Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients (NCT00420290), a randomized na study. The primary outcome is High Sensitivity C-reactive Protein (hsCRP).

2. Clinical Question

The clinical rationale recorded for the study concerns chronic inflammation and uremic wasting in hemodialysis patients. The registry summary describes inflammation as one of several factors thought to be associated with wasting and notes the hypothesized relationship of interleukin 1 beta to protein catabolism. The trial's primary outcome focuses on hsCRP, rather than directly measuring muscle loss, hospitalization, mortality, or uremic wasting. Those broader clinical concerns motivate the question but are not the primary endpoint being compared.

The registry lists Interleukin-6, serum prealbumin, serum albumin, and lean body mass as secondary outcomes. Their names indicate additional biological and body-composition measures, but the results for these outcomes are not reported in the registry record in the registry record for this analysis. The primary statistical comparison is therefore the month 1 hsCRP result.

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group trial of Kineret and placebo. It lists the trial status as completed, the condition as end stage renal disease, and the sponsor as Vanderbilt University. Phase is recorded as not applicable. Enrollment is listed as 31. Enrollment is a registry-level trial figure; it is not the same as the number included in the primary outcome analysis.

The primary endpoint description says the analysis was per protocol and based on participants who completed the 4-week study. The posted group summaries each contain 7 analyzed participants: the Kineret group mean was 4.67 mg/dl, with a standard deviation of 2.87, and the placebo group mean was 15.11 mg/dl, with a standard deviation of 10.18. These are the analysis group sizes and summaries for the primary outcome, not a complete account of participant flow. The numbers screened, assigned, withdrawn, or excluded from the per-protocol analysis are not reported in the registry record.

The record identifies the primary outcome timeframe as month 1. It does not give further details about treatment duration, dosing, visit schedules, the randomization procedure, allocation concealment, or the masking roles. The label quadruple-masked conveys that masking was recorded, but which trial roles were masked is not reported in the registry record. The registry's start and primary-completion dates are not needed to interpret the endpoint comparison.

The primary analysis method is listed as ANCOVA. The record does not identify the covariates, model specification, or assumptions used. It also does not report a confidence interval or adjusted effect estimate for this comparison. Those omissions limit how much can be learned from the inferential result beyond the reported p-value.

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: There is a 3-month screening period following enrollment to determine level of inflammation. To be eligible to participate in the intervention phase of the study and be assigned to a group, participants must have three consecutive CRP levels \> 5 mg/L. Although 31 subjects were enrolled, only 22 were eligible to be assigned to a group.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The number of participants for analysis was based on those subjects who completed the 4-week study. The analysis was per protocol.

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 High Sensitivity C-reactive Protein (hsCRP), measured over month 1.

The primary endpoint is high-sensitivity C-reactive protein (hsCRP) at month 1, measured in mg/dl and summarized as a mean with a standard deviation. The registry describes hsCRP as a sensitive laboratory assay for serum C-reactive protein, a biomarker of inflammation. It is used in this trial to quantify an inflammatory marker, fitting the study's stated interest in inflammation among chronic hemodialysis patients.

A biomarker is a measured biological characteristic. It can help characterize a biological process, but a biomarker result is not itself a direct measure of every health outcome that might matter to patients. In this study, hsCRP does not directly measure muscle mass, nutritional status, hospitalization, or survival. Lean body mass and several serum measures are listed as secondary outcomes, but their results are not reported in the registry record.

The mean describes the average observed hsCRP value in each analyzed group. The standard deviation describes the spread of individual measurements around that group mean; it is not a confidence interval and does not directly quantify the precision of the estimated mean. The reported mean was 4.67 mg/dl in the Kineret group and 15.11 mg/dl in the placebo group, with standard deviations of 2.87 and 10.18, respectively. These summaries describe the per-protocol analysis population at month 1.

The timeframe is recorded as month 1, and the analysis population is described as participants completing the 4-week study. The registry does not report whether hsCRP was also measured at other times or how repeated measurements, if any, were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: hsCRP is measured on a numeric scale, and the registry summarizes it with a mean and standard deviation. For a continuous outcome, a group comparison can be expressed as a difference in means. The registry's posted group summaries are descriptive, while its inferential analysis is identified as ANCOVA. The record does not report an adjusted effect estimate, so the size of the ANCOVA contrast cannot be stated from the registered result.

