this continuous endpoint or report evidence of over-dispersion; this concept therefore explains a general concern, not a finding about this trial.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is listed at multiple follow-up times: change from baseline at 6,12, 24 weeks. The registry record indicates that the outcome has several categories or time points and was not reduced to one comparison. This leaves the primary inferential comparison unresolved in the posted results. It is not possible to tell whether the intended interpretation focused on one assessment, the trajectory across assessments, or separate comparisons at each time.

Multiplicity is the general statistical issue that arises when several hypotheses or comparisons are considered. If each is assessed independently without a plan for interpreting the set, the chance of finding at least one apparently unusual result can increase. Prespecifying a primary comparison, controlling error across comparisons, or using a model that addresses the repeated measurements are possible approaches in general. The registry record does not report which, if any, approach was planned or used. It also does not report an analysis result for any time point.

Missing-data handling is not reported in the registry record. The stated outcome population includes participants who were randomized and participated in outcome-measure data collection, but that statement does not give counts by arm or time point, explain why data might be unavailable, or describe how unavailable measurements were handled. The record does not say whether an analysis used all available observations, imputation, or another method. These approaches can rely on different assumptions, so the specific method matters when interpreting results.

The analysis population is therefore only partly characterized. The endpoint description gives a general inclusion statement, but actual participant counts and the statistical analysis population are not reported. The record does not report a protocol-deviation approach or an intention-to-treat analysis. It would be inappropriate to assume any of these methods from the randomized design alone.

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.

The registry’s adverse-event record lists the immediate-release tacrolimus group with 3 participants at risk for serious adverse events and 0 affected. The extended-release tacrolimus group lists 5 participants at risk and 0 affected. The record lists 0 deaths in each group. For other, non-serious adverse events, it lists 3 at risk and 0 affected for the immediate-release group, and 5 at risk and 0 affected for the extended-release group. No serious-event terms are listed.

These are the safety counts recorded for the reported groups; they do not establish that no adverse events occurred outside the categories or reporting scope captured in this record. The at-risk counts listed for these safety summaries are not the same as the planned enrollment of 18, and the registry does not explain the difference. The record also does not provide event timing, severity details beyond the serious-event classification, exposure duration, or reasons for the reported denominators.

Zero affected participants in these entries should be read as a registry count, not as proof that an event is impossible or that the regimens have equivalent safety. The small reported at-risk counts also limit what these entries can say about uncommon events. No safety comparison estimate or uncertainty interval is reported in the registry record.

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

The registry record establishes that a randomized comparison was conducted between immediate-release tacrolimus and extended-release tacrolimus in kidney transplant recipients. It names change in COWAT score as the primary outcome, with assessment from baseline at 6,12, 24 weeks. The endpoint is a verbal word-retrieval score, for which higher scores indicate greater word retrieval and better cognitive function according to the registry description.

What the record does not establish is the outcome of that comparison. It does not report group scores, changes, an estimated contrast, a confidence interval, or a statistical test. The registry record therefore does not show whether scores increased or decreased, whether the arms differed, or how precise any difference might have been. Completion status and an endpoint description cannot substitute for those results.

The broader objective includes cognitive and motor function, but the registered primary endpoint described in the record is COWAT change. The record does not provide a motor-function endpoint result. Conclusions about motor outcomes would therefore go beyond the information reported.

In general, a statistically detectable difference and a clinically meaningful difference are distinct questions. Statistical inference concerns how compatible the data are with an assumed model and contrast; clinical meaning requires interpretation of the size and relevance of an effect in context. In this case, neither question can be answered from the registry outcome information because the numerical results are not reported. No conclusion that one regimen is better, worse, equivalent, or ineffective is supported by the posted endpoint data.

