This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Everolimus Monotherapy as Immunosuppression After Liver Transplant (NCT04063865), a randomized phase 3 study. The primary outcome is Long-Term Renal Function With Tacrolimus Monotherapy.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04063865 |
| Phase | Phase 3 |
| Condition | Kidney Failure |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 14 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Indiana University |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns people receiving a liver transplant. Its rationale focuses on recipients described as having near-normal kidney function before transplantation. The registry record does not give further eligibility details in the information, so the population should not be taken to represent every liver-transplant recipient or people with different baseline kidney function.
Intervention
The study arm was everolimus monotherapy as maintenance immunosuppression. The trial rationale proposes using everolimus after induction immunosuppression with rabbit anti-thymocyte globulin, while removing tacrolimus from the maintenance regimen. The record describes this as a proposed strategy; it does not provide the primary renal-function result needed to assess its effect in this trial.
Comparator
The control arm received tacrolimus as maintenance immunosuppression. The trial rationale identifies concern about tacrolimus-associated nephrotoxicity as the reason to study a tacrolimus-free approach. That rationale is not itself evidence of a difference in kidney function between the trial arms.
Primary question
The primary outcome description identifies glomerular filtration rate as the measure of long-term renal function, with assessment planned for 36 months post-transplant. The registry record states that the trial ended before any subject reached that timepoint and that no data were collected for this outcome. The record therefore does not answer whether the maintenance regimens differed on the stated renal-function measure.
3. Trial Design
The registry describes a Phase 3, randomized, parallel-group trial with no masking. It lists an enrollment of 14 and names Indiana University as the sponsor. The record gives a start date of 2019-05-09, a primary completion date of 2020-07-02, and a terminated status. It does not report the reason for termination in the registry record for this analysis.
The comparison was between tacrolimus maintenance immunosuppression in the control arm and everolimus monotherapy maintenance immunosuppression in the study arm. The brief summary describes a rationale in which rabbit anti-thymocyte globulin is used for induction, followed by a tacrolimus-free maintenance approach. The intervention list names tacrolimus and everolimus, but further details of treatment schedules, dosing, adherence, and changes in treatment are not reported in the registry record.
Random assignment is intended to make treatment groups comparable on average, including with respect to factors that are not measured. That benefit depends on how assignment was carried out and on what happened after assignment. The registry record does not report the randomization sequence method, allocation concealment, or procedures for maintaining assigned treatment. With no masking, participants and study personnel were not masked according to the registry entry; whether outcome assessors were masked is not reported in the registry record.
The registry record reports that the trial was terminated before any subject reached the 36-month timepoint for the primary outcome. That circumstance limits what can be learned from the planned long-term comparison. The record does not report the reasons for termination or whether the end of the trial affected collection of other outcomes.
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
| Stage | Control Arm | Study Arm |
|---|---|---|
| STARTED | 6 | 8 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 6 | 8 |
Reasons for not completing this period:
| Reason | Control Arm | Study Arm |
|---|---|---|
| Physician Decision | 1 | 3 |
| Study Closed Prior to Completion | 4 | 4 |
| Withdrawal by Subject | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Study was terminated prior to any subject reaching the 36 Month timepoint. No data were collected for this outcome measure.
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.
| Characteristic | Unit | Control Arm | Study Arm | Total |
|---|---|---|---|---|
| Participants analysed | 6 | 8 | 14 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 | 7 | 13 |
| Age, Categorical: >=65 years | Participants | 0 | 1 | 1 |
| Age, Continuous | Years | 51.33 (48 to 59) | 57.5 (51 to 66) | 54.86 (48 to 61) |
| Sex: Female, Male: Female | Participants | 0 | 4 | 4 |
| Sex: Female, Male: Male | Participants | 6 | 4 | 10 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 6 | 8 | 14 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 6 | 8 | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Long-Term Renal Function With Tacrolimus Monotherapy, measured over 36 months post-transplant.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome description names glomerular filtration rate (GFR) as the measure of renal function, with a timeframe of 36 months post-transplant. GFR is used as an indicator of how well the kidneys filter blood. In general, comparing a measure of renal function between treatment groups can help assess whether their kidney-function profiles differ over time. That general rationale does not establish that a difference occurred in this trial.
The registry’s primary outcome title refers to “Long-Term Renal Function With Tacrolimus Monotherapy,” while the recorded study arm is everolimus monotherapy and the control arm is tacrolimus maintenance immunosuppression. The outcome description itself identifies GFR, but the registry record does not clarify the wording of the title. The stated outcome timeframe is 36 months post-transplant.
