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 of Early Versus Delayed Administration of Everolimus in de Novo Renal Transplant Patients (NCT00154297), a randomized phase 4 study. The primary outcome is Number of Participants Considered in Failure for the Primary Failure Endpoint at 3 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00154297 |
| Phase | Phase 4 |
| Condition | Renal Transplantation |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 139 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned de novo kidney transplant recipients described in the official title as being at risk of delayed graft function. The primary endpoint population was the intention-to-treat population. The registry record does not report further eligibility details or participant characteristics that would clarify how closely the enrolled group represents other transplant populations.
Intervention
Participants in the immediate-everolimus arm began oral everolimus within 48 hours of kidney transplantation and continued through the end of the study. The dose was adjusted to maintain a trough level between 3-8 ng/mL.
Comparator
Participants in the delayed-everolimus arm started oral everolimus 4 weeks after transplantation and continued through the end of the study, with dose adjustment to maintain a trough level between 3-8 ng/mL. They received mycophenolic acid until everolimus began.
Primary question
The central question was whether starting everolimus later, rather than within 48 hours, changed the number of participants classified as being in failure for the composite primary endpoint at Month 3. Failure meant that at least one specified event occurred within the first 3 months. The registry record describes this question but does not report the arm-level primary endpoint results or an estimated between-group effect.
3. Trial Design
The registry record identifies this as a randomized, parallel-group, phase 4 study with no masking. It enrolled 139 participants and is listed as completed. The study compared two timings for initiating everolimus after kidney transplantation: initiation within 48 hours or initiation 4 weeks after transplantation. Both groups received everolimus orally twice a day, with doses adjusted to maintain a trough level between 3-8 ng/mL. In the delayed-start group, mycophenolic acid was used until everolimus was initiated.
The stated purpose was to evaluate whether delaying everolimus could reduce associated anti-proliferative complications, such as wound healing disorder, while maintaining efficacy. The primary endpoint was a composite failure measure at Month 3. Secondary outcomes listed in the record cover failure at later follow-up times, dialysis, duration of dialysis, and wound healing disorder. The record does not provide the participant counts for those efficacy outcomes, nor does it report a comparative analysis of them.
Random assignment is intended to make the groups comparable, on average, with respect to factors that could influence outcomes. In an open-label study, participants and study staff know which timing strategy is being used. That knowledge can matter for outcomes involving clinical judgment or reporting, although the registry record does not describe any steps taken to limit such effects. The record does not report the allocation sequence method, concealment procedures, study duration for each participant, or details about follow-up beyond the stated endpoint timeframes. It also does not report a protocol-level explanation for the chosen enrollment size.
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 | Immediate Everolimus | Delayed Everolimus |
|---|---|---|
| STARTED | 65 | 74 |
| COMPLETED | 57 | 67 |
| NOT COMPLETED | 8 | 7 |
Reasons for not completing this period:
| Reason | Immediate Everolimus | Delayed Everolimus |
|---|---|---|
| Death | 5 | 2 |
| Withdrawal by Subject | 0 | 5 |
| Lost to Follow-up | 3 | 0 |
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 | Immediate Everolimus | Delayed Everolimus | Total |
|---|---|---|---|---|
| Participants analysed | 65 | 74 | 139 | |
| Age Continuous | years | 57.3 (SD 10.46) | 58.4 (SD 9.86) | 57.9 (SD 10.13) |
| Sex: Female, Male: Female | Participants | 19 | 20 | 39 |
| Sex: Female, Male: Male | Participants | 46 | 54 | 100 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Considered in Failure for the Primary Failure Endpoint at 3 Months, measured over Month 3.
| 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 considered in failure at Month 3 in the intention-to-treat population. The registry defines failure as the occurrence of at least one specified event within the first 3 months after transplantation. The components are delayed graft function, biopsy-proven acute rejection, graft loss, death, loss to follow-up, and wound healing disorder. Delayed graft function is defined as a need for dialysis within the first 7 days after transplantation, excluding day one. Graft loss is defined as the allograft being presumed lost on the day the patient started and could not be removed from dialysis. Wound healing disorder includes a transplant-related wound being opened beyond 3 weeks, infected, draining fluid, or herniated.
