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 Efficacy and Safety Study of Everolimus Plus Reduced Cyclosporine Versus Mycophenolic Acid Plus Cyclosporine in Kidney Transplant Recipients (NCT00251004), a randomized phase 3 study. The primary outcome is Number of Participants With Composite Efficacy Endpoints - 12 Month Analysis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00251004 |
| Phase | Phase 3 |
| Condition | Kidney Transplantation, Graft Rejection |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 833 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis |
| Results posted | Yes |
2. Clinical Question
Population
De novo renal transplant recipients are the study population described in the official title. The registry record identifies kidney transplantation and graft rejection as conditions and reports total enrollment of 833. Further eligibility details are not reported in the registry record.
Intervention
Two regimens used concentration-controlled everolimus with reduced-dose cyclosporine A (CsA), alongside basiliximab and optional corticosteroids. The listed everolimus starting doses were 1.5 mg/day and 3.0 mg/day. The CsA dose was adjusted to target trough concentrations; the full target schedule is not completely available in the registry record.
Comparator
The control regimen used 1.44 g mycophenolic acid (MPA) as the sodium salt with standard-dose CsA, basiliximab, and optional corticosteroids. CsA dosing was adjusted to trough targets, but the full target schedule is not reported in the registry record.
Primary question
At 12 months, how many participants experienced primary efficacy failure, defined as treated biopsy-proven acute rejection, graft loss, death, or loss to follow-up? The study description identifies this endpoint, but the observed group results and comparative estimates are not reported in the registry record.
The clinical question is a comparison among three immunosuppressive regimens following kidney transplantation, rather than a comparison of everolimus with no immunosuppression. Each regimen included basiliximab, and corticosteroids could also be used. The two everolimus regimens paired different starting doses with reduced-dose CsA; the control paired MPA with standard-dose CsA. Because both the accompanying drug and the intended CsA dosing strategy differ between the everolimus regimens and control, the comparison concerns whole treatment strategies. It cannot isolate the effect of everolimus alone from the effect of changing the CsA strategy.
The registry record describes the primary endpoint as a composite assessed at 12 months in the intention-to-treat population. Its components capture several distinct events: treated biopsy-proven acute rejection, graft loss, death, and loss to follow-up. The question therefore concerns whether participants experienced any event meeting the composite definition, not a single biological outcome. The component definitions matter when interpreting what a composite count represents.
The posted record does not give the number of primary endpoint events in each group, an effect estimate, a confidence interval, or a significance test. It therefore does not permit a conclusion about the relative observed primary outcome across these regimens. The registry also lists secondary outcomes concerning a composite of graft loss, death, or loss to follow-up at 12 months and non-inferiority analysis of renal function measured by calculated glomerular filtration rate. Results for those outcomes are not reported in the registry record.
3. Trial Design
This was a phase 3, randomized, parallel-group study with no masking, according to the registry record. The stated enrollment was 833. The record marks the study completed and gives its start as 2005-10 and primary completion as 2009-08. Those dates describe the registry record and do not establish when results became available or whether all planned analyses were completed.
Three treatment groups are described: low-dose everolimus with reduced-dose CsA, high-dose everolimus with reduced-dose CsA, and MPA with standard-dose CsA. Basiliximab was included in each regimen, and corticosteroids were optional. The official title characterizes the everolimus treatments as concentration-controlled, with starting doses of 1.5 and 3.0 mg/day, and the comparator as 1.44 g MPA. The registry describes CsA dose adjustments according to trough targets. Some arm descriptions are incomplete, so the full dosing schedules and target ranges are not reported in the registry record.
Randomization is a design feature intended to make treatment groups comparable, on average, with respect to measured and unmeasured baseline factors. That is a general statistical rationale, not evidence that the groups in this trial were balanced: baseline characteristics and allocation details are not reported in the registry record. The record does not state the allocation ratio, randomization procedure, concealment method, or whether randomization was stratified.
With no masking, participants and study personnel were not masked to group assignment according to the registry record. General methodological consideration: knowledge of assigned treatment can affect care, outcome assessment, or reporting, although the extent depends on the outcome and safeguards used. Whether endpoint assessors were masked or whether other protections were used is not reported in the registry record.
