Comparison of CNI-based Regimen Versus CNI-free Regimen in Kidney Transplant Recipients.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of CNI-based Regimen Versus CNI-free Regimen in Kidney Transplant Recipients. (NCT00332839), a randomized phase 4 study. The primary outcome is Renal Function.

2. Clinical Question

The study was designed to assess whether the CNI-free regimen was as safe and well tolerated as standard therapy without compromising therapeutic efficacy, while potentially improving renal function. Those aims describe the question the investigators intended to address; they are not findings. The registry does not report a primary renal-function estimate or a comparison between groups for that endpoint.

Other listed outcomes include biopsy-proven acute rejection, graft loss and death; treatment failures; renal-function evolution; adverse events and death; cardiovascular risk; and proteinuria. The record therefore identifies a broader set of clinical concerns, but the available primary-outcome description does not establish whether either regimen was better on any of them.

3. Trial Design

This was a Phase 4, randomized, parallel-group study with no masking. It was described as multicenter, open-label and prospective. The registry lists enrollment of 93 and gives the condition as Renal Transplantation. The sponsor was Novartis Pharmaceuticals. The recorded start was 2005-11, primary completion was 2013-03, and the status is Terminated.

The CNI group received enteric-coated mycophenolate sodium and corticosteroids alongside cyclosporine A or tacrolimus, according to the arm description. Participants in the Certican group were switched in a step-wise fashion from the CNI-based regimen to everolimus. The registry's intervention list also includes these medicines and corticosteroids. Because the study was open-label, masking was not used; the record does not describe additional procedures to conceal treatment assignment.

Random allocation is intended to create groups that are comparable on average at the start of a study, reducing the risk that treatment selection is related to participant characteristics. It does not guarantee that every characteristic will be balanced, particularly in a study with limited recruitment. Parallel-group designs assign participants to treatment strategies that are compared over the same study period, rather than having each participant receive both strategies.

The registry says the primary renal-function analysis was not performed because recruitment was too low for an efficacy analysis to be powered. The reason for termination beyond the details stated in the record, the randomization procedure, allocation concealment, and any protocol changes are not reported in the registry record. The record also does not describe the timing or duration of follow-up for the secondary outcomes in the information.

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.

Core (Months 0 - 12)

Reasons for not completing this period:

Follow-up (Months 12 - 60)

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Renal Function, measured over 12 months.

The primary endpoint was titled Renal Function, with a timeframe of 12 months. Renal function is a clinical measure of how well the kidneys perform. In a transplant study, comparing renal function can help assess changes in the transplanted kidney under different treatment strategies. That is the general rationale for using such an endpoint; the registry does not specify the particular renal-function measure, unit, or summary statistic planned for this outcome.

The registry explicitly states that the analysis for this outcome was not performed because analyses could not be powered for efficacy due to low recruitment. Consequently, there is no reported primary endpoint estimate, uncertainty interval, or statistical comparison to interpret. The endpoint name and timeframe indicate what the study intended to assess, not what the data demonstrated.

Without a reported measure and group-level result, it is not possible to tell from the registry record how renal function changed, how much any observed difference varied, or whether the results were compatible with a range of clinically important effects. In general, a numerical estimate describes the observed contrast, while a confidence interval conveys its statistical precision. Neither is reported for this primary endpoint.

The endpoint should therefore be read as a planned outcome rather than a completed efficacy result. The record's statement about low recruitment explains why the analysis was not performed; it does not supply evidence for or against either treatment strategy.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to treatment groups by chance rather than by a clinician's or participant's choice. In general, this helps reduce systematic differences between groups at baseline. It does not ensure that groups are identical, and it cannot correct every problem that arises after assignment, such as missing outcome measurements or changes in treatment. This study is identified as randomized, but the details of sequence generation and allocation concealment are not reported in the registry record.

What does the parallel-group design mean?

In a parallel-group study, each group follows its assigned treatment strategy during the study, and outcomes are compared across groups. Here, the record describes a CNI-based group and a Certican group in which participants were switched step-wise to everolimus. The design is also described as open-label, meaning masking was not used. In general, knowledge of assigned treatment can influence care, reporting, or assessment, depending on the outcome and study procedures. The registry does not report whether any specific safeguards were used to reduce such influences.

What does the missing primary analysis imply?

The primary outcome was renal function at 12 months. The registry says its analysis was not performed because recruitment was too low for the efficacy analysis to be powered. In general, statistical power is the probability that a study will detect a specified effect under stated assumptions when that effect is present. It depends on factors such as the amount of information collected, variability, the effect being sought, and the analysis plan. A study described as insufficiently powered may have difficulty distinguishing an effect from random variation. In this record, however, no primary estimate or test is reported, so there is no result from which to assess the size or precision of a renal-function contrast.

