Supplementation With Cholecalciferol in Dialysis Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Supplementation With Cholecalciferol in Dialysis Patients (NCT01974245), a randomized phase 2 study. The primary outcome is Change From Baseline in Interleukin-6 at 12 Weeks..

2. Clinical Question

The rationale described in the registry is that vitamin D may influence immune markers. It specifically discusses cathelicidin, an antimicrobial peptide, and proinflammatory cytokines. The listed measurements also include C-reactive protein, tumor necrosis factor-α, serum 25(OH)D, and markers assessed in monocytes. These details describe the study’s biological focus; they do not establish what the trial found.

The question is therefore about a comparative change in a laboratory marker over the stated treatment period, rather than a reported clinical infection outcome. The registry lists chronic kidney disease as the condition and identifies both hemodialysis and peritoneal dialysis in the study description. It does not report separate primary-outcome results by dialysis type or give a subgroup analysis. Nor does it report the primary endpoint values needed to assess the direction, size, or precision of any between-group difference.

3. Trial Design

The registry identifies NCT01974245 as a completed, randomized, phase 2, parallel-group trial sponsored by Federal University of São Paulo. Enrollment is listed as 55. The record gives a start of 2012-07 and primary completion of 2014-07. These administrative details describe the registered study and do not establish that every enrolled participant contributed a primary-outcome measurement.

The intervention was cholecalciferol and the comparator was placebo. The study description specifies cholecalciferol at 100,000 IU/week for 12 weeks, while the placebo arm description specifies 100 drops/week for 12 weeks. The intervention is described as a drug in both arm records. The registry characterizes the allocation as randomized and the model as parallel, meaning participants were assigned to one of the treatment groups rather than receiving each treatment in sequence.

The masking information is not fully consistent within the registry record. Its design fields identify masking as single, while the brief summary calls the study double-blind. The record does not clarify the intended meaning of this difference, who was masked, or whether masking was maintained throughout follow-up. The discrepancy should therefore be noted rather than resolved by inference.

The primary outcome is change from baseline in interleukin-6 at 12 weeks, expressed in pg/mL, with the measure specified as a mean and standard deviation. A secondary outcome is change from baseline in C-reactive protein at 12 weeks. The record indicates three outcome measures overall, but numerical results for these measures are not reported in the registry record. It also does not report the number randomized to each arm for the primary analysis, the analysis population, or participant flow after randomization.

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: Patients that have in use of any vitamin D compounds, glucocorticoids, immunosuppressors, or with history of liver failure, intestinal malabsorption, malignance, autoimmune disease, active infection, positive HIV, peritonitis in the last month or elevated serum ionized calcium (\>1.40 mmol/L) were not included in the study.

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 Change From Baseline in Interleukin-6 at 12 Weeks., measured over 12 weeks.

The registered primary endpoint is change from baseline in interleukin-6 (IL-6) at 12 weeks, measured in pg/mL. IL-6 is a cytokine, and the registry’s rationale places it among immune and inflammatory markers of interest in patients receiving dialysis. The endpoint focuses on a change over the intervention period, rather than only a single measurement at the end of treatment. The record specifies that the outcome is summarized as a mean with standard deviation.

In general, a continuous laboratory measure can help quantify the average change in a biological marker across participants. Comparing changes between randomized groups can describe whether the groups followed different average trajectories during the study. The standard deviation describes variation among individual observations around a group mean; it is not itself a measure of how precisely the mean or the between-group contrast has been estimated. A confidence interval, if reported, would be needed to characterize uncertainty around an estimate.

The registry record does not provide the IL-6 values at baseline or follow-up, the mean change in either arm, a between-group estimate, a confidence interval, or a test result. It is therefore not possible from the registry record to describe the observed size or direction of the primary endpoint contrast, or its statistical precision. The rationale for measuring IL-6 does not substitute for those results and does not establish a clinical effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group comparison of cholecalciferol and placebo. Randomization is intended, in general, to create groups that are comparable on average at the point of assignment, including with respect to measured and unmeasured characteristics. It does not guarantee identical groups in a particular trial, especially when group sizes are limited. The record does not report the sequence-generation procedure, concealment method, or detailed allocation process.

What does the primary outcome measure?

The primary endpoint is change from baseline in IL-6 at 12 weeks, in pg/mL. A change score compares a participant’s measurement at follow-up with that participant’s baseline measurement. In general, comparing change between randomized arms targets a difference in the average change during the specified period. It is distinct from comparing only the final measurements, though different statistical models can address the same clinical question under different assumptions. The registry does not state which model or test was used.

The outcome is specified as a mean with standard deviation. The mean describes the central level of a continuous measure, and the standard deviation describes the amount of variation across observations. These summaries do not provide the uncertainty of the estimated treatment contrast. A standard error or confidence interval would convey information about precision, but neither is reported for the primary outcome in the registry record.

How should uncertainty be understood?