The primary endpoint was assessed at 12 months in an intention-to-treat population. The registry lists four outcome measures and six analyses, but the details of the full analysis plan, any analysis hierarchy, and the allocation of analyses to outcomes are not reported in the registry record. The stated design makes it possible to ask about both efficacy and safety, but the posted record does not provide the primary outcome results needed to assess comparative efficacy.
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 | Low-dose Everolimus Group | High-dose Everolimus Group | Control Group |
|---|---|---|---|
| STARTED | 277 | 279 | 277 |
| 12 Month Analysis | 241 | 249 | 253 |
| 24 Month Analysis | 232 | 238 | 246 |
| COMPLETED | 232 | 238 | 246 |
| NOT COMPLETED | 45 | 41 | 31 |
Reasons for not completing this period:
| Reason | Low-dose Everolimus Group | High-dose Everolimus Group | Control Group |
|---|---|---|---|
| Withdrawal by Subject | 23 | 16 | 14 |
| Death | 9 | 10 | 8 |
| Lost to Follow-up | 1 | 2 | 1 |
| Graft Loss | 12 | 13 | 8 |
Analysis population for the primary outcome, as defined in the registry: Intention-to-treat (ITT) population
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 | Low-dose Everolimus Group | High-dose Everolimus Group | Control Group | Total |
|---|---|---|---|---|---|
| Participants analysed | 277 | 279 | 277 | 833 | |
| Age Continuous | Years | 45.7 (SD 12.72) | 45.3 (SD 13.36) | 47.2 (SD 12.74) | 46.1 (SD 12.95) |
| Sex: Female, Male: Female | Participants | 100 | 88 | 88 | 276 |
| Sex: Female, Male: Male | Participants | 177 | 191 | 189 | 557 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Composite Efficacy Endpoints - 12 Month Analysis, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with a composite efficacy failure at 12 months. A participant counted as having an event if the participant experienced treated biopsy-proven acute rejection, graft loss, death, or loss to follow-up, as described in the registry record. The population specified for this endpoint is intention-to-treat.
The record defines treated biopsy-proven acute rejection as a biopsy graded IA, IB, IIA, IIB, or III that was treated with anti-rejection therapy. Graft loss was defined as the allograft being presumed lost on the day dialysis began, with no subsequent removal from dialysis and no retransplantation. The registry wording thus includes clinical and treatment-related criteria, not simply any biopsy finding or temporary dialysis.
General statistical explanation: a composite endpoint can represent several clinically relevant ways an outcome may occur and can increase the number of participants with an event available for analysis. Its interpretation depends on the components: components can differ in frequency, severity, and meaning, and a composite count does not show which component drove any group result. Component-specific counts are useful for understanding that mix.
The endpoint definition is available, but group counts and comparative results are not reported in the registry record. Without them, the endpoint cannot establish whether event frequency differed between regimens or how precise any difference might be.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial question and the definition of its primary endpoint, but it does not report the observed primary endpoint results. In particular, the number of participants with an event in each group, a between-group estimate, a confidence interval, and a p-value are not reported in the registry record. Consequently, the posted information does not support a statistical conclusion about the direction, size, or precision of a primary endpoint difference.
The endpoint is a composite of treated biopsy-proven acute rejection, graft loss, death, and loss to follow-up. General statistical interpretation: a composite result, when available, would describe the combined occurrence of its qualifying events. It would not by itself show whether a difference arose from rejection, graft loss, death, or loss to follow-up. Separate component results can help determine whether the overall pattern is consistent across components or driven mainly by one of them. Those component results are not reported in the registry record.
The registry identifies an intention-to-treat population for the primary endpoint. In general, intention-to-treat analysis retains participants in their randomized groups for analysis, which aims to preserve the comparison created by randomization. The exact handling of participants with missing endpoint information, deviations from assigned treatment, or other analysis issues is not reported in the registry record. The term alone does not reveal how missing outcomes were handled.
The record lists secondary outcomes concerning a composite of graft loss, death, or loss to follow-up at 12 months and non-inferiority analysis of renal function measured by calculated glomerular filtration rate using the MDRD formula. Their observed results, analysis estimates, and uncertainty are not reported in the registry record. The registry also lists safety data, which are described separately; those counts do not substitute for the missing primary efficacy comparison.
