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 Safety & Tolerability of Berinert® (C1 Inhibitor) Therapy to Prevent Rejection (NCT01134510), a randomized phase 1, phase 2 study. The primary outcome is Post-transplant Biopsy to Identify Rejection Episodes.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01134510 |
| Phase | Phase 1, Phase 2 |
| Condition | Kidney Transplantation |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 20 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Stanley Jordan, MD |
| Results posted | Yes |
2. Clinical Question
Population
Highly HLA-sensitized patients who had received desensitization treatment and were awaiting kidney transplantation. The registry describes patients with antibodies to human leukocyte antigens as the group of interest. Its enrollment was 20.
Intervention
C1 esterase inhibitor, also identified as Berinert, in addition to standard-of-care post-transplant immunosuppressive therapy. The brief summary describes dosing as 20 units/kg daily x 3 days, then twice weekly x 3 weeks.
Comparator
Normal saline placebo in addition to standard-of-care post-transplant immunosuppressive therapy.
Primary question
At the 6-month protocol biopsy, how many rejection episodes were identified in each randomized group? The posted counts were 2 with C1 esterase inhibitor and 3 with normal saline, among 9 patients in each arm who completed the biopsy.
3. Trial Design
This was a randomized, triple-masked, parallel-group Phase I/II trial in kidney transplantation. The registry lists an enrollment of 20. The planned groups were C1 esterase inhibitor plus standard-of-care immunosuppressive therapy and normal saline placebo plus standard-of-care therapy. The registry identifies Stanley Jordan, MD, as the sponsor. The study is marked completed; its recorded start was 2011-08 and its primary completion was 2013-11.
The intended population was highly HLA-sensitized patients who had undergone desensitization treatment and were awaiting kidney transplant. The brief summary describes the clinical concern as antibody-mediated rejection after transplantation, including in patients with donor-specific antibodies. Once transplanted, participants were to receive the standard post-transplant immunosuppressive protocol, with the intervention group also receiving Berinert. The regimen described in the summary was 20 units/kg daily x 3 days, followed by twice weekly x 3 weeks.
The primary outcome was a count of rejection episodes identified through a routine kidney biopsy at 6 months. The registry reports that 9 patients in each arm completed that protocol biopsy. One patient in the placebo arm was withdrawn before the biopsy, and one patient in the treatment arm refused it. Those accounting details matter because the primary outcome counts are posted for the biopsy completers, not for every enrolled participant.
Serum creatinine and donor-specific antibody measures for Class I and Class II were also posted as secondary outcomes at 6 months. The registry does not report which individuals were masked or give further detail about allocation procedures, follow-up beyond the listed outcome timeframes, or the statistical analysis 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
| Stage | C1 Esterase Inhibitor | Placebo |
|---|---|---|
| STARTED | 10 | 10 |
| Day 2 | 10 | 10 |
| Week 2 | 10 | 10 |
| Week 2 | 10 | 10 |
| Week 3 | 10 | 10 |
| Week 3 | 10 | 10 |
| Week 4 | 10 | 10 |
| Week 4 | 10 | 10 |
| Month 1 | 10 | 10 |
| Month 3 | 10 | 9 |
| COMPLETED | 10 | 9 |
| NOT COMPLETED | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: 9 patients in each arm completed 6 month protocol biopsy. 1 patient in the placebo arm was withdrawn before 6M biopsy. 1 patient in treatment arm refused protocol biopsy.
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 | C1 Esterase Inhibitor | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 10 | 20 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 10 | 10 | 20 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 46 (SD 14) | 47 (SD 16) | 47 (SD 15.5) |
| Sex: Female, Male: Female | Participants | 8 | 3 | 11 |
| Sex: Female, Male: Male | Participants | 2 | 7 | 9 |
| Region of Enrollment: United States | participants | 10 | 10 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Post-transplant Biopsy to Identify Rejection Episodes, measured over 6 month.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Episode of rejection |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the number of rejection episodes identified at a routine kidney biopsy 6 months after transplant. It is a count outcome: the posted values are episode counts, rather than a mean measurement or a rate over person-time. The registry says the biopsy was intended to screen for episodes of acute rejection.
The registry’s definition of antibody-mediated rejection combines clinical, laboratory, and tissue information. It refers to deterioration in allograft function, measured using serum creatinine and estimated Glomerular Filtration Rate, in a high-risk recipient with a history of donor-specific antibodies. It also requires an association with donor-specific antibody, usually increasing in strength, measured by luminex techniques, and biopsy evidence of capillaritis, inflammation, and C4d deposition. This makes the endpoint more than a laboratory marker alone: it relies on biopsy findings alongside other evidence.