General statistical context: an estimate is the value calculated from the observed participants, while a confidence interval expresses uncertainty about the underlying quantity under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, all else equal. Statistical significance and clinical importance are different questions: a test result alone does not state whether a difference matters clinically, and the registry does not provide a threshold for a meaningful IL-6 change. In this record, there is no estimate or interval to interpret.

A p-value is also not a measure of effect size, the probability that a treatment works, or the probability that the null hypothesis is true. It is interpreted relative to a statistical model and a null hypothesis. Because the registry record does not give a primary-outcome p-value or model, none can be assessed. Absence of a posted p-value is not evidence that the comparison was statistically significant or nonsignificant.

What assumptions are relevant?

General statistical context: methods for comparing continuous outcomes commonly rely on assumptions about the outcome distribution, the variance structure, independence of observations, and the form of the model. If measurements are strongly skewed or contain influential observations, a mean-based comparison may not fully describe the data. If variability differs between arms, methods that assume equal variance may give misleading uncertainty estimates. The record does not report distribution checks, transformations, robust methods, or other diagnostics, so the appropriateness of any particular method cannot be evaluated.

Repeated measurements also require attention to the relationship between baseline and follow-up values. A change-score analysis and a model adjusting for baseline can produce different estimates and precision, depending on the data and assumptions. General statistical context: baseline adjustment can account for prognostic information in baseline measurements, but the planned approach must be specified to interpret an estimate. The registry does not report whether the primary analysis used change scores directly, adjusted for baseline, or used another repeated-measures method.

How should the planning illustrations be read?

The registry describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not trial results or evidence of achieved power. The record does not include the numerical planning values or a reported observed effect in the primary results. A planning illustration cannot establish the probability that this completed trial detected an effect, and it is not an observed-power calculation.

General statistical context: planning calculations depend on a target effect, variability, type I error rate, allocation, and analysis method. If the target effect is smaller, more participants are generally required for a given precision or power under otherwise comparable assumptions. This relationship helps explain why planning scenarios may vary across assumed effects. It does not show that a particular sample size is adequate unless the inputs and design are documented. The record does not report the original sample-size justification, so it cannot be determined whether the planning assumptions described in the registry match the trial’s original design rationale.

The brief summary describes measurements in serum and monocytes, alongside the primary IL-6 endpoint. General statistical context: multiple markers, time points, or analyses can raise multiplicity concerns because examining many results increases the chance of finding apparently notable results by chance if no adjustment or hierarchy is specified. The record does not describe an adjustment strategy or a complete analysis plan. The implications cannot be assessed from outcome names alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome as change from baseline in IL-6 at 12 weeks and a secondary outcome of change from baseline in C-reactive protein at 12 weeks. It also describes measurements of 25(OH)D, cathelicidin, IL-6, TNF-α, and related markers in serum or monocytes. The record indicates three outcome measures overall, but does not provide a full analysis plan, list all outcome-specific hypotheses, or report whether any multiplicity adjustment was planned or used.

General statistical context: when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase if each is assessed independently at the same threshold. Approaches to this issue may include defining one primary outcome, controlling an error rate, or treating secondary findings as exploratory. The registered primary outcome identifies a focal question, but does not by itself establish how analyses of the other measures were handled. No conclusion about multiplicity adjustment can be drawn from the registry record.

The record does not report the number of participants with an IL-6 measurement at baseline or 12 weeks, reasons for missing observations, withdrawals by arm, or methods for handling missing data. It also does not state whether the primary analysis followed an intention-to-treat principle, used a per-protocol population, or applied another definition. These omissions prevent assessment of whether the analyzed groups remained comparable after randomization or how incomplete follow-up might affect the estimate.

General statistical context: complete-case analysis can be biased when inclusion in the analysis is related to outcomes or treatment assignment. Methods such as imputation or likelihood-based analysis require assumptions about the missingness process and should be described. Without participant flow, missingness reasons, and analysis methods, the robustness of any result cannot be evaluated. In this case, numerical primary results are also absent, so the effect of missing data on an estimate cannot be examined.

11. 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 0% reporting threshold.

The registry’s serious and other adverse-event figures list 18 participants at risk in the placebo group and 20 in the cholecalciferol group. It records zero serious adverse events and zero other adverse events for both groups. These are the figures entered in the adverse-event record. The deaths fields are null, so deaths are not reported in the registry record.

These entries should be read as registry counts, not as proof that no adverse events occurred in any broader sense. The record does not provide event descriptions, collection methods, observation duration for safety, or an explanation of how the at-risk counts relate to the enrollment figure. It does not report whether the counts reflect all randomized participants, only those who received treatment, or another safety population. No serious adverse-event terms are listed.

General statistical context: adverse-event counts describe events observed and recorded under the trial’s collection procedures. Small counts, limited follow-up, and incomplete reporting can constrain what can be inferred about uncommon events. Zero recorded events does not establish zero risk, and these figures do not establish a comparative safety profile. The registry entries should therefore be interpreted narrowly, without extrapolating beyond the recorded counts or assuming that missing details indicate absence of events.

