"A Pilot Study to Determine the Safety of Campath-1H (Anti-CD52) Therapy in Primary Renal Allograft Transplantation": Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for "A Pilot Study to Determine the Safety of Campath-1H (Anti-CD52) Therapy in Primary Renal Allograft Transplantation" (NCT00365846), a na phase 2 study. The primary outcome is Incidence of Allograft Rejection.

2. Clinical Question

The registry record identifies a safety-focused pilot in renal transplantation, with additional listed outcomes concerning severe allograft rejection, survival, infection, malignancies, and kidney allograft survival. These outcomes place rejection and safety within a broader assessment of transplant follow-up, but their presence in the record does not establish that results were reported for them. The record lists 29 participants as enrolled. Because the study has no control arm, any outcome observed in this group would describe participants treated under this study approach; it would not by itself show what would have happened under a different approach. The record does not report a treatment-effect estimate or comparative statistical test.

3. Trial Design

This is a completed Phase 2 study with a single-group model and no masking. Allocation is recorded as NA. The record names the group as Campath 1H induction with sirolimus immunosuppression. Its description places Campath-1H at day -1 and day 0 of kidney transplantation and then describes long-term, CNI-free immunosuppressive therapy with sirolimus. No separate control group is listed, so this is not a randomized comparison or a like-for-like control comparison.

The registry lists enrollment of 29 and identifies renal transplant as the condition. The study start is recorded as 2000-08, primary completion as 2005-07, and status as completed. The sponsor is University of Wisconsin, Madison. These record fields describe the study’s registration and timeline, but they do not establish how many participants contributed data to each outcome. Outcome-specific analysis populations, follow-up completeness, and reasons for any difference between enrollment and the adverse-event population are not reported in the registry record.

The primary endpoint is incidence of allograft rejection, expressed as the number of participants and assessed over 3 years. Listed secondary outcomes include severe allograft rejection, defined in the record as >Banff 2A or requiring antibody treatment; patient survival; post-transplant infection; malignancies; and kidney allograft survival. The record lists 6 outcome measures but no analyses. That distinction matters: outcome names identify what the study intended to assess, while the analyses and their results would show how those outcomes were actually evaluated and what was observed. Those analysis details are not reported in the registry record.

The study summary describes two aims: examining use of Campath-1H to prevent rejection in first-time renal transplant subjects and reducing the overall daily amount of anti-rejection medications. The posted record does not state a comparative design for assessing medication reduction, nor does it provide a numerical medication-use result. Since the study has one group, the design can describe outcomes under the regimen but cannot isolate a causal difference from another regimen. The registry record does not report further protocol details, such as eligibility criteria, treatment adherence procedures, or the statistical plan.

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

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Allograft Rejection, measured over 3 years.

The primary endpoint is the incidence of allograft rejection, recorded as a number of participants and assigned a 3 years timeframe. In general, an incidence endpoint describes how many people in a defined group experience an event during a specified period. Rejection is clinically relevant to the study’s stated purpose because the summary identifies prevention of rejection as a central question in primary renal transplantation. A participant-based count is also directly interpretable: it concerns people with an event, rather than the total number of episodes, unless the endpoint definition specifies otherwise.

The registry record does not provide a fuller operational definition for the primary endpoint. It does not state how rejection was diagnosed, whether repeat events in a participant were counted, or how incomplete follow-up was handled. The listed definition of severe allograft rejection is a secondary outcome definition and should not be assumed to define the broader primary endpoint. The record also does not report the observed primary-endpoint count, a rate, an estimate of uncertainty, or an analysis result. Thus the endpoint’s name and timeframe can be described, but the frequency of rejection in the study cannot be inferred from this record.