A biopsy-based endpoint is used to identify rejection episodes in the transplanted kidney, including episodes that may be detected through tissue findings. The posted primary counts were 2 in the C1 esterase inhibitor arm and 3 in the normal saline arm, with 9 patients in each arm completing the protocol biopsy. The registry does not report a formal comparative analysis for these counts, so the values should be read descriptively rather than as an estimated treatment effect with quantified uncertainty.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary results are descriptive counts from the 6-month protocol biopsy: 2 rejection episodes were posted for C1 esterase inhibitor and 3 for normal saline. The registry reports 9 biopsy completers in each arm. These counts alone do not establish whether the groups differ beyond what could occur through chance variation. The registry record does not report a formal statistical comparison, an interval estimate, or a model for the primary count outcome.
There are also reasons not to treat the biopsy counts as complete outcome information for everyone enrolled. One placebo-arm patient was withdrawn before the 6-month biopsy, and one treatment-arm patient refused the protocol biopsy. The record does not explain whether additional rejection information was collected for these patients or how their outcomes were handled in an analysis. Thus, the primary result is specifically grounded in the reported biopsy-completer counts; it should not be generalized to a full-population estimate without information on missing outcomes and the analysis population.
The secondary outcomes describe serum creatinine and donor-specific antibody measurements at 6 months. Recalculated, unadjusted mean-difference intervals for all three secondary comparisons include zero. Their unadjusted p-values are also posted, but the registry lists no reported analyses. These calculations are not a sponsor-reported analysis and should not be treated as prespecified confirmatory results. The intervals indicate substantial uncertainty about the direction and size of the group differences; they do not establish equivalence or show that a difference is absent.
The secondary measures address different aspects of post-transplant status from the biopsy-defined primary endpoint. A laboratory measurement or antibody intensity score is not interchangeable with a count of biopsy-identified rejection episodes. The data therefore do not support replacing the primary endpoint with a favorable-looking secondary pattern, nor do the secondary results resolve the uncertainty around the primary counts.
Overall, the record documents a randomized comparison and posts primary counts alongside secondary descriptive measurements. It does not provide a reported inferential analysis of the primary endpoint, an analysis plan, or a stated multiplicity approach for the secondary outcomes. The appropriate reading is limited: these results describe what was recorded in this small trial, while the precision and robustness of comparative conclusions remain uncertain.
9. Statistical Methods Explained
The primary outcome is a count of rejection episodes, while the secondary outcomes are continuous measurements reported as means with standard deviations. These outcome types call for different statistical summaries. A mean difference is natural for comparing continuous outcomes, but a count outcome may need a count-based comparison whose assumptions depend on how counts are distributed and how they were collected. The registry record does not report a model or a formal comparison for the primary count outcome. It states that values were missing or not estimable for a two-arm comparison, so no recalculated primary comparison is presented.
What does a count outcome represent?
A count records how many events occurred in the defined observation period. The primary result is the number of episodes identified at the protocol biopsy, not a percentage or a rate. Rates usually require person-time or another exposure denominator, and no such rate analysis is reported. The posted count also does not by itself describe how many patients experienced one or more episodes, because the record does not provide that patient-level distribution. Counts may vary more than a simple model expects when observations are heterogeneous or events cluster; this is the general issue of over-dispersion. Whether over-dispersion applied here, and whether it was assessed, are not reported in the registry record.
There are only posted arm-level counts for the primary endpoint. Without a reported inferential method and its assumptions, it is not appropriate to infer a p-value or interval from those counts. The primary result should therefore be read as a descriptive comparison. The registry’s note that a two-arm comparison was not estimable is not evidence that the groups are equal; it means a comparative estimate is not available in the posted results.
How should the secondary mean differences be read?
For each continuous secondary outcome, the recalculated mean difference is oriented as C1 esterase inhibitor minus placebo. A value below zero indicates a lower observed mean in the intervention group, while a value above zero indicates a higher observed mean. The estimates use the posted group means and standard deviations and are unadjusted recalculations, not analyses reported by the sponsor. The registry lists no reported analyses for these outcomes.
An interval around a mean difference describes a range of values compatible with the data under the calculation’s assumptions. A narrow interval indicates greater precision than a wide interval. When an interval includes zero, the data do not clearly distinguish a difference in one direction from no mean difference under that unadjusted calculation. This does not prove equality, and the interval’s exact confidence level is not reported in the registry record. The recalculated intervals for the secondary comparisons include zero, and the posted unadjusted p-values do not substitute for a prospectively specified analysis plan.
