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 Randomized Trial of Induction Therapies in High Immunological Risk Kidney Transplant Recipients (NCT00782821), a randomized phase 4 study. The primary outcome is Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00782821 |
| Phase | Phase 4 |
| Condition | Kidney Transplantation |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 40 |
| Arms in the primary outcome | 4 |
| Lead sponsor | University of Cincinnati |
| Results posted | Yes |
2. Clinical Question
Population
Kidney transplant recipients described in the registry record as being at high immunological risk. The record lists kidney transplantation as the condition and an enrollment of 40. Further eligibility criteria and participant characteristics are not reported in the registry record.
Intervention
Induction with rabbit antithymocyte globulin (rATG), either alone or in regimens adding rituximab, bortezomib, or both. The record describes a randomized, parallel-group, open-label pilot study.
Comparator
The rATG-only arm is the reference group for the posted comparisons. The additional regimens were rATG with rituximab, rATG with bortezomib, and rATG with both rituximab and bortezomib.
Primary question
At six months, how did the recorded incidence of acute rejection or antibody-mediated rejection compare between each regimen adding a B-cell-modulating agent and rATG alone? The registry defines rejection using Banff criteria. The estimates describe event counts and unadjusted between-arm comparisons; the small arm sizes and uncertainty intervals matter to how they should be read.
The stated research purpose was to examine the effects of adding B lymphocyte modulating agents to an immunosuppressive regimen that included rATG induction, tacrolimus, mycophenolate mofetil, and corticosteroid therapy. The listed interventions include rabbit antithymocyte globulin, Velcade, and Rituxan. The record describes the study as a pilot, but does not report a sample-size justification or a prespecified statistical analysis plan.
The question is comparative, not a test of whether any regimen is effective in general. The posted outcome is a count of participants meeting the rejection definition during the stated timeframe. It does not by itself describe the full clinical course, the severity of every event, or longer-term transplant outcomes. Results for patient and allograft survival at twelve months are listed as secondary outcomes, but results for those outcomes are not posted in the record.
3. Trial Design
The registry describes a phase 4, randomized, parallel-group, open-label pilot study sponsored by the University of Cincinnati. The study status is completed. The recorded start was 2008-09, and primary completion was 2013-02. Enrollment is listed as 40. The four posted arms each have an arm size of 10; the registry does not provide further details about the randomization procedure or allocation concealment.
All four arms included rabbit antithymocyte globulin. The reference arm received rATG alone, described as 1.5mg/kg per dose for six doses on post-operative days 0, 2, 4, 6, 8, and 10. The rATG/rituximab arm is described as five rATG doses and one rituximab dose; rituximab was given on post-operative day 1. The rATG/bortezomib arm is described as five rATG doses and four bortezomib doses. The combination arm included rATG, rituximab, and bortezomib. Its description is truncated in the registry record, so the full timing and dose description for that arm are not reported there.
The trial’s primary endpoint was the incidence of acute rejection or antibody-mediated rejection at six months. Secondary outcomes listed include antibody-mediated rejection and acute cellular rejection at six months, and patient and allograft survival at twelve months. Although five outcome measures are recorded, the registry posts results for the primary outcome and two secondary rejection outcomes; results for the remaining listed outcomes are not reported in the registry record.
Open-label means the record does not describe masking of participants or study personnel. The registry does not report details of who assessed rejection, whether assessors were blinded, the randomization sequence, treatment adherence, or changes in treatment. It also does not report a planned interim analysis or the statistical plan used for the sponsor’s analyses.
