Steroid Withdrawal and Donor-specific Anti-HLA Antibodies in Renal Transplant Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Steroid Withdrawal and Donor-specific Anti-HLA Antibodies in Renal Transplant Patients (NCT02284464), a randomized phase 4 study. The primary outcome is Cases of Kidney Transplant Patients With DSA.

2. Clinical Question

The study rationale describes a trade-off of interest: steroid use is associated with complications, while withdrawal may affect acute rejection risk. It also identifies uncertainty about whether withdrawal is associated with newly detected donor-specific antibodies and how those antibodies relate to clinical and histological findings. Those statements explain the study question; they are not results from the comparison.

3. Trial Design

NCT02284464 is a completed phase 4, randomized, controlled study with parallel groups and no masking. Its official title describes a prospective study of steroid withdrawal and new donor-specific anti-HLA antibodies in renal transplant patients. The registry record lists enrollment of 230 participants, with a start date of 2015-02 and primary completion in 2019-07.

The two treatment strategies were prednisone continuation with tacrolimus and mycophenolate, and prednisone withdrawal with tacrolimus and mycophenolate. For the withdrawal group, the arm description specifies normal treatment for the first 90 days followed by steroid withdrawal while continuing the other drugs. The comparator arm is described as the normal treatment arm. The record does not report masking, which is consistent with its explicit classification as having none.

The primary outcome was the number of participants with kidney transplant DSA over 24 months. The outcome description specifies measurements at baseline and at 3, 6, 12, 18 and 24 months. The primary result lists 39 participants in the steroids, tacrolimus and mycophenolate arm and 36 in the tacrolimus and mycophenolate arm. These outcome denominators are not the same as the registry enrollment figure; the record does not report why they differ or how the primary outcome population was selected.

The listed secondary domains include biopsy findings, acute rejection lesions, diabetes mellitus, lipid profile, blood pressure, renal function, adherence, and patient survival. The registry record does not report a detailed statistical analysis plan or the allocation procedure beyond identifying the study as randomized.

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.

Before assignment: Of the 230 patients, 125 were not randomized because of: screening failure 74; patient wishes 16; acute rejection 9; graft loss 9; died 3; lost to follow-up 1 and other causes 13. The main causes of screening failure were: creatinine \>2 mg/dl and subclinical rejection in the protocol biopsy at the third month. 105 patients were finally included

Overall Study

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 Cases of Kidney Transplant Patients With DSA, measured over 24 months.

The primary endpoint counts participants with donor-specific anti-HLA antibodies, or DSA, during a 24-month timeframe. DSA are antibodies directed against donor human leukocyte antigens. The study description focuses on de novo DSA, meaning antibodies newly detected after transplantation, and identifies this outcome as the main way to compare the steroid strategies.

The record states that DSA measurements were taken at baseline and at 3, 6, 12, 18 and 24 months. Baseline measurement can help distinguish antibodies already present from those detected later, while measurements during follow-up can capture when an antibody is observed. However, the registry record does not explain how measurements across visits were combined into the posted count, how a new case was defined, or how missing measurements were handled. The listed endpoint is a participant count, not a measure of antibody concentration or duration.

Counting participants with the event gives a direct comparison of how many people in each group met the outcome definition. It is useful when the research question concerns whether the event occurred, but the count alone does not describe the timing, persistence, or clinical consequences of DSA. The record lists related clinical and biopsy outcomes separately; it does not report a combined endpoint linking DSA with those outcomes.

7. Results Posted in the Registry

• Tacrolimus and Mycophenolate: 0.0% (0/36) versus 0.0% (0/39) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

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.

Number of Participants With Acute Rejection Lesions

• 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:
  • Tacrolimus and Mycophenolate: 11.5% (3/26) versus 7.1% (2/28) on control; risk difference 4.4 percentage points (95% CI -11.2 to 19.9), risk ratio 1.62 (0.29–8.91); unadjusted two-proportion z-test p = 0.578.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tacrolimus and Mycophenolate and the control. The interval gives the range of effects that remain compatible with the data.

Incidence of Diabetes Mellitus

• 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:
  • Tacrolimus and Mycophenolate: 16.7% (6/36) versus 25.6% (10/39) on control; risk difference -9.0 percentage points (95% CI -27.3 to 9.4), risk ratio 0.65 (0.26–1.61); unadjusted two-proportion z-test p = 0.343.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tacrolimus and Mycophenolate and the control. The interval gives the range of effects that remain compatible with the data.