Crucially, the registry record says the trial was terminated before any subject reached that timepoint and that no data were collected for this outcome measure. It reports no GFR values, treatment-group estimates, measure of variability, or statistical comparison for the primary outcome. As a result, the endpoint can be described by its intended measurement and timing, but its observed treatment effect cannot be interpreted.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical finding is that the registry record contains no collected data for the stated primary renal-function outcome. The planned measure was GFR at 36 months post-transplant, but the trial ended before any subject reached that timepoint. There is therefore no posted primary-outcome estimate to compare between the tacrolimus and everolimus arms, and no estimate of its precision.
This is different from a result showing that the treatments had similar renal function. A similarity conclusion would require outcome data and an analysis capable of estimating how large a difference remains compatible with those data. In the absence of collected primary-outcome values, the record cannot establish similarity, superiority, or a lack of effect. It also cannot show whether any difference would be clinically important.
The registry describes a randomized design, which can support a causal comparison when the planned outcomes are collected and the analysis is appropriate. Randomization does not create evidence about an outcome that was not measured. In this trial, the early termination and lack of primary-outcome data prevent that planned comparison from being made for long-term GFR.
The record lists adverse-event information for the two arms, including serious-event counts and selected serious-event terms. Those data concern safety reporting and do not substitute for the missing renal-function outcome. Nor can the adverse-event entries establish the overall balance of benefit and harm; the registry record does not provide a complete account of all clinical outcomes or a statistical analysis of the primary endpoint.
The record also lists two outcome measures and no analyses. It does not report a treatment-effect estimate, confidence interval, p-value, or analysis population for the primary outcome. A confidence interval, in general, conveys the range of effect values compatible with the observed data under the analysis assumptions. Without outcome observations and an analysis, no such range can be interpreted for the stated endpoint.
The enrollment entry is 14, but the primary-outcome description does not say that any participant contributed a 36-month GFR observation; it explicitly says no data were collected for that measure. Thus, the enrollment figure should not be read as the number analyzed for the primary outcome. The record’s the registry entries support a conclusion about the absence of a primary result, not a conclusion about the direction or size of a treatment effect.
9. Statistical Methods Explained
What does randomization contribute?
Randomization assigns participants to treatment groups using a chance-based process. In general, it is used to reduce systematic differences between groups at the start of a trial, so a later outcome comparison can be interpreted more credibly as a treatment comparison. It does not guarantee that groups will be identical, particularly in a small trial, and it cannot correct for an outcome that was never collected. The registry identifies the study as randomized, but the specific sequence-generation and allocation-concealment methods are not reported in the registry record.
What does the parallel design mean?
In a parallel-group design, participants are assigned to a treatment group and the groups are compared over the study period. Here, the recorded arms are tacrolimus maintenance immunosuppression and everolimus monotherapy maintenance immunosuppression. The registry lists no masking. Masking can reduce the influence of knowledge of treatment assignment on care or outcome assessment, depending on who is masked and how outcomes are measured. The registry record does not report whether outcome assessors were masked or describe procedures to limit assessment bias.
What would a treatment-effect estimate mean?
For a continuous outcome such as GFR, an analysis might estimate a difference in the outcome between treatment groups at a specified time, or estimate a difference in change over time. Which approach is appropriate depends on the measurement schedule and prespecified analysis. The registry entries do not report the planned estimator, covariate adjustment, or statistical model. Because no GFR data were collected for the stated 36-month outcome, there is no posted estimate to interpret under any of these approaches.
A confidence interval is a general statistical tool for expressing uncertainty around an estimate. A narrow interval indicates greater precision than a wide interval, while the interval’s position indicates which effect values are compatible with the data and method. An interval is not a guarantee about the true effect. No confidence interval for the primary endpoint is reported in the registry record, because the record states that the outcome data were not collected.
What do the planning illustrations represent?
The registry’s planning assumptions describe an illustration based on an observed effect, rather than the trial’s own design. The assumptions specify a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Under the described convention, time-to-event planning uses a total event count, while other planning results use participants per arm. These assumptions describe how a planning illustration is framed; they do not establish that the trial used those methods to choose its enrollment.