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 | Rabbit Antithymocyte Globulin (rATG) | RATG/Rituxan | RATG/Velcade | RATG/Rituxan/Velcade |
|---|---|---|---|---|
| STARTED | 10 | 10 | 10 | 10 |
| COMPLETED | 10 | 10 | 9 | 8 |
| NOT COMPLETED | 0 | 0 | 1 | 2 |
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 | Rabbit Antithymocyte Globulin (RATG) | RATG/Rituxan | RATG/Velcade | RATG/Rituxan/Velcade | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 10 | 10 | 10 | 10 | 40 | |
| Age, Continuous | years | 49.9 (46.3 to 53.8) | 52.8 (45.6 to 62.7) | 50.6 (34.5 to 63.3) | 50.1 (45.3 to 56.9) | 50.9 (34.5 to 63.3) |
| Sex: Female, Male: Female | Participants | 5 | 5 | 8 | 4 | 22 |
| Sex: Female, Male: Male | Participants | 5 | 5 | 2 | 6 | 18 |
| Region of Enrollment: United States | participants | 10 | 10 | 10 | 10 | 40 |
| Pre-transplant diabetes mellitus | participants | 1 | 4 | 3 | 1 | 9 |
| Dialysis pre-transplant | participants | 9 | 7 | 8 | 10 | 34 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection, measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with acute rejection or antibody-mediated rejection by six months. It is a binary outcome at the participant level: a participant either meets the stated endpoint definition during the timeframe or does not. The posted results give the number of participants with an event in each arm, rather than a continuous measure such as a laboratory value or a time-to-event estimate.
The registry describes antibody-mediated rejection as requiring evidence that it is due, at least in part, to anti-donor antibody, using Banff ’97 criteria at six months. Acute rejection is classified by Banff ’97 criteria, updated in 2005. The description includes grades based on findings such as interstitial infiltration, tubulitis, and vascular changes. Those criteria provide a standardized framework for classifying rejection, but the record does not provide participant-level pathology or details of adjudication.
Combining acute rejection and antibody-mediated rejection creates a broad primary endpoint that captures either category. Such a composite can summarize multiple clinically relevant event types in one measure, but its total does not show which component accounts for each event. The registry separately posts counts for antibody-mediated rejection and acute cellular rejection as secondary outcomes, which helps describe components but does not replace the primary comparison.
The endpoint is used to compare the observed frequency of rejection across the randomized regimens during the stated follow-up period. It does not establish the cause of an event or measure outcomes beyond the recorded timeframe. The registry does not report additional endpoint details such as rules for handling multiple episodes in one participant.
7. Results Posted in the Registry
- RATG/Rituxan: 0.0% (0/10) versus 20.0% (2/10) on control; risk difference -20.0 percentage points (95% CI -44.8 to 4.8); unadjusted two-proportion z-test p = 0.136.
- RATG/Velcade: 50.0% (5/10) versus 20.0% (2/10) on control; risk difference 30.0 percentage points (95% CI -9.7 to 69.7), risk ratio 2.50 (0.63–10.00); unadjusted two-proportion z-test p = 0.160.
- RATG/Rituxan/Velcade: 30.0% (3/10) versus 20.0% (2/10) on control; risk difference 10.0 percentage points (95% CI -27.7 to 47.7), risk ratio 1.50 (0.32–7.14); unadjusted two-proportion z-test p = 0.606.
Risk difference: RATG/Rituxan
95% CI: -44.8 to 4.8 percentage points
Recalculated from the posted summary statistics
8. Secondary Efficacy Endpoints
The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.
| Secondary outcome | Type | Effect measure | Estimate (95% CI) | Planning size, 80% power |
|---|---|---|---|---|
| Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005) | Binary Endpoint | Risk difference | -10.0 pts (-28.6 to 8.6) | n/a |
| Acute Cellular Rejection by Banff '97 Criteria (Updated 2005) | Binary Endpoint | Risk difference | -10.0 pts (-28.6 to 8.6) | n/a |
Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005)
- Endpoint type: Binary: the number of participants with the event, compared as proportions.
- Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
- Result:
- RATG/Rituxan: 0.0% (0/10) versus 10.0% (1/10) on control; risk difference -10.0 percentage points (95% CI -28.6 to 8.6); unadjusted two-proportion z-test p = 0.305.
