Berinert (C1INH) vs Placebo for DGF/IRI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Berinert (C1INH) vs Placebo for DGF/IRI (NCT04696146), a randomized phase 1, phase 2 study. The primary outcome is Need for Dialysis in the First 30 Days Post-transplant.

2. Clinical Question

The primary endpoint concerns delayed graft function as represented by early post-transplant dialysis. The posted results show 10.0 of 20.0 participants in each arm with the endpoint. The estimated risk difference is 0.0, with a confidence interval from -0.310 to 0.310 and an unadjusted p-value of 1.0. These figures describe the observed trial data; they do not establish that the treatments are equivalent or that a difference is absent.

The study also posted outcomes for rejection episodes and donor specific antibodies at Month 6. Those outcomes provide additional descriptive information, but they do not replace the primary question. The registry record does not report a broader clinical outcome definition or a separate measure of graft function for the primary endpoint.

3. Trial Design

This was a Phase I/II randomized, placebo-controlled study with a parallel design. The registry identifies the allocation as randomized and records the masking as quadruple; the brief summary describes the study as double-blind. These registry descriptions are presented as recorded, and the record does not clarify the difference between them. The sponsor was Cedars-Sinai Medical Center.

The trial enrolled adults receiving a deceased-donor kidney transplant judged to be at high risk for delayed graft function, specified in the summary as KDPI >80. After eligible participants had consented and received an acceptable kidney offer, the Cedars-Sinai Research Pharmacy randomized them to study drug or placebo. The drug or placebo was prepared and conveyed to the operating room in a blinded manner, and the transplant surgeon administered it there. The summary describes Berinert at 500 units per kidney, delivered into the graft renal artery 1-2 hours before implantation. The placebo was normal saline in an identical volume.

The registry lists enrollment as 45. For the posted primary endpoint, each arm has 20.0 participants. The record does not explain the relationship between the overall enrollment figure and the endpoint arm counts, so no reason for that difference can be established.

The primary outcome was the need for dialysis in the first 30 days after transplant, expressed as participants who required at least one session. The two posted secondary outcomes were rejection episodes at Month 6 and development of donor specific antibodies at Month 6. The registry lists 6 outcome measures overall, while the posted results include the primary outcome and these 2 secondary outcomes.

The study is marked completed. The listed start date is 2021-03-03, and the primary completion date is 2022-07-31. The registry record does not report the detailed statistical analysis plan, eligibility criteria beyond the summary description, or the rationale for the enrollment target.

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 Need for Dialysis in the First 30 Days Post-transplant, measured over 30 days.

The primary endpoint was the need for dialysis in the first 30 days after transplant. It was defined as the number of participants requiring at least one dialysis session during that period. This is a binary, participant-level outcome: each person either met the endpoint or did not, according to the posted definition. The registry describes the endpoint as the percentage of patients enrolled who require dialysis, while the posted arm results are counts of participants.

Early dialysis is used as the trial’s measure of delayed graft function. It offers a clinically concrete event that can be counted, but it captures only the specific feature defined in the registry. The record does not report a broader definition of delayed graft function, such as an assessment that combines dialysis with other clinical or laboratory measures. Therefore, the posted endpoint should be read as dialysis during the stated period, not as a complete account of every aspect of graft function or ischemia/reperfusion injury.

In the posted results, 10.0 of 20.0 participants in the Berinert arm and 10.0 of 20.0 in the placebo arm met the endpoint. The reported risk difference is 0.0. That equality in observed counts is a description of this trial’s data; the confidence interval indicates that the estimate is not precise enough to rule out a range of differences. The endpoint does not by itself determine the mechanism behind an event, or establish the effects of treatment beyond the study population and outcome definition recorded.

7. Results Posted in the Registry

• Berinert: 50.0% (10/20) versus 50.0% (10/20) on control; risk difference 0.0 percentage points (95% CI -31.0 to 31.0), risk ratio 1.00 (0.54–1.86); unadjusted two-proportion z-test p = 1.000.

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.

Rejection Episodes at 6 Months

• 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:
  • Berinert: 15.0% (3/20) versus 0.0% (0/20) on control; risk difference 15.0 percentage points (95% CI -0.6 to 30.6); unadjusted two-proportion z-test p = 0.072.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Berinert and the control. The interval gives the range of effects that remain compatible with the data.

Development of Donor Specific Antibodies (DSA) at 6 Months

• 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:
  • Berinert: 5.0% (1/20) versus 5.0% (1/20) on control; risk difference 0.0 percentage points (95% CI -13.5 to 13.5), risk ratio 1.00 (0.07–14.90); 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 Berinert and the control. The interval gives the range of effects that remain compatible with the data.