The enrollment figure of 833 is a design and registry descriptor, not an outcome result. Group sizes listed in the adverse-event information refer to participants at risk for those safety summaries; they should not be treated as primary endpoint denominators. The posted information does not explain the difference, if any, between total enrollment and the populations used for particular outcome summaries.
General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity, with narrower intervals indicating greater precision under the model and assumptions used. A p-value addresses compatibility of data with a specified null hypothesis under an analysis model; it does not measure clinical importance or the probability that a treatment is effective. Neither measure is available for the primary comparison in the registry record, so no inference based on either can be made from this record.
There is also no basis in the posted primary outcome information for declaring similarity, superiority, or non-inferiority among regimens. Such claims require the appropriate estimates and, for non-inferiority, a prespecified margin and analysis plan. Those details and results are not reported in the registry record.
9. Statistical Methods Explained
General statistical explanation: the appropriate interpretation of a clinical trial depends on its design, endpoint definition, analysis population, and the uncertainty around estimated effects. The registry record identifies some of these elements, but it does not report the primary efficacy estimates or several details of the statistical plan. The following concepts explain how the reported design features relate to interpretation; they do not describe unreported analyses as having been performed.
What does randomization contribute?
Random assignment is used to create treatment groups whose baseline prognostic characteristics are comparable on average. If allocation is properly implemented and outcomes are analyzed in a way that respects assignment, differences in outcomes can be interpreted as evidence about the assigned treatment strategies, subject to random variation and study limitations. Randomization does not guarantee identical groups, nor does it prevent bias arising after assignment. The registry identifies the study as randomized but does not report the sequence-generation method, concealment, allocation ratio, or baseline group characteristics.
General statistical explanation: the parallel-group structure means participants are assigned to a regimen and followed in that group, rather than crossing between regimens as part of the design. The record lists three parallel groups. It does not report whether all pairwise contrasts were planned, whether one comparison was designated primary among the three groups, or how any multiple comparisons were to be addressed.
What does the composite endpoint capture?
The primary outcome is a participant count for a composite event at 12 months. The event definition combines treated biopsy-proven acute rejection, graft loss, death, and loss to follow-up. The record gives specific criteria for treated rejection and graft loss. A composite can provide a single summary across several event types, but it can obscure differences among components. General statistical practice is to inspect both the composite and its components when the data permit, because a combined result can be influenced more by common components than by rare components. The registry does not report component counts for this primary endpoint.
The outcome is described as a number of participants, with the intention-to-treat population specified. A count alone is not a comparative effect estimate. To compare groups, an analysis generally also needs the relevant group denominators and a defined statistical contrast, such as a difference in event proportions or another measure appropriate to the design. No primary group counts or effect estimates are reported in the registry record, so no such contrast can be interpreted from the posted primary result.
How should uncertainty be assessed?
General statistical explanation: estimates from a sample are subject to random variation. A confidence interval describes a range of values reasonably compatible with the data and the chosen model at a stated confidence level. Its width reflects precision, while its position relative to a null value can inform interpretation of a comparison. A p-value is a measure of how unusual data would be under a specified null hypothesis and model. It does not indicate the size or importance of an effect. The registry record does not report a confidence interval or p-value for the primary endpoint.
When several groups or outcomes are examined, the chance of at least one apparently notable result can increase if no adjustment or hierarchy is used. General statistical approaches include prespecifying a primary contrast, controlling a family-wise error rate, or treating secondary analyses as exploratory. Which approach, if any, was planned for this trial is not reported in the registry record. The number of listed outcome measures and analyses does not by itself reveal how multiplicity was managed.
What can the sample-size assumptions tell readers?
The registry describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration is described as a total event count using the Schoenfeld method; other illustrations are described as participants per arm. These assumptions describe a planning exercise, not necessarily the trial's original design.
General statistical explanation: power is the probability that a specified analysis will reject a null hypothesis under a specified alternative, given assumptions such as the effect size, variability, event rate, significance level, and sample size. A planning illustration can show how sample size would change under alternate assumed effects. It is not observed power and does not establish that a completed trial was adequately powered for its original objectives. The original sample-size justification, assumed effect, planned power, and any revisions are not reported in the registry record.
Because the planning illustration is derived from an observed effect, its interpretation depends on that effect estimate and on the assumptions used. General caution: observed effects can be imprecise, particularly when event counts are limited, and a planning calculation based on them is not independent confirmation of the result. The registry does not report the primary observed effect needed to assess this relationship.