- RATG/Velcade: 30.0% (3/10) versus 10.0% (1/10) on control; risk difference 20.0 percentage points (95% CI -13.9 to 53.9), risk ratio 3.00 (0.37–24.17); unadjusted two-proportion z-test p = 0.264.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between RATG/Rituxan and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between RATG/Velcade and the control. The interval gives the range of effects that remain compatible with the data.
Acute Cellular Rejection by Banff '97 Criteria (Updated 2005)
- Endpoint type: Binary: the number of participants with the event, compared as proportions.
- Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
- Result:
- RATG/Rituxan: 0.0% (0/10) versus 10.0% (1/10) on control; risk difference -10.0 percentage points (95% CI -28.6 to 8.6); unadjusted two-proportion z-test p = 0.305.
- RATG/Velcade: 10.0% (1/10) versus 10.0% (1/10) on control; risk difference 0.0 percentage points (95% CI -26.3 to 26.3), risk ratio 1.00 (0.07–13.87); unadjusted two-proportion z-test p = 1.000.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between RATG/Rituxan and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between RATG/Velcade and the control. The interval gives the range of effects that remain compatible with the data.
The registry lists secondary outcomes for antibody-mediated rejection and acute cellular rejection at six months, as well as patient and allograft survival at twelve months. Results are posted for the two rejection outcomes, but not for the survival outcomes. Across the posted rejection endpoints, the pattern remains one of sparse events and imprecise comparisons. The counts do not provide a clear, consistent basis for distinguishing the additional regimens from rATG alone.
These component outcomes help place the combined primary endpoint in context, because the primary result groups acute and antibody-mediated rejection together. However, component findings are themselves based on limited counts, and they do not independently resolve the uncertainty in the primary comparison. The registry does not report analyses designed to establish whether one component is more important than another or whether the component pattern is consistent across participants.
Secondary results generally carry less weight than a prespecified primary result because they may be examined after the main outcome and can involve additional comparisons. Each unadjusted comparison adds another opportunity for a chance pattern to appear. Without a reported multiplicity plan, a secondary p value should not be read as confirmatory evidence. The record also does not report whether these secondary analyses were prespecified, how missing outcomes were handled, or whether an analysis hierarchy was used.
The posted secondary findings are best treated as descriptive context for the primary endpoint, not as separate proof for or against a regimen. The survival outcomes are listed but have no results in the registry record. Their absence means the record cannot support a statistical interpretation of survival differences at the stated follow-up. Taken together, the secondary information does not remove the uncertainty evident in the primary comparison.
Secondary outcomes registered for this trial, for reference (only those above were recalculated):
- Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005)
- Acute Cellular Rejection by Banff '97 Criteria (Updated 2005)
- Patient Survival at 12 Months
- Patient Allograft Survival at 12 Months
9. Statistical Interpretation
In the rATG-only arm, 2 of 10 participants were recorded as having the primary endpoint by six months. The corresponding counts were 0 of 10 with rATG/rituximab, 5 of 10 with rATG/bortezomib, and 3 of 10 with rATG/rituximab/bortezomib. These are observed counts in a small pilot study, not precise estimates of what would occur in a broader population.
The posted risk difference for rATG/rituximab versus rATG alone is -0.2, with an unadjusted p value of 0.136. The interval around this estimate extends from a reduction to a possible increase, so the zero difference is compatible with the posted interval. For rATG/bortezomib, the risk difference is 0.3 and the unadjusted p value is 0.16. Its interval also includes zero and allows effects in either direction. For the combination regimen, the risk difference is 0.1 and the unadjusted p value is 0.606; its interval likewise includes zero. These comparisons do not establish a difference between any added-agent regimen and rATG alone.
The point estimates are not all in the same direction: the rituximab-alone addition has a negative risk difference, while the bortezomib-containing comparisons have positive point estimates. With only 10 participants per arm, each observed event changes the count appreciably. The resulting estimates are therefore especially sensitive to the outcomes of individual participants. The confidence intervals reinforce that the data do not pin down the size or direction of the underlying differences with precision.