The secondary endpoints add a limited view of outcomes at Month 6 beyond the primary 30-day dialysis measure. Together, they concern rejection episodes and donor specific antibodies, events that differ from the primary endpoint in both definition and timeframe. Their role is to broaden the descriptive picture, not to redefine the primary question or confirm its result.

Across the posted secondary comparisons, the pattern is not uniform: one outcome has a nonzero estimated risk difference, while the other has an estimate of 0.0. The intervals shown with those comparisons include zero. These observations should be considered in light of the small arm counts and the uncertainty reflected in the intervals. The posted data do not establish a clear, consistent pattern across the secondary outcomes.

These results relate to the primary result by offering additional endpoints from the same trial population, but they do not strengthen the precision of the primary dialysis estimate. Different endpoints can move in different directions without contradiction because they measure different events. The registry record does not report a prespecified hierarchy or explanation of how the secondary outcomes were intended to inform the primary question.

Unadjusted secondary results carry less weight when several outcomes are examined. In general, repeated testing can make apparently notable findings more likely by chance, and an adjustment or prespecified hierarchy may help guide interpretation. No such strategy is reported in the registry record. The secondary findings are best treated as descriptive and hypothesis-generating rather than as stand-alone confirmatory evidence.

The record lists 6 outcome measures, but the results include the primary endpoint and 2 posted secondary endpoints. The registry does not report the remaining outcome results in the registry record. That limits any attempt to describe the full outcome pattern, and it makes it especially important not to overstate what the posted secondary results imply.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Rejection Episodes at 6 Months
• Development of Donor Specific Antibodies (DSA) at 6 Months

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: participants are counted according to whether they required at least one dialysis session during the first 30 days after transplant. For this type of outcome, a basic arm summary consists of the event count and the number of participants contributing to that summary. The posted results give 10.0 events among 20.0 participants in each arm. The registry’s comparison is expressed as a risk difference, which describes the difference between the event proportions in the two arms. Here the reported estimate is 0.0.

What does a risk difference describe?

In general, a risk difference is an absolute comparison of outcome probabilities: it asks how far apart the two observed proportions are. It is distinct from a relative measure, which expresses one arm in relation to the other. An estimate of 0.0 means the observed proportions are equal in this comparison. It does not imply that every participant had the same outcome, and it does not by itself show that the underlying treatment effects are equal.

The confidence interval places uncertainty around the estimated risk difference. In general, a confidence interval is a range of values compatible with the data and the calculation method used, under the assumptions of that method. Here the reported interval is -0.310 to 0.310. Its inclusion of zero is consistent with the reported point estimate, but its width also shows that the data allow a range of possible differences. The registry record does not state the specific method used to calculate this interval, so it should not be attributed to a particular procedure.

How should the p-value be read?

The primary comparison reports an unadjusted p-value of 1.0. In general, a p-value summarizes how compatible the observed data are with a specified null hypothesis, given the statistical test and its assumptions. It is not the probability that the null hypothesis is true, and it does not measure the probability that a result will replicate. The registry record does not describe the test used for this primary comparison. The p-value should therefore be read as the posted unadjusted result, not as a complete account of the analysis method.

The trial’s randomized, parallel design assigns participants to Berinert or placebo. Random allocation is generally intended to reduce systematic differences between treatment groups, while masking is intended to limit effects of knowledge about allocation. The record lists randomized allocation and quadruple masking, while the study summary uses the term double-blind. It does not define who was included in the masking categories or explain the differing descriptions. Randomization and masking do not eliminate uncertainty from a small result set or address missing data and analysis choices on their own.

What can the secondary analyses add?

The registry posts counts and risk-difference comparisons for rejection episodes and donor specific antibodies at Month 6. These are binary outcomes like the primary endpoint, but they concern different events and a later timeframe. Their estimates should be considered separately rather than treated as interchangeable measures of the primary outcome. The registry record lists no reported analyses for either secondary outcome beyond the posted comparisons.

Multiple outcomes create a general interpretive concern: when many questions are examined, the chance of finding an apparently notable result can rise unless the analysis strategy accounts for that multiplicity. Whether an adjustment is needed, and what adjustment would be appropriate, depends on the prespecified aims and analysis plan. The registry record does not report a multiplicity procedure, a hierarchy among outcomes, or enough detail to determine which comparisons were prespecified.

There are also important reporting limits. The record does not report the primary statistical analysis plan, the test used for the primary p-value, the confidence-interval method, the analysis population, or the handling of missing outcomes. It does not report whether the primary analysis was intention-to-treat or based on another population definition. These omissions prevent a full assessment of whether the results follow a prespecified approach, how participants with unavailable data were handled, or whether any adjusted analyses were conducted.