Renal Function

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Tacrolimus and Mycophenolate: mean 1.40 versus 1.34 on control; difference 0.06 (95% CI -0.12 to 0.24), standardized effect d = 0.15; z-test p = 0.516.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tacrolimus and Mycophenolate and the control. The interval gives the range of effects that remain compatible with the data.

The registry record lists a range of secondary clinical and laboratory outcomes, including biopsy findings, acute rejection lesions, metabolic measures, renal function, adherence and survival. The posted numerical comparisons cover acute rejection lesions, diabetes mellitus and renal function. These outcomes address related but distinct questions: they do not measure the primary antibody endpoint, and they cannot substitute for it.

Across the posted comparisons, the estimates are uncertain and their confidence intervals include the relevant no-difference value. The unadjusted p-values also do not provide clear evidence of group differences. This pattern should be read as inconclusive rather than as proof that the treatment strategies are identical. The outcome counts and denominators are limited, and the record does not report an analysis plan that would establish which secondary outcomes were intended as confirmatory.

Secondary outcomes can add context to the primary result by showing whether other measured domains move in a consistent or contrasting direction. Here, the record does not provide enough detail to establish a common pattern across all the named secondary outcomes. It also does not report whether the secondary comparisons were adjusted for baseline values or other covariates. Different endpoint types have different scales and interpretations, so a difference in direction across outcomes would not, by itself, imply inconsistency.

Multiple unadjusted comparisons increase the chance that an apparently notable result could arise by chance when no true effect is present. Conversely, an unadjusted result that is not statistically distinguishable from no difference does not establish the absence of an effect. Because multiplicity handling and a hierarchy of outcomes are not reported, the secondary findings should be treated as supportive or exploratory context rather than as independent confirmation of the primary conclusion.

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

• Mean Score on the Protocol Biopsies in the Two Treatment Groups
• Number of Participants With Acute Rejection Lesions
• Incidence of Diabetes Mellitus
• Lipid Profile
• Blood Pressure
• Renal Function
• Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups
• Patient Survival

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a binary participant-level measure: each person is counted as having or not having the event according to the outcome definition. For this kind of endpoint, a risk is the proportion of participants with the event in a group. A risk difference expresses the difference between the groups’ observed risks. A value of zero means the observed risks are equal; a positive or negative value indicates which group has the higher observed risk, depending on the order used for the comparison. The primary comparison reports a risk difference of 0.0.

What does a confidence interval convey?

In general, a confidence interval describes the range of values compatible with the observed data under a specified statistical method. It conveys uncertainty about an estimated effect, rather than the range of individual participant outcomes. For a risk difference, zero is the value representing no observed difference. If an interval includes zero, the data do not distinguish the estimate from no difference at the interval’s stated level. The registry record does not report the confidence level or calculation method for the primary interval, so those details cannot be assessed from the posted record.

Why are zero events a special case?

When there are no events in either group, the observed risk difference is necessarily zero. General statistical methods do not all handle this situation in the same way. Some approaches can produce an interval that reflects uncertainty despite observing no events; other calculations may return a zero-width interval. The primary result lists an interval from 0.0 to 0.0, but the registry record does not identify the method behind it. That reported interval should therefore be read cautiously and not treated as proof that the underlying risk difference must be zero.

How should unadjusted comparisons be read?

The secondary outcome comparisons include risk differences for participant-count outcomes and a mean difference for renal function. A mean difference compares group averages; a positive estimate means the average in the second named arm is higher under the comparison’s stated ordering. The posted renal function result is expressed in mg/dl, with standard deviations reported for each group. Standard deviation describes variation among participant measurements, while a standard error describes uncertainty in an estimated group mean. The registry record lists standard errors for the renal function group means.

The secondary p-values are unadjusted. A p-value measures how unusual data at least as discrepant as those observed would be under a specified null model; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. Because multiple outcomes are listed, unadjusted values do not account for the possibility of chance findings across repeated comparisons. The registry record does not report a multiplicity strategy or a full set of prespecified hypotheses, which limits interpretation of these results as confirmatory evidence.