The unadjusted p values should not be treated as proof that regimens are equivalent, nor as evidence that one is better. A non-small p value does not show that the true difference is zero. Conversely, the observed differences alone do not establish a treatment effect. The registry record does not report whether the comparisons were part of a prespecified analysis or whether any adjustment for multiple comparisons was planned.
The record lists an overall enrollment of 40, but the outcome comparisons are between arms with 10 participants each. The posted evidence is therefore best read as descriptive and exploratory. It gives a preliminary account of event frequencies under the studied regimens; it cannot by itself support a definitive comparative conclusion.
10. Statistical Methods Explained
The primary outcome is binary because it records whether each participant had acute rejection or antibody-mediated rejection during the six-month timeframe. For a binary endpoint, a basic description is the number with an event out of the number assessed in each group. The posted counts are 2 of 10 for rATG alone, 0 of 10 for rATG/rituximab, 5 of 10 for rATG/bortezomib, and 3 of 10 for the combination regimen. These counts describe the participants represented in the registry results; they are not, on their own, a forecast of event rates in other settings.
The comparisons use a risk difference: the event proportion in an added-agent arm minus the event proportion in the rATG-only reference arm. A negative value means the observed event proportion was lower in the added-agent arm, while a positive value means it was higher. This is a direct measure on the scale of a difference in proportions. It does not express a relative change, and it should be interpreted alongside the arm counts and the uncertainty interval.
A confidence interval describes a range of values compatible with the data and the method used to calculate the interval. It is not a guarantee that the true effect lies within that range, nor is it a range of participant outcomes. When the interval includes zero for a risk difference, the data are compatible with no difference as well as with effects on either side of zero. Wider intervals indicate less precise estimates. With small binary-outcome groups, uncertainty can be substantial, particularly when event counts are low.
The posted p values are unadjusted. A p value measures how incompatible the observed data are with a specified null model of no difference, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of a difference. An unadjusted p value also does not account for testing multiple comparisons or endpoints. The registry record does not report the test procedure, a prespecified significance threshold, or a multiplicity strategy; no further analysis plan should be inferred from these values.
Random allocation can help balance measured and unmeasured characteristics across study arms on average, but it does not ensure balance in a small trial. The record identifies the trial as randomized, but details of sequence generation and concealment are not reported in the registry record. The trial is open-label, so masking is not reported as part of its design. Whether outcome assessors were masked is not reported in the registry record either. These design details can affect confidence in how outcomes were assessed and how comparisons should be interpreted.
The posted planning illustrations use the observed effect as a starting point and describe participants per arm for 80% power or 90% power under specified assumptions. They are planning calculations, not observed power and not evidence that the pilot was adequately powered. For the primary comparison with rATG/bortezomib, the illustrations give 39 participants per arm for 80% power and 52 for 90% power when planning for 100% of the observed effect; for 75% of the observed effect, they give 66 and 88; for 50% of the observed effect, they give 138 and 185. For the primary comparison with the combination regimen, the corresponding illustrations are 294 and 392 for 100% of the observed effect, 505 and 675 for 75%, and 1,094 and 1,464 for 50%. These are conditional illustrations under a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The record does not report that these assumptions were the trial’s own design assumptions.
Because planning calculations start from observed effects, they inherit the uncertainty of a small pilot estimate. An observed difference can be unstable, and an illustration based on a fraction of that estimate is not a guarantee of a future study’s power or result. The registry does not report a sample-size justification used before enrollment. The calculations therefore help illustrate how design requirements depend on the effect targeted, but they should not be mistaken for the original trial’s rationale or a conclusion about its ability to detect an effect.
General statistical principle: when a study examines multiple groups and outcomes, the chance of at least one apparently unusual result can increase if each comparison is considered independently without adjustment. An adjustment can change the interpretation of p values, but which method is appropriate depends on the analysis plan and scientific aims. Since the registry record does not report a multiplicity plan, the posted unadjusted comparisons should be regarded as exploratory rather than as a family of controlled confirmatory tests.