A composite endpoint combines multiple events into one outcome. It can capture a broader range of clinically relevant problems than a single component, and can increase the chance that an event is observed. However, the composite count alone does not show which component occurred or whether components had similar frequency or importance. A participant meeting more than one component is still classified as in failure under the stated definition; the registry record does not describe component-level results for this endpoint.
The registry record describes the endpoint but does not report the number of participants classified as failures in either arm at Month 3. It therefore does not permit a numerical comparison of the primary endpoint between the treatment strategies.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial question and the endpoint definition, but it does not report the primary endpoint counts or a treatment-effect estimate. No arm-level Month 3 failure results, confidence interval, or test result are reported in the registry record. Consequently, the posted information cannot show the direction or magnitude of the primary endpoint comparison, or how precisely any difference was estimated. It is not possible to draw a conclusion about the comparative primary outcome from the record as presented.
The composite endpoint includes delayed graft function, biopsy-proven acute rejection, graft loss, death, loss to follow-up, and wound healing disorder. Those events are not interchangeable. If counts for the composite were available without component results, they would still leave uncertainty about which events contributed to the overall classification. The registry record also does not report the outcome values for the secondary endpoints addressing failure at Month 6 and Month 12, dialysis, dialysis duration, or wound healing disorder. Their inclusion in the outcomes list indicates what the study intended to assess, not what happened in either group.
The safety information does include affected-participant counts. For serious adverse events, the record lists 45 affected participants among 65 at risk in the immediate-everolimus group and 57 among 74 at risk in the delayed-everolimus group. For other adverse events, it lists 64 affected participants among 65 at risk in the immediate group and 70 among 74 at risk in the delayed group. These are descriptive counts; the registry record does not provide an adjusted comparison, uncertainty interval, or statistical test for them. They should not be treated as evidence of a causal difference between strategies on their own.
The record lists serious adverse event terms with percentages, including urinary tract infection and acute renal failure at 9.5%, pyelonephritis and increased blood creatinine at 9.2%, transplant rejection at 8.1%, and complications of transplanted kidney at 7.7%. The record does not provide enough detail in these figures to establish comparative rates by arm or to determine whether a term was experienced by the same participants as another term. Death counts are not reported in the safety information.
Overall, the posted data permit description of the design, endpoint definition, and selected safety counts. They do not support an estimate of the primary treatment effect or a precise comparison of efficacy outcomes. Statistical interpretation must distinguish what the trial planned to measure from outcome results actually reported in the registry record.
9. Statistical Methods Explained
Randomization assigns participants to study groups by chance. In general, its purpose is to reduce systematic differences between groups at the point of assignment, so that later outcome contrasts can be interpreted as comparisons of assigned strategies. Randomization does not ensure that every relevant characteristic is identical between groups, especially in a study of limited size. The registry record says the study was randomized but does not report the sequence-generation or allocation-concealment methods. Those details are not reported in the registry record.
What does the endpoint count?
The primary measure is a count of participants classified as being in failure, rather than a continuous measurement such as a laboratory value. Each participant is classified according to whether at least one component of the composite occurred within the stated window. This kind of outcome can be summarized as the number of people with an event, but comparative interpretation ordinarily also needs the group denominators and an effect estimate with uncertainty. The registry record does not report the primary arm-level counts or such an estimate.
Composite outcomes need careful interpretation because their components may differ in frequency, severity, and clinical meaning. A combined result can obscure whether an apparent group pattern is driven by one component or spread across several. Here the listed components include graft-related events, death, loss to follow-up, and wound healing disorder. The registry record does not report component-specific primary endpoint results, so their respective contributions cannot be assessed.
How should a confidence interval be understood?