What does ANCOVA do?

In general, analysis of covariance (ANCOVA) compares group outcomes while accounting for one or more additional variables included in the model. When appropriate baseline or prognostic variables are included, adjustment can improve precision or account for differences in those variables. The adjusted comparison depends on which variables were selected, how they were measured, and how they entered the model. In this trial, those details are not reported in the registry record. It is therefore not possible to describe what the reported ANCOVA adjusted for or reproduce its adjusted estimate from the listed group means and standard deviations.

Randomization and covariate adjustment serve different roles. Random assignment is intended to make treatment groups comparable on average, while model adjustment may account for selected measured characteristics. The record identifies randomized allocation and ANCOVA, but does not provide enough detail to assess the implementation of either procedure beyond those labels. No specific baseline measurements or model diagnostics are reported for the primary result.

What does the p-value tell us?

In general, a p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. Smaller values indicate that the observed data would be less expected under that null model. A p-value does not measure the probability that the null hypothesis is true, the probability that the result will replicate, or the size of an effect. The registry reports p = 0.008 for the ANCOVA comparison. It does not report a confidence interval or adjusted estimate to show the effect's magnitude and precision.

Why is a confidence interval useful?

In general, a confidence interval gives a range of effect estimates compatible with the data and the interval procedure. It conveys precision as well as the direction of an estimated contrast. An interval for a treatment contrast could help readers judge which effect sizes remain reasonably compatible with the trial data. No confidence interval is reported for the primary ANCOVA result. The listed standard deviations are not substitutes: they describe dispersion of individual hsCRP values within each group, not uncertainty around the between-group effect.

How should the group summaries be read?

The Kineret group mean was 4.67 mg/dl, with standard deviation 2.87, and the placebo group mean was 15.11 mg/dl, with standard deviation 10.18. These are unadjusted descriptive summaries for the analyzed participants. They do not account for any covariates that may have been used in ANCOVA. A simple unadjusted re-calculation would require enough information to derive an unadjusted contrast and its uncertainty, but such values are not reported as estimable in the registry record. The reported ANCOVA result should not be conflated with a re-calculated unadjusted comparison.

Why does analysis population matter?

In general, an intention-to-treat analysis retains participants in the groups to which they were randomized, regardless of adherence or completion, while a per-protocol analysis focuses on participants meeting specified protocol conditions. The registry describes this endpoint analysis as per protocol among participants completing the 4-week study. Per-protocol analyses can be vulnerable to bias if completion or adherence is related to prognosis or outcome. Whether that occurred cannot be determined from the posted information. The record does not report an intention-to-treat estimate, the reasons for non-completion, or details of how protocol adherence was defined.

General statistical interpretation also depends on model assumptions, such as an appropriate model form and adequate handling of outcome variability. The registry does not report diagnostics or assumption checks. The standard deviation in the placebo group is larger than in the Kineret group, but that fact alone does not establish a model violation. The distribution of individual measurements and the analysis diagnostics are not reported.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Kineret", "Placebo")
n   <- c(7, 7)
m   <- c(4.67, 15.11)
sp  <- c(2.87, 10.18)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Kineret  7  4.670  2.870  2.016  7.324
CARM  Placebo  7  15.110  10.180  5.695  24.525

11. Analyses Reported by the Sponsor

The sponsor-reported primary analysis is ANCOVA, with p = 0.008. The registry also posts group means and standard deviations for the per-protocol analysis: 4.67 mg/dl with standard deviation 2.87 for Kineret, and 15.11 mg/dl with standard deviation 10.18 for placebo. The descriptive summaries show a lower observed mean in the Kineret group, while the ANCOVA p-value reports the result of the sponsor's adjusted analysis.

An adjusted ANCOVA result and an unadjusted comparison of group summaries are not necessarily identical. Their estimates can differ because ANCOVA may account for covariates, but the covariates and adjusted effect estimate are not reported in the registry record. A recalculated unadjusted contrast and confidence interval are also not reported as estimable for this continuous two-arm comparison. It is therefore not possible to compare numerical adjusted and unadjusted effect estimates or assess whether they align in magnitude.