There are no sponsor-reported analyses listed in the registry record for the posted outcomes. The record therefore does not give a detailed account of model adjustment, analysis population, handling of missing observations, or sensitivity analyses. The displayed comparisons should be interpreted as the unadjusted comparisons represented by their reported estimates, not as evidence of an unreported adjusted model.
11. Confidence Intervals and Precision
Precision is limited by the small arm sizes and the low event counts. For the primary endpoint, the observed counts range from 0 of 10 to 5 of 10 across the four groups. A small change in the number of participants with an event would shift the observed proportion noticeably. That makes the point estimates vulnerable to random variation and limits how confidently they can be generalized beyond the trial participants.
The risk-difference intervals for all three comparisons include zero. This means the posted data do not rule out no difference, and they remain compatible with effects in both directions. The intervals are broad relative to the point estimates, particularly for comparisons where the observed arm counts differ. Their breadth is a direct warning against reading the point estimate as a precise estimate of the true comparative effect.
Confidence intervals and p values answer related but distinct questions. The interval communicates uncertainty about the effect size on the risk-difference scale; the p value summarizes compatibility with a null model under a testing procedure. Neither measure tells whether a difference is clinically important. The registry record does not provide a clinically important threshold for the primary endpoint, so the clinical meaning of a particular risk difference cannot be determined from these results alone.
The absence of reported sponsor analyses also limits what can be assessed about precision. The registry does not report adjusted estimates, methods for missing outcomes, or sensitivity analyses. No statement about the robustness of these estimates to alternative methods is supported by the record. Overall, the estimates are useful for describing the pilot’s observed outcomes, but their uncertainty is too large for fine distinctions among the regimens.
12. Multiplicity, Missing Data and Analysis Populations
The registry record lists several outcomes and multiple arm comparisons, but it does not report a plan for controlling multiplicity. This matters because repeated testing can increase the chance of at least one apparently notable result when there is no true difference. The posted p values are unadjusted, and there is no reported correction or testing hierarchy. They should therefore be interpreted as exploratory evidence rather than as a set of confirmatory tests with a known overall error rate.
Missing-data handling is not reported in the registry record. The posted outcome counts give the arm sizes used for the comparisons, but the record does not explain whether every randomized participant was assessed, whether any outcomes were unavailable, or how unavailable results would have been handled. It also does not identify an intention-to-treat or per-protocol analysis population. Without these details, it is not possible to assess whether the reported outcome counts reflect all randomized participants or a particular analysis subset.
The registry lists no sponsor-reported analyses for these results. Details such as covariate adjustment, sensitivity analyses, outcome adjudication, and the statistical tests used are not reported in the registry record. The randomized design is stated, but the record does not describe the allocation sequence or concealment. These omissions limit assessment of the analysis process; they do not establish that a particular procedure was or was not used outside what the registry reports.
The registry also lists patient survival and allograft survival at twelve months, but results for these outcomes are not reported in the registry record. The record does not explain why those results are absent. Consequently, no conclusion about those outcomes or about the completeness of their follow-up is supported. The listed five outcome measures should not be taken to mean that all were reported with results.