In general, a confidence interval describes the range of effect estimates compatible with the observed data under the method used to construct it. It expresses statistical uncertainty; it is not a guarantee that the true effect lies within a particular interval. A narrow interval indicates greater precision than a wide interval, while an interval that spans values in different directions may leave the estimated direction uncertain. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed.
What can a significance test establish?
In general, a significance test evaluates how compatible the data are with a specified null model, conditional on the statistical assumptions. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. A p-value alone would not replace the effect estimate and its uncertainty. No primary endpoint test result or detailed inferential analysis is reported in the registry record.
Why does the analysis population matter?
The primary endpoint is specified for the intention-to-treat population. In general, an intention-to-treat analysis classifies participants according to their randomized assignment, even if their treatment exposure later differs from the assigned strategy. This approach aims to preserve the advantages of randomization and evaluates assignment to a strategy. The registry record does not explain how participants with missing outcomes, treatment changes, or incomplete follow-up were handled in the primary analysis.
Other analysis populations can answer different questions, but their definitions and results are not reported in the registry record. Without a clear account of the analysis population and participant flow, readers cannot determine how all enrolled participants contributed to any outcome analysis. The record also does not report whether outcomes were adjudicated, whether assessors were blinded, or how potential deviations from the assigned timing were handled.
Why is the open-label design relevant?
In general, lack of masking can influence behavior, reporting, clinical decisions, and outcome assessment. This matters most when an endpoint depends partly on judgments or reporting rather than an entirely objective measurement. The study was unmasked, but the registry record does not describe safeguards for outcome assessment or whether endpoint components were reviewed independently. This is a design consideration, not proof that bias occurred.
For binary or count outcomes, statistical methods usually compare the frequency of participants with an event across groups. Methods may use different assumptions about independence, adjustment, or the form of the outcome model. The registry record does not report a statistical analysis plan, a model, covariate adjustments, hypothesis tests, or handling of multiple comparisons. Those methods cannot be reconstructed from the outcome definitions alone.
General sample-size planning asks how many participants would be needed to detect an effect under specified assumptions about the target effect, variability, significance level, power, and allocation. A planning illustration based on an observed effect is not the same as the trial's original sample-size justification, and it is not observed power. The registry record does not report the original sample-size justification or a planned power calculation. Without reported primary outcome estimates, the effect-based planning assumptions cannot be independently interpreted from this record.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary endpoint at Month 3 and secondary outcomes that include the same failure endpoint at Month 6 and Month 12, as well as dialysis-related and wound healing outcomes. When a study evaluates multiple endpoints or time points, repeated testing can raise the chance of at least one apparently notable result occurring by chance. In general, a statistical plan may define a hierarchy or adjustment procedure to address this issue. No multiplicity strategy is reported in the registry record, so it is not possible to determine whether or how the planned comparisons were controlled.
The registry record does not report primary endpoint results or numerical results for the listed secondary outcomes. It also does not describe missing-data methods, imputation, censoring rules, or sensitivity analyses. Loss to follow-up is itself included as a primary composite component, but the record does not explain how that component was distinguished from missing outcome information or how missing information for other components was handled. These omissions limit the ability to assess whether the analysis appropriately accounted for incomplete follow-up.