The record does not flag a discrepancy between the posted analysis and a recalculation. The sponsor's reported p-value is the available inferential result; the available group summaries provide descriptive context, not an independent reconstruction of the ANCOVA. Since the adjusted estimate and confidence interval are absent, the p-value cannot convey the treatment contrast's magnitude or precision on its own.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists hsCRP as the primary outcome and four secondary outcomes: Interleukin-6, serum prealbumin, serum albumin, and lean body mass. It also records 5 outcome measures and 5 analyses. Results for the secondary outcomes are not reported in the registry record. The reported p-value of 0.008 pertains to the primary ANCOVA comparison as recorded; the presence of multiple outcomes makes it relevant to ask whether the analysis planned or adjusted for multiplicity.

In general, testing multiple outcomes can increase the chance of obtaining at least one apparently unusual result even when none of the underlying effects is present. A prespecified primary outcome can help focus interpretation, while an adjustment procedure or a clear hierarchy can address multiplicity. Whether the trial specified such a strategy, and whether any adjustment was applied, is not reported in the registry record. No interim analyses or broader statistical analysis plan details are reported, so none should be inferred.

The primary analysis population is described as per protocol and based on those who completed the 4-week study. The group summaries list 7 participants for Kineret and 7 for placebo. Enrollment is listed as 31, but the registry entries do not describe the path from enrollment to the primary analysis population. Numbers randomized by arm, exclusions, discontinuations, missing endpoint measurements, and reasons for missingness are not reported in the registry record.

In general, missing data can affect both precision and validity, depending on why values are missing and how the analysis handles them. Restricting analysis to completers can produce groups that differ from the randomized groups if completion is related to treatment or outcome. The available record does not establish whether this happened, and it does not describe imputation or sensitivity analyses. An intention-to-treat analysis is not reported for the primary endpoint. Therefore, readers cannot assess from the registry result whether the per-protocol finding is robust to missing outcomes or deviations from assigned treatment.

13. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry reports no serious adverse events among the 7 Kineret participants at risk and no serious adverse events among the 7 placebo participants at risk. It records other, non-serious adverse events for 4 Kineret participants and 3 placebo participants. These figures are descriptive counts for the reported safety groups; they do not establish whether an event was caused by the assigned intervention.

No deaths are listed for either group. The death values are not reported in the registry record, so they should not be interpreted as confirmed zero deaths. The record also lists no top serious adverse event terms. That absence of listed terms is consistent with the posted serious-event counts, but it does not provide further detail about the types or severity of non-serious events.

Safety findings depend on the number of participants followed, the duration and completeness of follow-up, how events were defined and collected, and whether all events were reported. The registry entries do not provide event descriptions, exposure duration, follow-up completeness, or a detailed adverse-event analysis plan. The observed counts therefore offer limited descriptive information and should not be used to infer that rare harms were excluded or that the groups had equivalent safety.

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

The result describes hsCRP measurements among participants included in a per-protocol analysis after completing the 4-week study. The posted mean was lower in the Kineret group than the placebo group, and the sponsor-reported ANCOVA comparison had p = 0.008. Together, those details indicate that the registry reports a difference in the primary biomarker outcome under the stated analysis. They do not supply the adjusted effect size or its confidence interval.

Statistical evidence and clinical meaning are not interchangeable. A p-value does not indicate how large the group contrast was, whether it is important to patients, or whether it would be reproduced in another setting. A confidence interval and a clear adjusted estimate would help characterize magnitude and precision, but neither is reported in the registry record. The group means give descriptive values in mg/dl, while the standard deviations show variability among analyzed participants.

hsCRP is an inflammatory biomarker. A difference in this marker does not directly demonstrate a change in muscle mass, nutritional state, hospitalization, mortality, or other clinical outcomes. The registry lists lean body mass and serum measures as secondary outcomes, but their results are not reported in the registry record. The broader rationale concerning inflammation and uremic wasting should therefore be distinguished from what the primary outcome directly measures.

The analysis is limited to participants described as completing the study and analyzed per protocol. Without participant-flow details, missing-data methods, or an intention-to-treat result, the effect of exclusions and non-completion cannot be evaluated. The result also cannot be fully appraised for model adjustment because ANCOVA covariates and diagnostics are not reported. The most precise reading is consequently narrow: the analyzed groups had the posted hsCRP summaries, and the registry reports a statistically notable ANCOVA result, but the adjusted magnitude, uncertainty, and broader clinical implications remain unclear.