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

The registry record documents a randomized phase 2 trial of cholecalciferol versus placebo in dialysis patients with hypovitaminosis D. It identifies change from baseline in IL-6 at 12 weeks as the primary endpoint and lists C-reactive protein change as a secondary outcome. These details define the study question and the type of evidence it was designed to collect.

The record does not report the primary endpoint estimates, group-specific changes, a treatment contrast, confidence interval, or p-value. Therefore, it cannot show the direction, magnitude, or precision of the IL-6 comparison. The same limitation applies to the listed secondary outcome and the other immunological markers described in the summary. The trial’s completed status does not fill this reporting gap.

General statistical context: a biomarker outcome can be useful for studying biological response, but a change in a marker is not by itself a direct measure of a clinical outcome. The registry frames this study around immunological markers, and it does not report infection outcomes as a trial endpoint in the listed results. The rationale connecting vitamin D and immune activity should not be mistaken for evidence of a clinical benefit or harm.

The serious and other adverse-event entries record zero events in the listed groups, with deaths not reported in the registry record. Those entries describe only what is posted and do not establish that risk is absent. Details about event ascertainment, safety populations, and follow-up are not reported.

The appropriate conclusion is limited: the registry documents the design, intended comparison, and primary marker, but not the numerical results needed to judge the observed treatment contrast. No claim about whether cholecalciferol changed IL-6 or other markers can be supported from these registry entries alone. Assessing the result would require outcome estimates and their uncertainty, as well as information about the analysis population, missing data, and analysis methods.

13. Why This Trial Matters Statistically

This trial is statistically notable for posing a focused comparison of a continuous immune marker in a randomized parallel-group design. Its primary endpoint is explicitly defined as mean change in IL-6 from baseline at 12 weeks, with a specified unit and summary measure. A clearly identified endpoint helps distinguish the main question from the several other markers discussed in the registry summary.

The registry also illustrates why design details and outcome results need to be read separately. Randomization and a placebo comparator describe how the comparison was intended to be conducted; they do not reveal the estimated difference or its precision. Likewise, a completed status and an enrollment figure do not show how many observations entered the endpoint analysis. In general, transparent reporting of estimates, uncertainty, participant flow, and analysis methods is necessary to interpret a randomized trial fully.

The record’s internal difference between single masking in the design field and double-blind wording in its summary is another relevant reporting detail. Without clarification, readers cannot determine which participants or study personnel were masked. This is a limitation in describing the design, not evidence that masking failed.

Finally, the registry notes planning assumptions for sample-size illustrations but does not report the original sample-size justification or numerical outcome results. General statistical context: planning assumptions answer questions about what effects a design is intended to detect, while observed estimates answer what the collected data indicate. Keeping those concepts distinct prevents planning scenarios from being treated as proof of achieved power or as trial findings. In this record, the distinction is especially important because the primary-outcome estimates are not reported.

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 central limitation for interpreting this trial from the registry record is that numerical results for the primary endpoint are not reported. There are no arm-specific IL-6 changes, between-group estimate, measure of uncertainty, or test result. The record also does not provide numerical results for the listed secondary outcome or the other markers described in the study summary. The observed direction and size of any comparison therefore cannot be assessed.

Other key reporting details are absent. The number randomized to each arm for the primary analysis, participant flow, outcome availability, withdrawals, missing-data reasons, and analysis population are not reported in the registry record. The statistical model, baseline-adjustment approach, assumptions, and sensitivity analyses are also not reported. These omissions limit evaluation of precision, bias, and robustness.

The masking description differs within the record: a design field says single, while the brief summary says double-blind. The record does not explain the discrepancy or identify which roles were masked. It also does not report the original sample-size justification or numerical planning results. Accordingly, the listed planning assumptions cannot be used to infer what the trial was originally designed to detect.

Safety interpretation is limited by the absence of detail about event collection, observation period, and the population represented by the at-risk counts. Deaths are not reported in the registry record. The trial summary discusses hemodialysis and peritoneal dialysis, but subgroup results are not reported. No further conclusions about these limitations can be drawn from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Supplementation With Cholecalciferol in Dialysis Patients — NCT01974245.
• Registry record last updated 2025-03-14; status last verified 2025-02.
• Results first posted 2014-12-12.
• 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.

18. Record Summary

NCT01974245 is listed as a completed randomized phase 2 parallel-group trial sponsored by Federal University of São Paulo, with enrollment of 55. It compares cholecalciferol with placebo in dialysis patients with hypovitaminosis D. The study description specifies cholecalciferol 100,000 IU/week for 12 weeks and placebo 100 drops/week for 12 weeks.

The primary endpoint is change from baseline in IL-6 at 12 weeks, measured in pg/mL and summarized as a mean with standard deviation. Change in C-reactive protein at 12 weeks is listed as a secondary outcome. Numerical outcome results and analysis details are not reported in the registry record. The masking field says single, whereas the brief summary says double-blind. Serious and other adverse-event entries list zero events in both groups; deaths are not reported in the registry record.