Power is not a measure of whether a treatment is effective, and a lack of a powered analysis does not prove that no effect exists. Likewise, a sample-size calculation is a planning exercise, not an observed treatment result. The registry does not report a sample-size justification for the primary endpoint or the statistical plan used for it. The reason for the low recruitment is not reported in the registry record.

How should estimates and confidence intervals be read?

As a general statistical concept, an estimate summarizes the observed difference or association in a sample. A confidence interval describes the uncertainty around that estimate under the assumptions of the analysis. A narrow interval indicates greater statistical precision than a wide interval, but precision alone does not determine clinical importance. Since the primary renal-function analysis was not performed, the registry supplies neither an estimate nor a confidence interval for that outcome. There is therefore no basis to describe the size or precision of the primary comparison.

A p-value, when reported, addresses how compatible the data are with a specified null hypothesis under a statistical model; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. No primary-outcome p-value is reported. The registry also lists no analyses in the record's analysis summary. That absence should not be interpreted as proof that no analysis of any kind was ever conducted outside the registry; it means the record does not provide one.

What can adverse-event counts tell us?

Counts of participants with events describe how many people in each group were recorded as affected. They are not automatically measures of event rates over time, because timing and exposure duration may matter. In general, adverse events can also differ in severity, recurrence, and relationship to treatment. Those details are not fully reported in the registry record. The listed counts can be described as recorded, but they do not by themselves establish causation or a statistically reliable difference between strategies.

The record gives serious-event and other-event counts with participants at risk in each group, and lists several serious event terms with percentages. The terms are not identified by treatment group in the available information. The registry does not report comparative estimates, confidence intervals, or statistical tests for these safety data. Death counts are not reported in the adverse-event data.

Why does the analysis plan matter?

A prespecified analysis plan identifies the outcome definitions, populations, statistical methods, and handling of incomplete observations before results are examined. This can help limit selective reporting and clarify how results should be interpreted. The record does not report the statistical analysis plan, outcome measurement details, or analysis populations. It is therefore not possible to assess whether the planned analyses changed, how missing measurements were handled, or whether any adjusted analyses were intended.

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. Ignoring it can make uncertainty appear too small. The registry does not report the distribution or specific measurement for renal function, so no conclusion about whether over-dispersion was relevant to this endpoint can be drawn. More broadly, a statistical method can only be assessed when its assumptions, inputs, and results are documented; those details are not reported for the unperformed primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary renal-function endpoint. When multiple outcomes are tested, the chance of finding at least one apparently notable result by chance can increase. Statistical approaches can address multiplicity, but the appropriate approach depends on the prespecified questions and analysis plan. That plan, including any multiplicity adjustment or hierarchy among outcomes, is not reported in the registry record.

The primary endpoint analysis was not performed because recruitment was too low for an efficacy analysis to be powered. The registry does not provide results for the listed secondary outcomes in the information, so there is no basis to evaluate how multiplicity was handled in practice or to interpret a set of secondary comparisons. The record lists zero analyses in its analysis summary; this does not establish whether analyses exist outside the registry record.

Missing-data methods are also not reported. The record does not state how many primary outcome measurements were available at 12 months, whether participants discontinued or changed treatment, or how incomplete observations were handled. In general, missing data can affect both the precision and validity of a comparison, particularly when the reasons for missingness are related to outcomes or treatment. Without details, the direction and magnitude of any such influence cannot be assessed.

The analysis populations are not described in the available registry information. For example, it is not reported whether analyses were intended to include all randomized participants according to assigned group or only participants meeting additional criteria. These are general distinctions in trial analysis; no particular population or method should be inferred for this study.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary tract infection (6.5%), diarrhoea (4.3%), blood creatinine increased (4.3%), cardiac arrest (2.2%), coronary artery disease (2.2%).

The registry reports serious adverse events affecting 11 of 47 participants in the CNI group and 12 of 46 in the Certican group. It also reports other adverse events affecting 31 of 47 participants in the CNI group and 41 of 46 in the Certican group. These are descriptive participant counts, not adjusted comparisons or conclusions about treatment effects.

The registry lists urinary tract infection at 6.5%, diarrhoea at 4.3%, blood creatinine increased at 4.3%, cardiac arrest at 2.2%, coronary artery disease at 2.2%, and dyspepsia at 2.2% among the top serious event terms. The available information does not identify the treatment group for each term. Death counts are not reported in the adverse-event data.

In general, adverse-event counts need context: how events were defined and collected, whether they occurred once or repeatedly, the time at risk, and whether investigators judged them related to treatment. Those details and statistical comparisons are not reported in the registry record. The counts therefore describe what was recorded, but do not establish causation or a reliable difference in safety between the regimens.

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

The record establishes that a randomized, open-label, parallel-group trial was intended to compare a CNI-based regimen with a CNI-free regimen in stable renal transplant patients. It also establishes that renal function at 12 months was the primary outcome and that the planned efficacy analysis was not performed because recruitment was too low. These registry entries describe the study and its reporting; they do not provide an efficacy result.