Sample-size illustrations are planning aids, not statements of what a trial observed. They are not observed power, and they do not supply missing outcome data. The primary endpoint has no collected GFR observations in the registry record, so no primary-outcome effect can be interpreted from the posted results. The registry entries do not report a trial-specific sample-size justification or target based on a prespecified treatment effect. Any planning illustration should therefore be kept separate from the actual enrollment and from conclusions about the treatment comparison.
Why does over-dispersion matter in general?
Over-dispersion is a general concern when count data vary more than a statistical model expects. If that extra variability is ignored, estimated uncertainty can be too small and statistical evidence can appear stronger than warranted. Whether over-dispersion applies depends on the outcome type and model. The registry record does not report a primary-outcome count model or an analysis in which over-dispersion was assessed; the stated primary measure is GFR, and no data were collected for it.
What cannot be inferred from the registry entry?
The registry record does not report the prespecified statistical analysis plan, handling of missing observations, rules for the analysis population, interim analyses, or multiplicity procedures. It also does not report the primary outcome’s observed variability or a comparison estimate. Without those details and the outcome data, readers cannot reconstruct the intended analysis or determine how its assumptions would affect the treatment-effect estimate. General statistical methods can explain what such analyses might do, but they cannot replace an unreported plan or an unobserved result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures and no analyses. The primary outcome is described as GFR at 36 months post-transplant, but the record states that the trial was terminated before any subject reached that timepoint and that no data were collected for the measure. The registry record therefore does not report a primary-outcome analysis, an analysis population, or a treatment-effect estimate.
Multiplicity arises when a trial tests multiple outcomes, timepoints, subgroups, or statistical hypotheses. In general, conducting multiple tests can increase the chance of finding a nominally unusual result by chance, so a prespecified strategy may be used to control or interpret that risk. The registry record does not report a multiplicity strategy or explain how the listed outcome measures were prioritized or analyzed.
Missing-data methods address outcomes that were intended to be collected but are unavailable for some participants. In general, the suitability of a method depends on why data are missing and on assumptions about the unobserved values. Here, the registry explicitly states that no data were collected for the primary outcome because the trial ended before the relevant timepoint. It does not report a missing-data method, and no method can recover observed 36-month GFR values from this record.
The registry record does not report whether analyses were intended to follow assigned treatment, actual treatment received, or another analysis population. It also does not report interim analyses or stopping rules. These omissions limit assessment of the planned statistical procedures, but they do not change the key interpretation: the stated primary endpoint has no collected data in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Control Arm | 2 | 6 | 33.3% |
| Study Arm | 1 | 8 | 12.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Control Arm | 0 of 6 |
| Study Arm | 0 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Control Arm | 0 of 6 |
| Study Arm | 0 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Control Arm | Study Arm |
|---|---|---|---|
| Lung Infection | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 1 of 8 |
| Liver Infection | Hepatobiliary disorders | 1 of 6 | 0 of 8 |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | 1 of 6 | 0 of 8 |
Serious events with the highest arm-level rate: liver infection (16.7%), pleural effusion (16.7%), lung infection (12.5%).
The registry lists serious adverse-event information by arm. The control arm entry records 2 participants affected by serious adverse events among 6 at risk; the study arm entry records 1 among 8 at risk. The record lists 0 participants affected by other adverse events in each arm and 0 deaths in each arm. These are descriptive entries, not an adjusted comparison or a test of a treatment difference.
The listed serious-event terms include Liver Infection at 16.7%, Pleural Effusion at 16.7%, and Lung Infection at 12.5%. These percentages should be read as the registry’s reported figures. The record does not provide additional detail about event timing, severity grading, recurrence, relatedness to treatment, or how the listed terms were selected. They should not be treated as a complete description of all safety outcomes.
Small group counts make adverse-event comparisons especially uncertain. A difference in the number of affected participants does not by itself establish that one regimen caused more or fewer events. The registry record does not report a statistical comparison or an analysis accounting for exposure duration. The serious-event entries also cannot compensate for the absence of the planned 36-month renal-function data.
12. What the Result Does, and Does Not, Mean
The record documents a randomized, parallel-group comparison of tacrolimus maintenance immunosuppression with everolimus monotherapy after liver transplantation. It also documents that the trial was terminated and that no data were collected for the stated primary measure of GFR at 36 months post-transplant. That is the main limitation on what can be concluded about the intended renal-function comparison.
The record does not show that everolimus improved renal function, that tacrolimus worsened it, or that the regimens produced equivalent outcomes. Each of those claims would require relevant outcome observations and an analysis. The absence of a reported primary result is not evidence that there was no treatment effect; it is an absence of evidence for that endpoint in this registry record.