In general, a prespecified endpoint helps focus a study on a defined outcome rather than selecting a result after observing the data. Its usefulness for interpretation depends on clear definitions, complete outcome ascertainment, and transparent reporting of the analysis population. Those details are not reported in the registry record. The primary endpoint also does not, by itself, answer the medication-reduction aim in the study summary; that would require a reported medication-use measure and a clear basis for interpreting it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with distinguishing the study question from the design used to address it. This record describes a single-group Phase 2 pilot with no masking and allocation recorded as NA. The intervention group received Campath-1H induction followed by sirolimus immunosuppression, according to the arm description. Because no concurrent control group is listed, the study can report outcomes among participants treated under this regimen, but it cannot directly estimate a contrast against another strategy. General statistical principle: a comparison requires outcome information from groups whose contrast is defined by the design or analysis. A one-group outcome count is not itself a comparative treatment effect.

What does a participant count represent?

The primary endpoint is specified as the number of participants with allograft rejection over 3 years. For a binary outcome, each participant is classified according to whether the defined event occurred during the stated period. A count is the number classified as having the event; an event proportion would additionally relate that count to the relevant analysis population. The registry record does not give the primary count or identify the analysis denominator. It also does not report whether the analysis used a particular event definition, how follow-up time was handled, or how participants with incomplete endpoint information were treated. No rate or proportion should therefore be reconstructed from the other record fields.

The adverse-event entries use at-risk and affected counts for Group 1. In general, an at-risk denominator identifies the participants included in the corresponding safety accounting, while the affected count identifies participants recorded with an event. Here, 28 are listed at risk for serious events and 19 affected; for other events, 28 are listed at risk and 28 affected. These safety figures do not supply the missing primary-endpoint result. The registry record does not explain why the at-risk group differs from the enrollment entry, so the reason should not be inferred.

Why does uncertainty matter?

A point estimate, such as an event count or proportion, describes the observed data but does not convey how much uncertainty surrounds an estimate of the underlying event frequency. In general, a confidence interval gives a range of values compatible with the data under a specified statistical method and its assumptions. Its width reflects both the amount of information and variability. It is not reported for the primary endpoint in the registry record, so the precision of any primary estimate cannot be judged. A missing interval is not evidence that the estimate is precise, imprecise, or statistically significant.

Likewise, a p-value is a measure calculated under a statistical model and a null hypothesis; it does not state the probability that a treatment works or that a finding is due to chance. No primary-endpoint p-value or analysis is reported in the registry record. General statistical interpretation should therefore stop short of significance claims. The record lists 0 analyses, which means a reader cannot use it to identify a posted analysis result, adjustment, or model for the listed outcomes.

What does the planning illustration mean?

The planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. In general, planning calculations ask what sample size might be needed under chosen assumptions to detect a target effect with a chosen operating characteristic. They are conditional on those assumptions; they do not demonstrate that a study actually had a particular probability of detecting an effect after it was conducted. In particular, sample-size illustrations are not observed power.

Those assumptions should not be mistaken for the design of this trial. The registry record describes a single group and no randomized comparison. It does not report the original sample-size justification, an interim-analysis plan, or the prespecified statistical analysis plan. Nor does the posted primary result provide an observed effect to assess in this explanatory text. The planning assumptions can only be understood as hypothetical illustrations, not a reconstruction of the study protocol.

How should outcome definitions be kept separate?

The primary outcome is allograft rejection, while the listed secondary outcome of severe allograft rejection has its own threshold: >Banff 2A or requiring antibody treatment. The serious adverse-event list includes Acute kidney graft rejection, but a safety-event term is not automatically interchangeable with either outcome definition. Definitions, reporting rules, and analysis populations may differ. In general, combining results with different definitions can mislead, even when the labels sound similar. The registry record does not report enough detail to determine whether these measures overlap or how they were adjudicated.

Multiplicity is another general consideration when a study reports several outcomes or analyses. Testing many hypotheses can increase the chance of a nominally notable result arising by chance if no plan addresses the family of tests. The registry record lists multiple secondary outcomes but does not report an analysis plan, adjustment approach, or which analyses were performed. It is therefore not possible to determine whether multiplicity was considered or how it would affect interpretation.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Group 1")
n      <- c(28)
events <- c(13)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Group 1  28  13  46.4  27.5  66.1  29.5  64.2  29.4  64.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary endpoint and 6 outcome measures, including secondary outcomes for severe allograft rejection, patient survival, post-transplant infection, malignancies, and kidney allograft survival. It reports 0 analyses. This leaves no posted analysis results with which to assess outcome-specific estimates, statistical tests, or the relationship between planned and reported outcomes.