The p-values are unadjusted. They do not account for testing multiple outcomes, and the registry does not state whether any multiplicity adjustment was planned. They should therefore be interpreted cautiously, especially because the outcomes are secondary and no sponsor-reported analysis is listed. No claim about a prespecified threshold for interpreting these p-values can be made from the record.
What do the planning illustrations mean?
The sample-size illustrations are planning calculations based on the observed effects, rather than a record of the trial’s design justification or observed power. They assume a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is set to a stated fraction of the observed effect. The illustrations ask how many participants per arm would be needed under those assumptions for the specified power targets. They are sensitive to the observed effect, which can be unstable in a small trial, and they are not evidence that the current trial had a particular probability of detecting an effect.
The registry does not report the assumptions used to plan the original enrollment, a sample-size justification, or whether interim analyses were performed. The posted planning illustrations cannot fill those gaps. They should be treated as hypothetical planning aids, not as evidence of adequate or inadequate power for the primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three secondary outcomes in addition to the primary biopsy count. It does not report whether the study prespecified a testing hierarchy, adjusted for multiple comparisons, or treated the secondary measures as exploratory. The recalculated secondary p-values are unadjusted. When several outcomes are examined, unadjusted tests do not account for the chance of obtaining an apparently notable result across the set. No multiplicity-adjusted result is reported, so the secondary comparisons should not be interpreted as confirmatory evidence.
For the primary biopsy outcome, the registry states that 9 patients in each arm completed the 6-month protocol biopsy. It also reports that one placebo-arm patient was withdrawn before the biopsy and one treatment-arm patient refused it. The record does not report the outcomes for these patients at that timepoint, whether any alternative outcome ascertainment was available, or how missing primary outcome data were handled. Nor does it state an analysis population such as intention-to-treat or per-protocol.
The secondary outcomes are posted with 10 participants per arm, but the registry does not explain the relationship between these denominators and completion of the protocol biopsy, or describe missing-data handling for the secondary measures. The difference in reported denominators across outcomes should not be silently reconciled by assumption. The record also does not report whether missingness was considered related to clinical status or treatment assignment.
No interim analyses, stopping rules, or detailed statistical analysis plan are reported in the registry record. Those omissions limit assessment of how outcomes and analyses were selected and how incomplete data may have affected the results. They do not establish that such procedures were absent; they mean that the registry record does not report them.
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 |
|---|---|---|---|
| Placebo | 2 | 10 | 20.0% |
| C1 Esterase Inhibitor | 1 | 10 | 10.0% |
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 |
|---|---|
| Placebo | 0 of 10 |
| C1 Esterase Inhibitor | 0 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | C1 Esterase Inhibitor |
|---|---|---|---|
| Post op Vascularization | Surgical and medical procedures | 1 of 2 | 0 of 10 |
| Hyperkalemia | Renal and urinary disorders | 1 of 10 | 0 of 10 |
| Perinephric Hematoma | Surgical and medical procedures | 0 of 10 | 1 of 10 |
Serious events with the highest arm-level rate: post op vascularization (50.0%), hyperkalemia (10.0%), perinephric hematoma (10.0%).
The registry reports serious adverse events affecting 2 of 10 participants at risk in the placebo group and 1 of 10 participants at risk in the C1 esterase inhibitor group. It reports 0 other adverse events affecting participants at risk in each group. These are descriptive safety figures; they do not establish that the intervention caused or prevented an event, and the record does not provide a comparative statistical analysis of these counts.
The listed serious-event terms include Post op Vascularization at 50.0%, Hyperkalemia at 10.0%, and Perinephric Hematoma at 10.0%. The registry record does not explain the denominator or calculation underlying those term percentages, so they should not be treated as incidence estimates without that context. The listed terms also do not, by themselves, indicate whether events were judged related to treatment.
Deaths are not reported in the posted adverse-event data. The event figures should be read alongside the trial’s limited size and the registry’s lack of a reported safety comparison. They describe events recorded in the trial, not a definitive estimate of comparative safety.
12. What the Result Does, and Does Not, Mean
The posted results describe a randomized comparison of C1 esterase inhibitor and normal saline in highly HLA-sensitized kidney-transplant patients. For the primary biopsy outcome, the registry records 2 rejection episodes in the intervention arm and 3 in the placebo arm among 9 patients per arm who completed the protocol biopsy. This is a small descriptive difference in counts, but the registry does not provide a formal comparative estimate or quantify uncertainty for that endpoint.