13. 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 |
|---|---|---|---|
| Rabbit Antithymocyte Globulin (RATG) | 2 | 10 | 20.0% |
| RATG/Rituxan | 4 | 10 | 40.0% |
| RATG/Velcade | 4 | 10 | 40.0% |
| RATG/Rituxan/Velcade | 2 | 10 | 20.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Rabbit Antithymocyte Globulin (RATG) | 10 of 10 |
| RATG/Rituxan | 10 of 10 |
| RATG/Velcade | 10 of 10 |
| RATG/Rituxan/Velcade | 10 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Rabbit Antithymocyte Globulin (RATG) | RATG/Rituxan | RATG/Velcade | RATG/Rituxan/Velcade |
|---|---|---|---|---|---|
| CMV Viremia | Infections and infestations | 1 of 10 | 3 of 10 | 4 of 10 | 2 of 10 |
| Other Infections | Infections and infestations | 2 of 10 | 4 of 10 | 4 of 10 | 0 of 10 |
| BKV Viremia | Infections and infestations | 0 of 10 | 2 of 10 | 3 of 10 | 2 of 10 |
| CMV Invasive Disease | Infections and infestations | 0 of 10 | 0 of 10 | 1 of 10 | 2 of 10 |
| CMV +/- Status | Infections and infestations | 1 of 10 | 0 of 10 | 0 of 10 | 1 of 10 |
| BKV Nephropathy | Infections and infestations | 0 of 10 | 1 of 10 | 1 of 10 | 0 of 10 |
| EBV Viremia | Infections and infestations | 0 of 10 | 0 of 10 | 1 of 10 | 0 of 10 |
| EBV +/- Status | Infections and infestations | 0 of 10 | 0 of 10 | 0 of 10 | 0 of 10 |
| EBV-related disease / PTLD | Infections and infestations | 0 of 10 | 0 of 10 | 0 of 10 | 0 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rabbit Antithymocyte Globulin (RATG) | RATG/Rituxan | RATG/Velcade | RATG/Rituxan/Velcade |
|---|---|---|---|---|---|
| CTCAE Grade 1 Nausea/Vomiting | Gastrointestinal disorders | 3 of 10 | 6 of 10 | 2 of 10 | 3 of 10 |
| CTCAE Grade 1 Diarrhea | Gastrointestinal disorders | 2 of 10 | 3 of 10 | 3 of 10 | 5 of 10 |
| CTCAE Grade 2 Diarrhea | Gastrointestinal disorders | 2 of 10 | 3 of 10 | 3 of 10 | 3 of 10 |
| CTCAE Grade 2 Nausea/Vomiting | Gastrointestinal disorders | 0 of 10 | 0 of 10 | 3 of 10 | 3 of 10 |
| CTCAE Grade 3 Nausea/Vomiting | Gastrointestinal disorders | 3 of 10 | 1 of 10 | 1 of 10 | 1 of 10 |
| CTCAE Grade 3 Diarrhea | Gastrointestinal disorders | 0 of 10 | 1 of 10 | 2 of 10 | 1 of 10 |
Serious events with the highest arm-level rate: cmv viremia (40.0%), other infections (40.0%), bkv viremia (30.0%), cmv invasive disease (20.0%), cmv +/- status (10.0%).
For serious adverse events, the registry records 2 affected participants in the rATG-only group, 4 in the rATG/rituximab group, 4 in the rATG/bortezomib group, and 2 in the combination group. Each group has 10 participants at risk in the posted safety results. These figures describe the recorded counts; they do not establish that differences between groups are caused by a regimen.
The most frequently listed serious-event terms are CMV viremia and other infections, each reported as 40.0%; BKV viremia, reported as 30.0%; CMV invasive disease, reported as 20.0%; and CMV +/- status and EBV viremia, each reported as 10.0%. The registry record does not clarify the denominator or counting convention for these term percentages, so they should not be interpreted as arm-specific rates or added together.
Other adverse events are recorded for 10 participants in each group. Death counts are not reported in the registry record. These safety entries do not provide event timing, severity grading beyond the serious/non-serious categorization, duration, attribution, or exposure-adjusted rates. They therefore support a description of what was posted, not a complete comparative safety assessment.
14. What the Result Does, and Does Not, Mean
The primary result describes the number of participants meeting the registry’s rejection definition by six months in each randomized arm. It shows that the observed counts differed across the small groups, with fewer events in the rATG/rituximab arm and more in the bortezomib-containing arms than in the rATG-only arm. The accompanying intervals are broad and include no difference, so the results do not establish a reliable direction or size of comparative effect.
These data do not show that an added-agent regimen works or does not work. They also do not show that the regimens are equivalent. Lack of a statistically clear difference is not proof that effects are the same; it can also reflect limited information. Conversely, a point estimate favoring or disfavoring an arm is not sufficient evidence of a treatment effect, particularly in a small pilot with sparse events.