The primary population is identified as intention-to-treat, but there is no reported participant flow or account of exclusions from outcome analyses. The record therefore does not show how many participants had outcome information available at each time point, or whether all randomized participants were included as intended. Details of the statistical analysis plan and handling of missing data are not reported 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 |
|---|---|---|---|
| Immediate Everolimus | 45 | 65 | 69.2% |
| Delayed Everolimus | 57 | 74 | 77.0% |
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 |
|---|---|
| Immediate Everolimus | 64 of 65 |
| Delayed Everolimus | 70 of 74 |
Most frequent serious adverse event terms
| Event term | Organ system | Immediate Everolimus | Delayed Everolimus |
|---|---|---|---|
| Urinary tract infection | Infections and infestations | 5 of 65 | 7 of 74 |
| Blood creatinine increased | Investigations | 6 of 65 | 5 of 74 |
| Renal failure acute | Renal and urinary disorders | 4 of 65 | 7 of 74 |
| Transplant rejection | Immune system disorders | 3 of 65 | 6 of 74 |
| Pyelonephritis | Infections and infestations | 6 of 65 | 1 of 74 |
| Renal impairment | Renal and urinary disorders | 4 of 65 | 3 of 74 |
| Lymphocele | Vascular disorders | 4 of 65 | 3 of 74 |
| Pyrexia | General disorders | 1 of 65 | 5 of 74 |
| Sepsis | Infections and infestations | 1 of 65 | 5 of 74 |
| Complications of transplanted kidney | Injury, poisoning and procedural complications | 5 of 65 | 1 of 74 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Immediate Everolimus | Delayed Everolimus |
|---|---|---|---|
| Oedema peripheral | General disorders | 26 of 65 | 41 of 74 |
| Anaemia | Blood and lymphatic system disorders | 28 of 65 | 33 of 74 |
| Urinary tract infection | Infections and infestations | 22 of 65 | 25 of 74 |
| Complications of transplanted kidney | Injury, poisoning and procedural complications | 15 of 65 | 19 of 74 |
| Hypertension | Vascular disorders | 15 of 65 | 17 of 74 |
| Dyslipidaemia | Metabolism and nutrition disorders | 12 of 65 | 15 of 74 |
| Constipation | Gastrointestinal disorders | 12 of 65 | 14 of 74 |
| Hypokalaemia | Metabolism and nutrition disorders | 5 of 65 | 13 of 74 |
| Haematoma | Vascular disorders | 6 of 65 | 11 of 74 |
| Lymphocele | Vascular disorders | 9 of 65 | 8 of 74 |
Serious events with the highest arm-level rate: urinary tract infection (9.5%), renal failure acute (9.5%), pyelonephritis (9.2%), blood creatinine increased (9.2%), transplant rejection (8.1%).
The registry record reports serious adverse event counts and counts for other adverse events separately. In the immediate-everolimus group, 45 participants were affected among 65 at risk for serious adverse events, and 64 were affected among 65 at risk for other adverse events. In the delayed-everolimus group, 57 participants were affected among 74 at risk for serious adverse events, and 70 were affected among 74 at risk for other adverse events. These figures count participants identified as affected; they should not be read as numbers of individual adverse event episodes.
The record also lists serious adverse event terms with percentages: urinary tract infection, 9.5%; acute renal failure, 9.5%; pyelonephritis, 9.2%; increased blood creatinine, 9.2%; transplant rejection, 8.1%; and complications of transplanted kidney, 7.7%. The listed terms do not provide an arm-by-arm comparison, and the record does not clarify whether participants could contribute to more than one term. The percentages therefore should not be interpreted as mutually exclusive categories or as a comparative treatment effect.
Death counts are not reported in the registry record. No adjusted safety analysis, uncertainty interval, or test of between-group differences is reported. These safety figures are descriptive and do not establish that one timing strategy caused more or fewer events.
12. What the Result Does, and Does Not, Mean
The trial addresses a specific treatment-timing question: immediate initiation of everolimus compared with initiation 4 weeks after kidney transplantation. The registry record describes a randomized, open-label comparison and specifies a composite primary endpoint at Month 3. That information helps define the question the study set out to examine, but it does not provide the primary outcome counts needed to answer it statistically.
The posted results do not establish whether the immediate or delayed strategy had fewer participants classified as failures. They do not provide a primary effect estimate, a confidence interval, or a test result. As a result, neither the direction nor the precision of the primary comparison can be determined. The absence of a reported estimate should not be mistaken for evidence that the groups were the same.
The composite endpoint also requires caution. A participant could meet the failure definition through any one of several events, including delayed graft function, rejection, graft loss, death, loss to follow-up, or wound healing disorder. Without component-level counts, an overall composite count would not show which events accounted for the result. In this record, even the overall primary counts are not reported.