In general, multiplicity matters when researchers evaluate several outcomes or perform several statistical tests. Without an analysis plan, readers cannot determine which outcomes were primary for inference, whether tests were adjusted, or whether the reported emphasis reflects prespecified priorities. The registry record does not report a multiplicity strategy, so no claim about adjustment or its absence should be made.

Missing-data handling and analysis populations are also not reported in the registry record. The enrollment entry is 29, while the safety entries list 28 participants at risk. The record does not explain this difference, describe outcome-specific denominators, or state whether all enrolled participants were included in each analysis. It also does not describe loss to follow-up, missing endpoint measurements, exclusions, or the approach used for incomplete data. These gaps limit assessment of completeness and possible bias.

General principle: missing outcomes can affect interpretation when the probability of missingness is related to participants’ health or outcomes. The direction and size of any such effect cannot be inferred without information about the missingness and analysis. The record does not report enough information to evaluate that issue. It also does not report an analysis population definition or a statistical plan for the primary endpoint.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute kidney graft rejection (46.4%), urinary tract infection (35.7%), abdominal hernia (25.0%), herpes simplex (17.9%), pneumonia (17.9%).

The safety record lists Group 1 with 28 participants at risk for serious adverse events and 19 affected. For other adverse events, it lists 28 at risk and 28 affected. The record names the most frequent serious-event terms as Acute kidney graft rejection at 46.4%, Urinary tract infection at 35.7%, abdominal hernia at 25.0%, Herpes simplex at 17.9%, Pneumonia at 17.9%, and Herpes Zoster at 10.7%. These are the reported safety figures and terms; they should be read as registry entries, not as comparative estimates.

In general, adverse-event percentages describe the reporting group and depend on the event definitions, follow-up, and reporting process. They do not by themselves establish that the intervention caused an event. This study has no comparator group, and the record does not report a causal safety analysis or detailed event-ascertainment methods. The at-risk counts are safety denominators, not necessarily the denominator for the primary rejection endpoint. The serious-event term Acute kidney graft rejection also should not be treated as the primary endpoint result, because the registry record does not establish that the definitions or counting methods match.

The record does not report event timing, severity grading beyond the serious-event designation, resolution, or participant-level overlap among event terms. A participant may have more than one event term, so the listed percentages should not be added or treated as mutually exclusive categories. Safety results describe events recorded during the study; they do not alone establish an overall benefit-risk balance.

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

The record establishes that a completed Phase 2 pilot studied Campath-1H induction followed by sirolimus immunosuppression in primary renal transplantation. It records enrollment of 29, a single-group design, no masking, and an intended primary endpoint of allograft rejection over 3 years. It also records selected safety counts and serious-event terms. These registry entries describe the study and some posted safety information, but they do not provide the primary rejection result.

The result does not establish whether rejection was prevented, whether the amount of daily anti-rejection medication was reduced, or whether the regimen was better or worse than an alternative. The study summary names those aims, but the registry record does not report a numerical medication-use outcome or a controlled comparison. The absence of a posted primary result should not be interpreted as evidence that no rejection occurred, nor as evidence that rejection was frequent.

Because there is no comparator group, the record cannot isolate treatment effects from other influences on outcomes. General statistical principle: outcomes observed in a treated group can describe that group, but attribution of differences to treatment ordinarily requires a defensible comparison and assumptions appropriate to the design. This record does not support a comparative conclusion. It also does not provide a primary-endpoint estimate with an interval, so precision cannot be judged.

The safety counts and percentages can be read as reported observations for the recorded group. They are not proof that the intervention caused each event, and they do not supply a complete assessment of safety. The record lacks detailed information about event timing, definitions, completeness, and analysis. Likewise, listing survival, infection, malignancy, and severe rejection as secondary outcomes does not establish what those outcomes showed.