The absence of a primary analysis means the registry cannot show how renal function compared between groups, how precise a comparison might have been, or whether the data support a specific treatment-effect conclusion. It does not mean that the groups were equivalent, that the treatments had no effect, or that either strategy was better. Such conclusions require reported estimates and appropriate uncertainty assessment.

The stated goal of assessing safety and tolerability without compromising efficacy, while improving renal function, is an objective rather than a finding. The adverse-event counts provide descriptive information, but they do not establish that a regimen caused events or that a difference between groups is reliable. The record does not report death counts in the adverse-event data or comparative safety analyses.

The registry lists additional outcomes, including rejection, graft loss, death, treatment failures, renal-function evolution, cardiovascular risk, and proteinuria. Their inclusion indicates areas the study intended to examine, but outcomes without reported comparative results cannot answer those questions. The record's terminated status and its statement about low recruitment help explain why the primary efficacy analysis was not completed; they do not resolve the clinical question.

Accordingly, the posted record is informative about study design, treatment strategies, the planned endpoint, and some adverse-event counts. It is not a completed comparative assessment of renal-function efficacy. Any interpretation should keep the distinction between intended objectives, descriptive safety information, and analyzed outcomes explicit.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registry identifies a randomized comparison and a clinically relevant primary outcome, but also states that the primary efficacy analysis was not performed. That combination illustrates why a trial's design and its results must be considered separately. Randomization describes how participants were assigned; it does not by itself produce an interpretable treatment-effect estimate.

Recruitment is important to the information a study can provide. The record says recruitment was too low for the renal-function efficacy analysis to be powered. In general, limited recruitment can reduce precision and make it harder to distinguish a true effect from random variation. In this case, the issue is more direct: the registry says the analysis was not performed, so no primary estimate or uncertainty interval is available to evaluate.

The record also highlights the difference between a study objective and a conclusion. The goal of assessing whether the CNI-free regimen could preserve efficacy while improving renal function is not evidence that it did so. Likewise, descriptive adverse-event counts do not establish comparative safety. Statistical interpretation depends on reported outcome definitions, analysis methods, and uncertainty, not on the wording of the research aim.

Finally, the record illustrates the limits of registry reporting for understanding analysis decisions. Details about the statistical plan, missing data, and analysis populations are not reported. Their absence makes it harder to assess how the intended questions were to be answered. The lesson is not a conclusion about either regimen, but a reminder that design information, outcome reporting, and sufficiently informative analyses each play distinct roles in clinical evidence.

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 that the registry states the primary renal-function analysis was not performed because recruitment was too low for an efficacy analysis to be powered. No estimate, confidence interval, or statistical comparison for the primary endpoint is reported. The specific renal-function measure and unit are also not reported in the registry record, which limits understanding of exactly what was intended to be measured.

The record does not report the statistical analysis plan, analysis populations, handling of missing observations, or whether outcome assessments were complete at 12 months. It also does not describe the randomization sequence or allocation concealment. These omissions prevent a detailed appraisal of how the planned comparison would have been conducted and how incomplete data might affect interpretation.

The study was open-label, so masking was not used. In general, knowledge of assignment can affect care and outcome assessment, although the extent depends on the outcome and safeguards. Those safeguards are not reported. The record is described as terminated, but its stated explanation for the unperformed efficacy analysis is low recruitment; further reasons for termination are not reported in the registry record.

Safety information is limited to the listed participant counts and event terms. The registry does not report comparative statistical analyses, event timing, exposure duration, or death counts in the adverse-event data. The treatment group associated with each listed serious event term is not identified in the available information. These limitations mean the counts should be read descriptively rather than as evidence of causation or a definitive difference between groups.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparison of CNI-based Regimen Versus CNI-free Regimen in Kidney Transplant Recipients. — NCT00332839.
• Registry record last updated 2014-08-28; status last verified 2014-08.
• Results first posted 2014-08-28.
• 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

NCT00332839 is a Phase 4, randomized, open-label, parallel-group study of CNI-based and CNI-free regimens in stable renal transplant patients. The registry reports enrollment of 93, a start of 2005-11, primary completion of 2013-03, and status Terminated. The sponsor was Novartis Pharmaceuticals.

The primary outcome was renal function at 12 months. The registry states that its analysis was not performed because recruitment was too low for an efficacy analysis to be powered. The specific measure, unit, and comparative result are not reported. Listed secondary outcomes include rejection, graft loss, death, treatment failures, renal-function evolution, adverse events, cardiovascular risk, and proteinuria.

Serious and other adverse-event counts are reported by group, along with a list of serious event terms and percentages. The record does not provide comparative safety analyses or death counts in the adverse-event data. The statistical plan, missing-data methods, and analysis populations are not reported in the registry record.