Why can outcome distributions matter?
General statistical explanation: binary outcomes are often analyzed using methods appropriate to event counts or event probabilities. The chosen method may depend on the sample size, event frequency, follow-up structure, and whether adjustment for baseline factors is planned. When count data are over-dispersed, their variability exceeds what a simple model assumes; methods that account for extra variability can produce more appropriate uncertainty estimates. These concepts are general and do not imply that any particular model was used in this trial. The analysis model and any covariate adjustment are not reported in the registry record.
The primary endpoint has a fixed 12-month assessment description, while the listed renal-function outcome concerns calculated glomerular filtration rate. General statistical explanation: a continuous measure such as calculated filtration rate is interpreted through its scale, variation, and analysis contrast; non-inferiority additionally requires a prespecified margin defining how much difference would remain acceptable. The margin, model, and result for the renal-function analysis are not reported in the registry record. No non-inferiority conclusion can be drawn from the outcome title alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists four outcome measures and six analyses. It identifies the 12-month composite efficacy endpoint as primary and lists secondary outcomes involving graft loss, death, or loss to follow-up and calculated glomerular filtration rate. The record does not report a complete prespecified analysis plan, a hierarchy among outcomes or treatment contrasts, or a method for controlling multiplicity. The number of listed analyses alone does not establish whether multiplicity adjustment was necessary or performed.
General statistical explanation: testing multiple outcomes or comparisons can increase the chance of a false-positive finding if each is interpreted independently. Prespecification, hierarchical testing, or statistical adjustment are possible strategies, but the registry record does not say whether any of these were used. In the absence of that information, any unreported secondary findings cannot be placed in a clear confirmatory or exploratory framework.
The primary endpoint is assigned to the intention-to-treat population. This identifies the intended analysis population but does not describe the handling of missing data. Loss to follow-up is itself included as a primary composite component, yet the record does not explain how that component was operationalized, whether additional participants had incomplete endpoint data, or how missing observations were treated in analyses of other outcomes.
General statistical explanation: missing data can affect estimates when the likelihood of missingness is related to treatment, prognosis, or outcome. Common approaches depend on why data are missing and may include explicit event definitions, imputation, sensitivity analyses, or analyses of available observations. None of these approaches should be attributed to this trial without documentation. The missing-data assumptions and methods are not reported in the registry record.
The record also does not report whether analyses excluded participants after randomization, how treatment discontinuation or crossover was handled, or whether sensitivity analyses were conducted. These details are relevant to understanding departures from the intention-to-treat principle and the robustness of findings, but no conclusions about those practices can be drawn from the 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 |
|---|---|---|---|
| Low-dose Everolimus Group | 176 | 274 | 64.2% |
| High-dose Everolimus Group | 193 | 278 | 69.4% |
| Control Group | 168 | 273 | 61.5% |
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 |
|---|---|
| Low-dose Everolimus Group | 268 of 274 |
| High-dose Everolimus Group | 272 of 278 |
| Control Group | 264 of 273 |
Most frequent serious adverse event terms
| Event term | Organ system | Low-dose Everolimus Group | High-dose Everolimus Group | Control Group |
|---|---|---|---|---|
| Urinary tract infection | Infections and infestations | 20 of 274 | 22 of 278 | 25 of 273 |
| Blood creatinine increased | Investigations | 20 of 274 | 19 of 278 | 22 of 273 |
| Pyrexia | General disorders | 12 of 274 | 16 of 278 | 13 of 273 |
| Renal graft loss | Injury, poisoning and procedural complications | 14 of 274 | 18 of 278 | 9 of 273 |
| Lymphocele | Vascular disorders | 15 of 274 | 15 of 278 | 8 of 273 |
| Pneumonia | Infections and infestations | 8 of 274 | 13 of 278 | 12 of 273 |
| Complications of transplanted kidney | Injury, poisoning and procedural complications | 9 of 274 | 5 of 278 | 7 of 273 |
| Dehydration | Metabolism and nutrition disorders | 7 of 274 | 5 of 278 | 8 of 273 |
| Renal failure acute | Renal and urinary disorders | 6 of 274 | 7 of 278 | 7 of 273 |