The adverse-event information is more concrete but remains descriptive. It gives affected-participant counts for serious and other adverse events, along with selected serious-event terms and percentages. It does not offer a comparative analysis or enough detail to identify how the listed terms overlap. These data do not establish a causal safety difference between the two timing strategies.
The trial's stated purpose includes assessing whether delayed administration could reduce anti-proliferative complications while maintaining efficacy. The registry record does not provide the outcome results needed to judge that balance. Any conclusion about efficacy, wound healing, or comparative safety would go beyond the posted results. The appropriate statistical reading is therefore limited: the design and outcome definitions are available, while the principal comparative outcome findings are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly defined endpoint and a reported endpoint result are both needed for statistical interpretation. The registry record describes a composite endpoint with several clinically different components, and specifies an intention-to-treat population. Those features establish what the primary outcome was intended to represent. Without the arm-level counts and an effect estimate, however, a reader cannot assess the observed contrast or its uncertainty.
It also highlights how treatment timing can create a comparison between care strategies rather than simply between a drug and no drug. The delayed-start group received mycophenolic acid until everolimus began, while the immediate group started everolimus within 48 hours. The study's comparison is therefore between the assigned regimens as described, not an isolated assessment of everolimus exposure without other treatment differences.
The open-label design is another useful teaching point. Randomization and masking address different sources of bias: randomization helps balance groups, while masking can limit influences on care, reporting, and assessment after assignment. Here the record states that there was no masking, but does not describe the assessment safeguards. That design feature merits consideration without implying that bias necessarily occurred.
Finally, the record separates outcome definitions from outcome evidence. Listing a primary endpoint, later time points, dialysis outcomes, and wound-healing outcomes does not by itself communicate the results. For a trial to support an interpretable treatment-effect estimate, readers need outcome counts, denominators, an analysis method, and a measure of uncertainty. Those comparative primary results are not reported in the registry record, which limits the statistical conclusions that can be drawn.
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 interpretation is that the registry record does not report the primary endpoint results. No Month 3 failure counts by group, treatment-effect estimate, confidence interval, or statistical test are available. Numerical results for the listed secondary outcomes are also not reported in the registry record. This prevents an assessment of efficacy outcomes and leaves the stated trial question unanswered by the posted results.
The primary endpoint combines events that may differ in frequency and meaning. The record defines its components but does not provide component-level results. It also does not report whether endpoint assessments were adjudicated or whether assessors were masked. Because the trial was unmasked, the absence of information about assessment procedures is relevant when considering outcomes that may involve clinical judgments or reporting.
The record identifies the primary population as intention-to-treat, but does not report participant flow, outcome availability, or the handling of missing information. Loss to follow-up is one component of the composite, while the approach to missing data for other components is not described. The treatment exposure and outcome analysis details needed to evaluate adherence to assigned timing are not reported in the registry record.
Statistical methods are also incompletely described. The registry record does not report the analysis plan, model, adjustment strategy, multiplicity procedure, or sample-size justification. The safety figures are descriptive, without a comparative estimate or uncertainty measure, and deaths are not reported. These limitations do not demonstrate that the study was conducted improperly; they restrict what can be evaluated from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of Early Versus Delayed Administration of Everolimus in de Novo Renal Transplant Patients — NCT00154297.
- Registry record last updated 2011-04-04; status last verified 2011-03.
- Results first posted 2011-01-26.
- 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 record describes a completed, randomized, open-label, parallel-group phase 4 study of immediate versus delayed everolimus in de novo kidney transplant recipients. Enrollment was 139. Immediate treatment began within 48 hours after transplantation; delayed treatment began 4 weeks after transplantation, with mycophenolic acid used until then.
The primary outcome was the number of participants in failure at Month 3 in the intention-to-treat population. The composite included delayed graft function, biopsy-proven acute rejection, graft loss, death, loss to follow-up, and wound healing disorder. The primary outcome counts and comparative analysis are not reported in the registry record. Selected adverse-event counts and serious-event terms are reported, but no comparative safety analysis is given. The record does not report the statistical analysis plan, missing-data methods, multiplicity approach, or sample-size justification.