The safety entries report zero affected participants for the serious and other adverse-event categories shown, with the listed at-risk counts. Those entries are descriptive registry counts, not a complete characterization of safety or a formal comparison. The appropriate conclusion is limited to what is recorded: the trial design and outcomes are described, while the main cognitive endpoint findings and a quantitative comparison are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary question concerns a continuous cognitive score measured repeatedly after baseline. Such a design requires clear definition of the contrast of interest: a comparison at a particular assessment, a comparison across the time course, or another prespecified summary. The registry record names multiple time points but does not report a single comparison or an analysis method. That distinction affects what an estimate would mean and how readers should interpret its uncertainty.

The record also illustrates why a registered primary outcome and a completed study are not enough to assess the evidence. Interpreting a randomized comparison requires the observed results, the number of participants contributing data, and an account of the analysis. Without those items, neither the estimated effect nor its precision can be evaluated. The planned enrollment of 18 is context, but enrollment alone does not show how much information was available for each outcome assessment.

For readers of clinical research, the endpoint’s measurement properties and direction matter as much as its label. COWAT records word retrieval in response to letter cues, and higher scores are described as better performance. It is a specific measure rather than a general measure of every cognitive or motor function named in the study objective. Distinguishing the registered measure from the broader objective prevents the result from being interpreted more broadly than the endpoint permits.

The record’s planning assumptions also underline a useful distinction between design calculations and observed evidence. A sample-size illustration based on a fraction of an observed effect is not the same as the study’s original justification or observed power. Statistical interpretation depends on the actual estimate, variability, and analysis population, none of which is reported for the primary endpoint. The central statistical lesson is therefore about the limits of inference when outcome reporting is absent, not about which regimen produced a particular result.

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 this trial from the registry record is that the primary endpoint results are not reported. The record gives no COWAT group summaries, standard deviations, treatment-effect estimate, confidence interval, or analysis result. The number of analyses listed is zero. As a result, neither the magnitude nor the precision of the primary comparison can be assessed.

The registered outcome has several time points, but no single comparison is reported. The record does not explain how the repeated assessments were analyzed or how multiplicity was addressed. It does not state whether the outcome was analyzed separately at each time point or through a joint model. Without a stated analysis and results, the role of each time point in the primary inference remains unclear.

The outcome population description says that randomized participants who participated in outcome data collection are included. However, arm-specific and time-specific outcome counts are not reported. The handling of missing data, withdrawals, protocol deviations, and analysis populations is also not reported in the registry record. These omissions prevent assessment of how complete the outcome data were and how the analysis population related to randomization.

The record provides limited design detail beyond randomization, parallel groups, and no masking. The randomization procedure, concealment, assessor masking, regimen details, adherence, and co-interventions are not reported. The original sample-size justification, interim-analysis plan, and statistical analysis plan are also not reported. The sample-size assumptions describe a planning illustration, not verified design features or observed power.

Finally, the safety counts have smaller at-risk denominators than the planned enrollment, and the record does not explain that difference. They provide only a limited descriptive account of the event categories listed. Taken together, these limits mean that the registry record supports a description of the study question and design, but not a full assessment of efficacy, cognitive trajectory, motor effects, or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparison of the Cognitive and Motor Effects of Treatment Between an Immediate- and Extended-release Tacrolimus (Envarsus® XR) Based Immunosuppression Regimen in Kidney Transplant Recipients — NCT03437577.
• Registry record last updated 2021-04-15; status last verified 2021-03.
• Results first posted 2021-04-15.
• 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

NCT03437577 is a completed, randomized, parallel-group trial with no masking, listed as Phase 1 and Phase 2. It planned to enroll 18 kidney transplant recipients and compared immediate-release tacrolimus, described as standard of care, with an extended-release tacrolimus regimen intended to replace standard of care. The recorded start date is 2018-05-08, and the primary completion date is 2020-03-31.

The primary outcome is change in COWAT score from baseline at 6,12, 24 weeks, summarized as a mean with standard deviation. Higher scores indicate greater word retrieval and better cognitive function according to the registry description. The primary outcome results and statistical analysis are not reported in the registry record. Safety entries list 0 serious adverse events and 0 deaths in each group, with the at-risk counts recorded as 3 for immediate-release and 5 for extended-release tacrolimus.