The results concern the registry-defined endpoint and timeframe, not every outcome relevant to transplantation. They do not establish longer-term effects on patient survival or allograft survival, for which results are not reported in the registry record. Nor do the rejection counts by themselves characterize event severity, recurrence, or the overall balance of benefits and harms. Safety counts offer additional descriptive information but do not provide a complete comparative safety analysis.
General statistical principle: a randomized comparison is informative when its design and conduct are sound, outcomes are adequately observed, and estimates are sufficiently precise for the question. The registry reports randomization but leaves important analytic and operational details unreported. For that reason, these posted results are most appropriately understood as preliminary comparative observations from a pilot study, rather than as a definitive basis for selecting a regimen.
15. Why This Trial Matters Statistically
This trial illustrates how a randomized study can produce an interpretable comparative estimate while still leaving substantial uncertainty. The risk difference communicates the observed contrast in a direct way, and the confidence intervals show that the estimates remain compatible with a range of possible effects. Reading the counts, point estimates, and intervals together is more informative than focusing on a single p value.
The pilot also demonstrates why small event counts matter. With 10 participants in each arm, a limited number of outcomes can strongly influence the observed pattern. The apparent direction of an estimate should not be confused with a stable underlying difference. This is particularly relevant when several added-agent regimens and more than one rejection outcome are examined.
The planning illustrations offer a statistical lesson as well: projected sample requirements depend on the effect selected for detection. A calculation based on the full observed effect can differ substantially from one based on a smaller fraction. Because the observed effect in a pilot is uncertain, those projections are useful as conditional planning examples, not as evidence of realized power or as a claim about the original design.
Finally, the record shows the importance of transparent reporting. A registry entry that includes arm counts and outcome definitions supports basic interpretation, while the absence of analysis plans, missing-data procedures, and results for listed survival outcomes limits broader assessment. The distinction between reported details and unreported details is essential to responsible statistical reading.
16. 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.
Several limitations are specific to the information in this registry record. The study is described as a pilot, and each arm has 10 participants. The small groups and low event counts lead to imprecise estimates, as reflected by intervals that include zero. The record does not report a sample-size justification, so the intended precision or target effect cannot be established.
The trial is open-label. The record does not say whether rejection assessment or outcome adjudication was masked, and details of randomization sequence generation and allocation concealment are not reported. The entry gives regimen descriptions, but the description for the combined rATG/rituximab/Velcade arm is truncated. Full details of its dosing schedule are therefore not reported in the registry record.
There are no sponsor-reported analyses listed. The registry does not report the prespecified statistical plan, analysis population, missing-data methods, multiplicity approach, or sensitivity analyses. These omissions prevent assessment of whether the posted comparisons match a planned analysis or how robust they are to analytic choices. Results for listed patient and allograft survival outcomes are also not reported in the registry record.
Finally, the primary outcome combines acute rejection and antibody-mediated rejection. Separate secondary counts provide some component information, but the record does not describe event-level details, recurrence rules, or adjudication procedures. The listed safety information lacks details about event timing, attribution, and the denominator for serious-event term percentages. These limitations restrict the conclusions that can be drawn from the posted results without implying that unreported procedures were necessarily absent from the study.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: Randomized Trial of Induction Therapies in High Immunological Risk Kidney Transplant Recipients — NCT00782821.
- Registry record last updated 2016-01-20; status last verified 2015-12.
- Results first posted 2016-01-20.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
20. Record Summary
The record describes a completed phase 4, randomized, parallel-group, open-label pilot study of induction regimens for high immunological risk kidney transplant recipients. Enrollment is listed as 40, with four arms of 10 participants each: rATG alone, rATG with rituximab, rATG with bortezomib, and rATG with both agents. The primary endpoint was acute or antibody-mediated rejection by six months.
Observed primary-event counts ranged from 0 of 10 to 5 of 10. All three posted unadjusted risk-difference intervals include zero, and no sponsor-reported analyses are listed. Results are posted for two secondary rejection outcomes; results for listed twelve-month survival outcomes are not reported in the registry record. The small groups, broad uncertainty, and unreported analysis details make the findings descriptive and exploratory rather than definitive.