What are the planning illustrations?

The posted planning illustrations estimate participants per arm for 80% power and participants per arm for 90% power under stated assumptions: a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect set to a stated fraction of the observed effect. For acute rejection lesions, the illustration gives 687 participants per arm for 80% power when planning for 100% of the observed effect, 1,157 when planning for 75%, and 2,457 when planning for 50%. For diabetes mellitus, the corresponding figures are 324, 599 and 1,397. For renal function, they are 698, 1,241 and 2,791. These figures are planning illustrations derived from the observed effects, not the trial’s original design justification and not observed power. The registry record does not report the trial’s own sample-size justification.

These methods explain the types of estimates in the registry record, but do not establish which tests or models the investigators used for the posted results. The record does not report a detailed statistical plan, adjustment variables, analysis populations, or handling of repeated measurements. Those omissions matter because different valid methods can yield different uncertainty estimates, especially with small outcome denominators or no observed events.

11. Confidence Intervals and Precision

The primary outcome lists 0 events among 39 participants in the steroid-continuation arm and 0 among 36 in the withdrawal arm. Its risk-difference interval is reported as 0.0 to 0.0. Although that interval has no displayed width, the record does not report how it was calculated. With no observed events, a point estimate of zero reflects the observed counts, but the sample does not establish that the population difference is exactly zero. The displayed interval should not be interpreted as complete certainty.

The secondary comparisons provide a further view of precision. Their confidence intervals span both the no-difference value and values in either direction. This means the posted estimates are compatible with more than one interpretation, including no clear difference. The width of an interval is informative about precision: wider intervals indicate less precise estimation under the method used. The registry record does not identify the confidence level or calculation methods for these comparisons.

Outcome denominators are limited relative to the enrollment figure, and the record does not explain the difference. It also does not report a missing-data analysis or the number of participants with measurements at each visit. These gaps make it difficult to judge whether the posted precision reflects all randomized participants or only a subset with available outcomes. A nonsignificant unadjusted p-value, where reported for secondary outcomes, does not by itself demonstrate equivalence or exclude effects that the data estimate imprecisely.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and multiple secondary outcomes, but it does not report how the investigators handled multiplicity. Multiplicity arises when several outcomes, time points, or comparisons are tested. Even if each test is interpreted on its own, examining many results can increase the chance of at least one apparently unusual finding. Common approaches include prespecifying a hierarchy, adjusting significance thresholds, or identifying secondary analyses as exploratory. The record does not say whether any of these approaches were used.

The primary outcome description includes DSA measurements at baseline and at 3, 6, 12, 18 and 24 months, while the outcome timeframe is 24 months. The record does not explain whether the endpoint counts participants with DSA at the final visit, at any post-baseline visit, or under another rule. It also does not report a method for handling missing measurements, participants who discontinue, or outcomes that could not be assessed. Therefore, the effect of missing data on the posted counts cannot be evaluated.

The registry reports enrollment of 230 and primary outcome denominators of 39 and 36. It does not report participant flow or explain how the outcome denominators relate to the enrolled population. Nor does it identify whether the primary analysis followed intention-to-treat, per-protocol, or another analysis population. These are important distinctions in a randomized study because excluding participants after randomization can affect how well a comparison preserves the randomized groups.

Reported analyses are not listed in the registry record. The record also does not report a statistical analysis plan, an interim analysis plan, covariate adjustment, or the approach used for repeated measurements. These details should not be inferred from the design description or from the posted outcome values. Their absence limits assessment of prespecification, risk of selective reporting and robustness of the analyses.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: infection (22.6%), cardiovascular disease (5.8%), neoplasm (3.8%).

The serious adverse event summary lists 10 affected participants among 52 at risk in the steroids, tacrolimus and mycophenolate group, and 15 among 53 at risk in the tacrolimus and mycophenolate group. Other adverse events are listed as 0 in each group, and deaths are listed as 0 in each group. These are descriptive registry counts; they do not establish that an event was caused by a treatment.

The registry record lists infection, cardiovascular disease and neoplasm among the top serious adverse event terms, with values of 22.6%, 5.8% and 3.8%, respectively. It does not clarify the denominator or counting rule behind these term percentages in the available record. They should not be interpreted as participant-level risks without that information.