| Gastroenteritis | Infections and infestations | 6 of 274 | 4 of 278 | 9 of 273 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Low-dose Everolimus Group | High-dose Everolimus Group | Control Group |
|---|---|---|---|---|
| Oedema peripheral | General disorders | 134 of 274 | 126 of 278 | 116 of 273 |
| Constipation | Gastrointestinal disorders | 107 of 274 | 125 of 278 | 116 of 273 |
| Nausea | Gastrointestinal disorders | 85 of 274 | 81 of 278 | 91 of 273 |
| Hypertension | Vascular disorders | 86 of 274 | 83 of 278 | 87 of 273 |
| Anaemia | Blood and lymphatic system disorders | 75 of 274 | 86 of 278 | 67 of 273 |
| Urinary tract infection | Infections and infestations | 62 of 274 | 59 of 278 | 60 of 273 |
| Diarrhoea | Gastrointestinal disorders | 59 of 274 | 52 of 278 | 65 of 273 |
| Hyperlipidaemia | Metabolism and nutrition disorders | 55 of 274 | 62 of 278 | 44 of 273 |
| Upper respiratory tract infection | Infections and infestations | 52 of 274 | 48 of 278 | 60 of 273 |
| Vomiting | Gastrointestinal disorders | 44 of 274 | 46 of 278 | 65 of 273 |
Serious events with the highest arm-level rate: urinary tract infection (9.2%), blood creatinine increased (8.1%), renal graft loss (6.5%), pyrexia (5.8%), lymphocele (5.5%).
The registry reports serious adverse-event information for the three groups. The low-dose everolimus group had 274 participants at risk and 176 with a serious adverse event; the high-dose everolimus group had 278 at risk and 193 affected; the control group had 273 at risk and 168 affected. These are group-level counts in the registry record. They do not describe the primary efficacy endpoint.
For other adverse events, the record reports 274 at risk and 268 affected in the low-dose everolimus group, 278 at risk and 272 affected in the high-dose everolimus group, and 273 at risk and 264 affected in the control group. These figures should be read using the registry's separate serious and other adverse-event categories, not as counts of distinct event episodes. The registry record does not explain in this information whether participants could contribute more than one event or how event attribution was determined.
The registry lists serious adverse-event terms with percentages: urinary tract infection, 9.2%; blood creatinine increased, 8.1%; renal graft loss, 6.5%; pyrexia, 5.8%; lymphocele, 5.5%; and pneumonia, 4.7%. The listed information does not give group-specific percentages for these terms. Death counts are not reported in the registry record.
General statistical explanation: safety counts are descriptive unless accompanied by a defined comparative analysis and uncertainty estimates. Differences in raw counts should not be interpreted as comparative risk estimates without suitable denominators, follow-up information, and methods. These safety figures alone do not establish that a regimen caused or prevented any event.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, unmasked, phase 3 study compared three immunosuppressive regimens after kidney transplantation. It describes a primary composite efficacy endpoint assessed at 12 months and identifies the intended population as intention-to-treat. It also reports group-level adverse-event counts and a list of serious adverse-event terms with percentages.
The record does not report the observed primary endpoint counts or a statistical comparison among groups. It also does not provide an effect estimate, confidence interval, or p-value for that endpoint. Therefore, the available information does not show whether the primary outcome differed among the regimens, how large a difference may have been, or how precisely it was estimated. The absence of a reported result is not evidence that the groups were equal.
The endpoint combines treated biopsy-proven acute rejection, graft loss, death, and loss to follow-up. Even if an overall composite result were available, component-level results would be needed to understand which events contributed to it. Those primary component results are not reported in the registry record. Secondary outcome titles, including a renal-function non-inferiority analysis, do not establish the findings or the statistical criteria used.
The safety counts describe affected participants in each group, but the record does not provide comparative estimates or uncertainty for these figures. The listed serious adverse-event percentages are not assigned to individual groups in the posted information. They should therefore be read as descriptive entries rather than as evidence of a comparative treatment effect.
General statistical explanation: a clinical trial can inform a treatment comparison only to the extent that its outcomes, methods, and uncertainty are reported. Randomization is an important design feature, but it does not replace outcome results or details of analysis. Likewise, a planning illustration based on an observed effect cannot be treated as observed power or as confirmation of a treatment effect.