The appropriate interpretation is therefore limited: the registry documents a completed, single-group pilot and records certain safety figures, while the primary endpoint and other outcome results are not reported in the registry record. This supports a description of the research question and reporting gaps, not a claim that the treatment works or does not work.

14. Why This Trial Matters Statistically

This study is statistically instructive because its clinical question and its design do not have the same scope. The summary asks whether Campath-1H can prevent rejection and reduce daily anti-rejection medication, while the record describes a single group with no comparator. A single-group pilot can document what was observed among participants receiving the regimen, but it cannot directly show how those outcomes compare with another approach. The design therefore sets a boundary on interpretation before any numerical result is considered.

The registry also illustrates why endpoint reporting matters. It identifies allograft rejection as the primary endpoint and gives a 3 years timeframe, but does not report a primary result or analysis. Without the event count, analysis denominator, uncertainty, and endpoint details, readers cannot estimate the observed rejection frequency or judge its precision. An endpoint label alone is not a result.

The safety entries further demonstrate the importance of keeping related measures distinct. Acute kidney graft rejection appears among serious adverse-event terms, while allograft rejection is the named primary endpoint and severe rejection has a separate definition. Similar wording does not guarantee identical definitions or counting rules. Careful interpretation avoids treating these entries as interchangeable.

Finally, the planning assumptions illustrate how a calculation can be useful without describing the actual trial design. The stated planning illustration uses two arms and equal allocation, whereas this study is recorded as single-group. That contrast is a reminder that hypothetical planning results should not be read as observed power or as evidence about the study’s original design. The registry record does not report the original sample-size rationale or full statistical plan. Transparent reporting of those details, along with outcome results and missing-data handling, is needed for readers to evaluate how reliably a pilot’s observations answer its research question.

15. 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 principal limitation for interpreting this specific record is that no numerical primary-endpoint result is reported. The primary outcome is named as incidence of allograft rejection over 3 years, but there is no posted count, denominator, estimate, confidence interval, or analysis. The record therefore cannot establish the observed rejection frequency or its precision.

The single-group, unmasked design has no concurrent comparator. This prevents a direct comparison with another immunosuppressive strategy and limits causal interpretation of any observed outcome. Allocation is recorded as NA, and no control arm is described. The study is identified as a pilot, but the registry record does not report the original sample-size justification or the statistical plan.

Other design and reporting details needed for a fuller assessment are not reported in the registry record. These include detailed eligibility criteria and participant characteristics, the primary rejection definition and ascertainment process, outcome-specific analysis populations, follow-up completeness, and handling of missing data. The record does not explain why the safety entries list 28 participants at risk while enrollment is 29.

The listed secondary outcomes and adverse-event terms do not resolve these gaps. The record does not report numerical results for the listed secondary outcomes or analyses, and it does not describe whether multiple outcomes were adjusted for or prioritized in an analysis plan. The adverse-event entries do not establish the timing or causal relationship of events, and their definitions cannot be assumed to match the primary endpoint. These limitations are specific to what the registry record reports and leave the clinical outcomes incompletely characterized.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: "A Pilot Study to Determine the Safety of Campath-1H (Anti-CD52) Therapy in Primary Renal Allograft Transplantation" — NCT00365846.
• Registry record last updated 2012-10-03; status last verified 2012-09.
• Results first posted 2012-07-30.
• 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.

19. Record Summary

The registry record describes NCT00365846, a completed Phase 2 pilot sponsored by University of Wisconsin, Madison. It enrolled 29 and is recorded as a single-group study with no masking and allocation listed as NA. The study dates are recorded as 2000-08 to primary completion in 2005-07.

The intervention is Campath-1H induction at day -1 and day 0 of kidney transplantation, followed by long-term CNI-free immunosuppression with sirolimus. The primary endpoint is incidence of allograft rejection, measured as participants over 3 years. The record lists secondary outcomes related to severe rejection, survival, infection, malignancies, and kidney allograft survival, but no analyses.

The primary endpoint result is not reported in the registry record. Safety entries list 19 affected among 28 at risk for serious adverse events and 28 affected among 28 at risk for other adverse events. These data describe the posted safety record but do not provide a controlled treatment comparison or the missing primary result.