The groups at risk for safety outcomes differ from the primary outcome denominators. The record does not explain the difference, give event timing, or report an adjusted comparison of safety outcomes. These summaries can describe what was recorded, but they do not alone establish comparative safety or causation.

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

The primary posted result is a simple observation: no DSA cases were recorded in either reported group over the stated 24-month timeframe. The risk difference is reported as 0.0. That equality applies to the observed outcome counts and does not establish that steroid withdrawal and continuation have equal effects in the population of interest.

A zero-event result is compatible with uncertainty about how often an event might occur beyond the participants represented in the result. The primary interval is reported as 0.0 to 0.0, but the method behind it is not reported. Its appearance should not be taken to mean that all plausible population differences have been ruled out. The record’s outcome denominators and the unexplained gap between those denominators and enrollment further limit what can be concluded.

The secondary results offer additional descriptive information but do not resolve the primary uncertainty. Their estimates are imprecise, and the comparisons are unadjusted. The record does not describe a multiplicity approach or the prespecified role of each secondary outcome, so those results should not be treated as definitive evidence for or against a treatment effect.

The findings do not establish a treatment recommendation. They describe the outcomes posted in the registry and the limits of the available statistical detail. A more complete interpretation would require the outcome definitions, analysis populations, missing-data information and methods used to calculate the estimates and intervals.

15. Why This Trial Matters Statistically

This trial raises a statistically important question about how to interpret an endpoint with no observed events in either randomized group. Equal counts can produce an observed difference of zero, but a point estimate and an uncertainty interval are separate pieces of information. When the interval is reported as 0.0 to 0.0, knowing the calculation method is essential before treating that display as informative about population-level precision.

The record also illustrates why enrollment and outcome denominators need to be distinguished. Enrollment is reported as 230, while the primary outcome is reported with 39 and 36 participants in the two arms. Those figures answer different descriptive questions. Without participant flow or an account of the analysis population, readers cannot determine how the primary result relates to the full randomized population.

Finally, the study includes several secondary outcomes, with unadjusted comparisons and planning illustrations based on observed effects. The illustrations show how assumed target effects influence hypothetical sample-size requirements, but they do not describe the trial’s original planning or its achieved power. Separating descriptive findings, inferential uncertainty and planning assumptions is central to reading these results accurately.

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 trial-specific limitations of interpretation follow from the registry record. The primary outcome denominators are substantially different from the enrollment figure, and the record does not explain this difference. Participant flow, allocation details, reasons for exclusion, and the analysis population are not reported. Consequently, the relation between the randomized cohort and the posted outcome population is unclear.

The endpoint description gives several DSA measurement visits but does not define the rule used to classify a participant as having a new case. It does not say whether the count reflects an event at any post-baseline visit, the final visit, or a different summary. Missing measurements and withdrawal from follow-up are not addressed. These omissions constrain interpretation of the reported zero counts.

The primary interval is displayed as 0.0 to 0.0, while the record does not report the calculation method or confidence level. The record also contains no reported primary analysis, detailed statistical plan, or multiplicity approach. Secondary comparisons are unadjusted, and the registry does not state whether covariates or repeated measurements were incorporated.

Safety summaries use denominators that differ from the primary outcome denominators, with no explanation of the analysis populations or event attribution. The serious adverse event term percentages also lack a reported denominator in the available record. These limitations do not change the recorded counts, but they make broader comparisons and causal interpretation difficult.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Steroid Withdrawal and Donor-specific Anti-HLA Antibodies in Renal Transplant Patients — NCT02284464.
• Registry record last updated 2020-04-14; status last verified 2019-12.
• Results first posted 2020-04-14.
• 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

NCT02284464 is a completed, randomized, unmasked, parallel-group phase 4 study of prednisone withdrawal versus continuation in kidney transplant patients. The registry reports enrollment of 230 and a primary outcome timeframe of 24 months. The posted primary counts show 0 of 39 participants with DSA in the continuation group and 0 of 36 in the withdrawal group; the reported risk difference is 0.0, with an interval from 0.0 to 0.0.

The record also lists secondary outcomes and serious adverse event summaries. It does not report the primary analysis method, analysis population, missing-data handling, participant flow, or multiplicity approach. Those missing details limit how far the posted estimates can be generalized or interpreted.