No conclusion about efficacy, non-inferiority, or comparative safety can be drawn from the endpoint definition and design information alone. Such conclusions would require reported outcome estimates, uncertainty, and sufficient detail about the analyses and missing-data handling. Those elements are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable as a randomized comparison of three regimens rather than a single treatment-versus-control contrast. The two everolimus strategies differ in starting dose and share a reduced-dose CsA approach, while the MPA comparator uses standard-dose CsA. Consequently, any eventual contrast would concern the complete regimens, not the isolated effect of one drug independent of the CsA strategy.
The primary outcome also illustrates an important interpretive issue: a composite can summarize several clinically distinct events in one endpoint. Treated biopsy-proven acute rejection, graft loss, death, and loss to follow-up do not have identical meanings. A composite result would need to be understood alongside its components to show what kind of events contributed to the overall count. The component-level primary results are not reported in the registry record.
The registry's outcome listing distinguishes an efficacy composite from a renal-function non-inferiority analysis. General statistical explanation: non-inferiority is not established merely by observing a small difference or by naming a non-inferiority analysis. Interpretation depends on the prespecified margin, analysis population, estimate, and uncertainty. Those details and results are not reported in the registry record.
The record also illustrates the difference between a trial's design and its reported evidence. Randomization, phase, enrollment, and endpoint definitions describe how the study was characterized; they do not reveal the treatment effect. Without primary estimates and uncertainty, readers cannot judge the magnitude or precision of the comparison. This distinction matters when registry entries are used for evidence synthesis or statistical review.
Finally, the record contains safety counts and a planning illustration description, but neither replaces a full comparative efficacy analysis. Safety counts need context on follow-up and comparative methods, while planning assumptions are not proof of achieved power. The missing results and methods limit what can be learned from the registry record alone.
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 of the posted record is that it does not report the primary endpoint results. Group event counts, comparative estimates, confidence intervals, and p-values are not reported in the registry record. This prevents assessment of the direction, size, and precision of the main comparison, regardless of the randomized design.
The primary endpoint is a composite with several distinct components, but component-specific primary results are not reported in the registry record. The definition is detailed for treated biopsy-proven acute rejection and graft loss, yet no breakdown shows how many participants met each component. Thus, the clinical composition of any overall primary endpoint count cannot be assessed.
Important trial details are also absent. The randomization procedure, allocation ratio, concealment method, baseline characteristics, full CsA target schedules, and masking of outcome assessors are not reported in the registry record. Some arm descriptions are truncated, limiting reconstruction of the complete dosing protocols. The lack of masking is reported, but the consequences for particular assessments cannot be established from the available information.
The analysis plan is not fully described. The registry does not report the planned primary contrast, statistical model, covariate adjustment, multiplicity strategy, original sample-size justification, or details of missing-data handling. Although the intention-to-treat population is named for the primary outcome, procedures for treatment discontinuation, crossover, and incomplete follow-up are not reported in the registry record.
Safety information is presented as counts and selected serious adverse-event terms, without comparative estimates or uncertainty. The term percentages are not attributed to treatment groups in the posted information, and death counts are not reported in the registry record. These gaps restrict interpretation of both efficacy and safety and make the record insufficient for a complete statistical appraisal.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety Study of Everolimus Plus Reduced Cyclosporine Versus Mycophenolic Acid Plus Cyclosporine in Kidney Transplant Recipients — NCT00251004.
- Registry record last updated 2011-05-10; status last verified 2011-04.
- Results first posted 2011-05-10.
- 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.
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18. Record Summary
The registry describes NCT00251004 as a completed, phase 3, randomized, unmasked, parallel-group study sponsored by Novartis. It reports enrollment of 833, a start of 2005-10, and primary completion in 2009-08. The study compared two concentration-controlled everolimus starting-dose regimens with reduced-dose CsA against MPA with standard-dose CsA; all regimens included basiliximab and could include corticosteroids.
The primary endpoint was the number of participants with a composite efficacy failure at 12 months in the intention-to-treat population. The composite included treated biopsy-proven acute rejection, graft loss, death, or loss to follow-up. Secondary outcomes included a graft-loss, death, or loss-to-follow-up composite and a renal-function non-inferiority analysis using calculated glomerular filtration rate.
Primary outcome results and comparative efficacy estimates are not reported in the registry record. Safety counts and selected serious adverse-event terms are listed, but they do not provide a comparative treatment-effect analysis.