The registry includes an enrollment figure of 45, while the posted primary endpoint results show 20.0 participants in each arm. The record does not explain this relationship. It is therefore not appropriate to infer why the endpoint counts differ from overall enrollment, or to assume that the endpoint results include every enrolled participant. The arm-specific counts shown with each outcome are the relevant denominators for interpreting that outcome.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.0, with a confidence interval from -0.310 to 0.310. The interval includes zero, which is consistent with no observed difference, but it also extends to values on both sides of zero. Thus, the data are compatible with a range of possible differences, not just the point estimate.

In general, a confidence interval conveys uncertainty around an estimate under the assumptions and method used to construct it. It is not a guarantee that the true value lies in the interval, nor does its inclusion of zero establish equivalence. To support an equivalence or non-inferiority conclusion, a study would ordinarily need a prespecified margin and an analysis designed for that question. Such a margin and analysis are not reported in the registry record.

The primary endpoint counts are 10.0 of 20.0 participants in each arm. With these posted arm counts, the point estimate is straightforward, but precision remains limited: the confidence interval is wide enough to include potentially meaningful differences in either direction. The record does not report the interval method, so interpretation should remain focused on the estimate and interval as posted rather than on an assumed calculation procedure.

The secondary outcome intervals also illustrate uncertainty, but they should be interpreted as exploratory context rather than as a replacement for the primary result. The registry does not report a multiplicity plan or a complete analysis plan for these outcomes. Across the posted results, the distinction between an observed estimate and its precision matters: a matching or small point estimate does not necessarily indicate a tightly determined effect.

12. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled. It does not state whether the primary outcome was the sole confirmatory endpoint, whether the secondary outcomes were prespecified as exploratory, whether a hierarchy was used, or whether p-values were adjusted for multiple comparisons. This missing information limits the strength of interpretation for secondary results, because examining several outcomes without an adjustment or stated hierarchy can make isolated findings less persuasive.

Missing-data handling is also not reported in the registry record. The posted arm counts for the primary outcome are 20.0 participants in each arm, while overall enrollment is listed as 45. The record does not explain whether every enrolled participant contributed to the primary endpoint, why the listed numbers differ, or how any participants without outcome data were treated. No assumptions about missing outcomes should be made from the posted counts alone.

The analysis population is not reported in the registry record. It does not state whether the results are based on all randomized participants, participants who received assigned treatment, or another defined group. Nor does it describe whether any participants were excluded after randomization. This prevents a full assessment of how the reported counts relate to the randomized trial population.

The registry record also does not report the detailed statistical analysis plan, including the specific test for the primary comparison, the method for constructing confidence intervals, or any covariate adjustment. It does not describe interim analyses or a sample-size justification. These details should not be inferred from the trial’s Phase I/II designation or from the posted result figures.

In general, a transparent analysis plan helps distinguish prespecified analyses from analyses selected after observing the data. Here, the posted primary estimate and secondary comparisons can be described, but the record does not provide enough methodological detail to evaluate all analytic decisions. This is a reporting limitation, not evidence that a particular method was or was not used.

13. Safety Results

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

Deaths

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: fever/sepsis (10.0%), acute kidney injury (10.0%), hyperkalemia (10.0%), pneumonia (5.0%), covid-19 (5.0%).

The registry posts serious adverse event figures for 20 participants at risk in each arm. Serious adverse events affected 6 participants in the Berinert arm and 4 in the placebo arm. Other adverse events affected 13 participants in the Berinert arm and 14 in the placebo arm. Deaths are recorded as 0 in both arms. These figures are counts of participants affected, not necessarily counts of every event experienced.

The listed serious adverse event terms include Fever/sepsis, Acute Kidney Injury, and Hyperkalemia at 10.0% each, as well as Pneumonia, COVID-19, and Urinary Tract Infection at 5.0% each. The record does not provide enough detail to determine the number of events for each person, whether terms overlap within participants, or how causality was assessed. The percentages should not be added together to estimate a total.

Safety counts are descriptive and should be read alongside the limited size of the posted groups and the absence of a detailed safety analysis plan in the registry record. They do not, on their own, establish whether an event was caused by study drug or whether the groups differ in safety.

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

The primary result shows equal observed counts for the dialysis endpoint: 10.0 of 20.0 participants in each arm required at least one dialysis session during the first 30 days after transplant. The reported risk difference is 0.0, with a confidence interval from -0.310 to 0.310. These are the central details for interpreting the primary comparison.

The result does not show that Berinert and placebo are equivalent. A point estimate of 0.0 is an estimate from the observed data, while the interval reflects uncertainty around that estimate. The interval includes values in both directions, so a range of possible differences remains compatible with the posted result. The registry record does not report an equivalence margin or a design intended to establish equivalence.