15. Why This Trial Matters Statistically

This trial is statistically interesting because it combines a small per-protocol analysis population with a continuous inflammatory biomarker and a reported covariate-adjusted comparison. The group summaries make the observed outcome scale concrete, while the ANCOVA p-value shows that the registry reports an inferential analysis beyond descriptive means. At the same time, the adjusted estimate and confidence interval are absent, leaving an important gap between evidence against a null model and the size and precision of the comparison.

The difference between enrollment and the analyzed population is also important. Enrollment is recorded as 31, while the primary endpoint summaries list 7 participants in each group. The analysis description says that participants who completed the 4-week study were included per protocol. Without a participant-flow account, readers cannot determine how many were assigned, why some were not analyzed, or whether exclusions affected the randomized comparison. This illustrates why the analysis population and missing-data approach are central parts of trial interpretation, not minor reporting details.

The trial also shows why a biomarker result should be kept distinct from a patient-important outcome. hsCRP measures an inflammatory marker, while the study rationale discusses wasting and the record lists other biological and body-composition outcomes. The available primary result can address the reported biomarker comparison, but it cannot by itself answer whether broader clinical outcomes changed. Results for the secondary measures are not reported in the registry record.

Finally, multiplicity, model specification, and precision matter alongside the p-value. The record lists multiple outcomes, identifies ANCOVA, but does not report the adjustment variables, multiplicity strategy, or an effect confidence interval. These omissions do not erase the reported result; they define what can responsibly be concluded from it.

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 reporting gaps limit interpretation. The primary result is based on a per-protocol population of participants who completed the 4-week study, with 7 analyzed in each group. The registry enrollment figure is 31, but participant flow from enrollment through assignment and endpoint analysis is not reported in the registry record. Reasons for non-completion or exclusion, and whether these differed by assigned group, are not reported.

The registry identifies ANCOVA but does not report its covariates, model specification, assumption checks, adjusted group contrast, or confidence interval. The p-value alone cannot supply the missing estimate or quantify its precision. Although group means and standard deviations are posted, they do not reproduce a covariate-adjusted comparison. No unadjusted two-arm estimate is reported as estimable for the primary continuous outcome.

Multiplicity procedures are not reported despite the listing of secondary outcomes. The registry does not report results for those secondary measures, nor does it describe whether outcome testing followed a prespecified hierarchy or adjustment strategy. Missing-data methods and an intention-to-treat result are also not reported. Thus, the robustness of the per-protocol result to missing measurements or exclusions cannot be assessed from the registry record.

Details of randomization, allocation concealment, dosing, treatment adherence, the specific roles covered by quadruple masking, follow-up completeness, and endpoint collection are not reported in the registry record for this analysis. These are not proof of deficiencies in conduct; they are limits on what can be evaluated from the registry information. The safety summary similarly lacks event descriptions and detailed follow-up information. The findings should consequently be interpreted as a reported short-term biomarker comparison in the analyzed participants, not as a complete account of efficacy, safety, or clinical outcomes.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Inflammation, Proteolysis and IL-1 Beta Receptor Inhibition in Chronic Hemodialysis Patients — NCT00420290.
• Registry record last updated 2011-11-17; status last verified 2011-10.
• Results first posted 2011-11-17.
• 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

NCT00420290 is a completed, randomized, quadruple-masked, parallel-group trial sponsored by Vanderbilt University, listed for end stage renal disease. It compares Kineret, described as an interleukin-1 receptor antagonist, with placebo. Enrollment is listed as 31.

The primary endpoint is mean hsCRP in mg/dl at month 1. The registry describes a per-protocol analysis of participants who completed the 4-week study. The Kineret group had a mean of 4.67 and standard deviation of 2.87 among 7 analyzed participants; the placebo group had a mean of 15.11 and standard deviation of 10.18 among 7 analyzed participants. The reported analysis is ANCOVA with p = 0.008. An adjusted effect estimate and confidence interval are not reported in the registry record.

Four secondary outcomes are listed, but their results are not reported in the registry record. Serious adverse events were recorded for neither group; other adverse events were recorded for 4 participants in the Kineret group and 3 in the placebo group. Death counts are not reported in the registry record.