The primary result does not establish that the intervention reduces rejection, nor does it show that the groups are equivalent. The available count comparison is not accompanied by an analysis that accounts for uncertainty, and two patients did not complete the reported biopsy procedure for different stated reasons. The registry does not say how their outcomes were handled. These limitations constrain what can be concluded from the counts.
The secondary laboratory and antibody measures offer additional descriptions of the groups, but their unadjusted recalculated intervals include zero and the record lists no sponsor-reported analyses. They do not provide a basis for overriding or confirming the primary result. Nor should a failure to obtain a clearly separated estimate be described as proof that there is no effect: imprecise data can be compatible with a range of possible differences.
The trial therefore contributes a record of outcomes and adverse events from a randomized Phase I/II study, but the posted information is not sufficient for a definitive comparative conclusion. The registry does not report a detailed statistical plan, multiplicity approach, primary endpoint analysis, or handling of missing outcomes. Those gaps affect interpretation of both the apparent direction of the results and their precision. The results should be understood as limited evidence from this trial, rather than a complete answer about treatment effect.
13. Why This Trial Matters Statistically
This trial illustrates why the endpoint type and the level of analysis matter. Its primary outcome is a count of biopsy-identified rejection episodes, whereas the secondary outcomes are continuous laboratory and antibody measurements. These summaries cannot be treated as interchangeable, and the methods used to estimate uncertainty for a continuous mean difference do not automatically provide an appropriate analysis for a count outcome.
It also shows why enrollment and outcome denominators should be distinguished. The registry lists enrollment of 20, while the primary biopsy counts are reported among 9 completers in each arm. The record gives specific reasons for the two incomplete biopsies, but does not report how those missing outcomes were addressed analytically. That makes the outcome population central to understanding what the primary numbers represent.
Finally, randomized allocation does not eliminate the need for transparent analysis and reporting. The record does not provide a formal comparison for the primary count outcome, a stated multiplicity plan for secondary measures, or an analysis population. Recalculated secondary comparisons can help describe the posted summary statistics, but they do not replace the sponsor’s analysis or an analysis plan. The trial is statistically instructive because it highlights how uncertainty, incomplete outcomes, multiple measures, and endpoint-specific methods shape the strength of conclusions that registry results can support.
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 primary endpoint is posted as episode counts, with no formal two-arm analysis or uncertainty interval reported. The registry states that values were missing or not estimable for a two-arm comparison. As a result, the central outcome is available descriptively but not as a quantified comparative effect. The record also does not provide patient-level counts, so it is unclear from the posted summary how episodes were distributed across participants.
Biopsy completion was incomplete in both groups for different stated reasons: one placebo-arm patient was withdrawn before the biopsy and one treatment-arm patient refused the protocol biopsy. The registry does not report whether missing outcomes were otherwise ascertained or how these cases were handled. The secondary outcomes have different posted group sizes, and the record does not explain missing-data procedures or the relationship between those outcome populations and the biopsy population.
The secondary estimates are recalculated from summary statistics and are unadjusted. They cannot account for individual-level features or replace a sponsor-reported analysis; none is listed. The registry also does not report a multiplicity approach, detailed statistical analysis plan, sample-size justification, interim-analysis procedures, or the original rationale for enrollment. The planning illustrations based on observed effects do not address those omissions.
Finally, the adverse-event summary is descriptive. The denominator behind the listed serious-event term percentages is not reported, and the record does not give a comparative safety analysis or report deaths. These limitations do not imply that unreported procedures or information did not exist, but they restrict what can be assessed from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety & Tolerability of Berinert® (C1 Inhibitor) Therapy to Prevent Rejection — NCT01134510.
- Registry record last updated 2017-03-21; status last verified 2017-02.
- Results first posted 2015-08-03.
- 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 record describes a completed randomized, triple-masked, parallel-group Phase I/II trial of C1 esterase inhibitor versus normal saline in highly HLA-sensitized kidney-transplant patients. Enrollment was 20, and both groups received standard-of-care post-transplant immunosuppressive therapy.
The primary endpoint was the number of rejection episodes identified at a 6-month protocol biopsy. Counts were 2 for C1 esterase inhibitor and 3 for normal saline among 9 biopsy completers in each arm. One patient in each arm did not complete the protocol biopsy, for the reasons stated in the record. Three secondary outcomes were posted: serum creatinine and donor-specific antibodies Class I and Class II.
The registry does not report a formal primary comparison, sponsor-reported analyses, a detailed statistical plan, or procedures for handling missing outcomes and multiplicity. Secondary mean-difference calculations are unadjusted recalculations. Safety figures are descriptive, and the denominator for the listed serious-event term percentages is not reported.