Nor does this result establish that Berinert has no effect, or that it improves or worsens outcomes. The unadjusted p-value of 1.0 is not a probability that the treatments are the same. It should be read with the point estimate, interval, endpoint definition, and limitations of the available analysis details.

The primary endpoint is specifically dialysis during the stated post-transplant period. It does not capture every aspect of delayed graft function, ischemia/reperfusion injury, graft performance, or longer-term health. The registry also posts two secondary outcomes at Month 6, but those outcomes are distinct from the primary endpoint and have their own uncertainty. No broad claim about clinical benefit or harm follows from the posted data alone.

The study was a Phase I/II trial described as assessing safety and limited efficacy, and the endpoint groups shown are small. The record does not report the full statistical plan, missing-data handling, analysis population, or a multiplicity strategy. Accordingly, the findings are best understood as a limited report of the observed trial outcomes, not as a definitive answer about treatment effects in all kidney transplant recipients or in populations beyond those described.

15. Why This Trial Matters Statistically

This trial is statistically informative because it puts a concrete estimate beside a result that might otherwise be summarized only as no difference observed. The primary arm counts match, and the estimated risk difference is 0.0. But the confidence interval from -0.310 to 0.310 shows why an estimate and its precision must be considered together. Equal observed proportions do not necessarily make the underlying effect precisely known.

The study also illustrates the importance of separating a primary endpoint from secondary outcomes. The primary question concerns dialysis in the first 30 days, while the posted secondary outcomes concern rejection episodes and donor specific antibodies at Month 6. Their results may add descriptive context, but they address different events, and unadjusted secondary comparisons deserve caution when the registry does not report a multiplicity plan.

Several design and reporting details matter for evaluating the evidence. The trial is randomized and placebo-controlled, but the record uses both double-blind and quadruple-masking descriptions without clarifying the distinction. Overall enrollment is listed as 45, while the primary outcome arm counts are 20.0 each; the registry does not explain the relationship. It also does not report the analysis population or missing-data methods.

These features make the study useful as an example of how to read a small clinical trial result: distinguish observed counts from treatment effects, read intervals rather than relying on a p-value alone, and avoid treating secondary findings as definitive without a stated plan. The record supports careful description, but its reporting limits constrain stronger statistical conclusions.

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.

The primary endpoint is narrowly defined as at least one dialysis session during the first 30 days after transplant. The registry record does not provide a wider composite or alternative definition of delayed graft function, so the result should not be generalized to every aspect of graft function or ischemia/reperfusion injury.

The posted primary result has 20.0 participants in each arm, whereas the registry lists enrollment as 45. The record does not explain the difference. It does not report whether all enrolled or randomized participants contributed data, whether any observations were missing, or how exclusions and missing outcomes were handled. This leaves uncertainty about the relationship between enrollment and the analyzed endpoint groups.

The record describes masking in two ways: its masking field says quadruple, while the brief summary calls the study double-blind. It does not explain the terms or identify who was masked. This is a reporting ambiguity rather than evidence that masking failed.

Further limitations are the absence of a reported statistical analysis plan, a stated analysis population, the primary test and interval method, a multiplicity strategy, and interim-analysis details. The registry also does not report a sample-size justification. Although a planning illustration is described in general terms, no sample-size result is available to assess, and such a planning calculation would not be observed power.

The registry lists 6 outcome measures, but only the primary result and 2 secondary results are represented in the registry entries for this page. The full outcome record therefore cannot be assessed from these results alone. The secondary comparisons are unadjusted, and their interpretation is constrained by multiplicity and uncertainty. Finally, the findings concern the specific population described in the record: adult recipients of high-risk deceased-donor kidney allografts.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Berinert (C1INH) vs Placebo for DGF/IRI — NCT04696146.
• Registry record last updated 2024-12-04; status last verified 2024-11.
• Results first posted 2023-09-29.
• 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.

20. Record Summary

NCT04696146 is a completed Phase I/II randomized, parallel, placebo-controlled study sponsored by Cedars-Sinai Medical Center. It assessed preoperative Berinert, described as C1 inhibitor at 500 units per kidney, compared with normal saline placebo in adults receiving deceased-donor kidney allografts considered at high risk for delayed graft function.

The primary outcome was need for at least one dialysis session in the first 30 days after transplant. The posted counts were 10.0 of 20.0 participants in each arm; the risk-difference estimate was 0.0, with a confidence interval from -0.310 to 0.310 and an unadjusted p-value of 1.0. The registry also posted results for rejection episodes and donor specific antibodies at Month 6.

The record does not report the detailed analysis plan, analysis population, missing-data approach, or multiplicity strategy. These limits, along with the uncertainty around the primary estimate, call for a descriptive rather than definitive reading of the posted results.