The listed safety entries describe serious adverse events and deaths as recorded by arm, but they do not provide a complete treatment-effect assessment. They do not answer the primary renal-function question, and the record does not report an inferential comparison of the safety entries. Conclusions about overall clinical benefit or harm are therefore not supported by these registry entries.
The brief summary explains why investigators proposed removing tacrolimus from maintenance immunosuppression, including concern about nephrotoxicity and a rationale involving induction immunosuppression. Such rationale motivates a trial but is distinct from its results. The registry’s trial-specific primary endpoint remains unobserved, so the proposed biological or clinical rationale should not be confused with evidence that the strategy achieved its intended effect in this study.
Statistically, the appropriate reading is limited: the record describes the design and reports some safety information, but it does not provide the planned long-term renal-function result. The results cannot establish a direction, size, or precision of effect on GFR.
13. Why This Trial Matters Statistically
This trial illustrates why a randomized design and a clinically motivated question are not enough to produce an interpretable primary-outcome estimate. Randomization supports a fair treatment comparison when outcome data are collected and analyzed. The registry record says that the trial ended before any subject reached the planned 36-month GFR timepoint, leaving the primary comparison without observations.
The distinction between an unobserved result and a null result is important for clinical research. A null or inconclusive estimate still depends on collected data and has some degree of precision. In this record, there is no primary-outcome estimate to judge for size, direction, or uncertainty. Treating this as evidence of no difference would confuse failure to observe the outcome with an observed estimate near no difference.
The record also highlights the value of transparent reporting about why a trial stops, what outcomes were collected, and which analyses were completed. The status is terminated, but the reason for termination is not reported in the registry record. Further reporting on the analysis plan, missing data, and available outcomes would help readers understand the trial’s conduct and the limits of its safety information.
For statistical interpretation, the trial is therefore informative about the intended design and the absence of the primary endpoint result, rather than about the comparative renal effect of the two maintenance regimens. Keeping those roles distinct prevents the rationale, design, and adverse-event entries from being mistaken for a demonstrated primary treatment effect.
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 most consequential limitation is explicit: the trial ended before any subject reached the 36-month primary-outcome timepoint, and no data were collected for that endpoint. There is no posted GFR estimate, measure of variability, confidence interval, or statistical comparison. The primary treatment question cannot be answered from this record.
The registry reports enrollment of 14, but does not describe the number assigned to each arm in the registry record, the number receiving each treatment, or the number included in any analysis. The adverse-event entries give at-risk figures by arm, but these should not be substituted for an analysis population for the primary outcome. Treatment exposure duration is not reported in the registry record.
The trial’s terminated status is reported, while the reason for termination is not reported in the registry record. The registry also does not report detailed eligibility criteria, the treatment schedules, adherence, changes in assigned treatment, the randomization procedure, or allocation concealment. These gaps restrict evaluation of how the trial was conducted and which patients its findings might represent.
The primary-outcome title refers to tacrolimus monotherapy, while the recorded control and study arms are tacrolimus maintenance and everolimus monotherapy, respectively. The endpoint description identifies GFR, but the record does not clarify the title wording. The registry does not report the statistical analysis plan, missing-data procedures, multiplicity handling, interim analyses, or analysis populations. Those limitations further restrict assessment of intended analyses; however, the absence of primary endpoint data alone is sufficient to prevent interpretation of the planned renal-function comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Everolimus Monotherapy as Immunosuppression After Liver Transplant — NCT04063865.
- Registry record last updated 2023-05-23; status last verified 2023-04.
- Results first posted 2023-05-23.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry identifies a randomized, unmasked, parallel-group Phase 3 trial sponsored by Indiana University, with an enrollment of 14 and a terminated status. The comparison was tacrolimus maintenance immunosuppression in the control arm versus everolimus monotherapy maintenance immunosuppression in the study arm.
The primary outcome description names GFR at 36 months post-transplant. The record states that the trial ended before any subject reached that timepoint and that no data were collected for the outcome. It lists two outcome measures and no analyses. Serious adverse-event entries are reported by arm, but the registry does not report a statistical comparison of the primary endpoint.
The trial’s rationale concerns long-term renal function after liver transplantation, but the posted record does not establish the effect of either regimen on that outcome. Its central statistical limitation is the absence of collected primary-outcome data.