Sodium Chloride and Protein-Bound Toxin Removal in Hemodiafiltration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sodium Chloride and Protein-Bound Toxin Removal in Hemodiafiltration (NCT01923961), a randomized na study. The primary outcome is Removal of Para-cresylsulfate.

2. Clinical Question

The study concerns removal of a protein-bound uremic toxin during dialysis. The registry’s stated rationale is that increasing the free fraction of a protein-bound toxin may allow more of it to be removed. The comparison therefore describes the recorded reduction ratio under three treatment conditions, including hemodiafiltration with increased sodium chloride concentration in the infusion fluid.

The posted results give a mean reduction of 42.0 for hemodiafiltration with NaCl infusion, 32.6 for hemodialysis, and 33.6 for standard hemodiafiltration. These are descriptive results. The registry record does not report a formal test or confidence interval establishing how precisely the conditions differ. The values alone do not answer whether the observed pattern would persist in a larger or different group.

3. Trial Design

This was a randomized, unmasked, crossover trial with an enrollment of 8. Its listed phase is NA, and its status is completed. The condition is end-stage renal disease. EXcorLab GmbH is listed as the sponsor. The recorded study start is 2013-08, and primary completion is 2015-03-30.

A crossover design exposes participants to more than one treatment condition, allowing measurements under different conditions to be made within the same participant. The registry describes three treatment sequences: one begins with hemodiafiltration with NaCl infusion, one with hemodialysis, and one with standard predilution hemodiafiltration. Each sequence includes all three conditions. The treatment periods are described as 4 hours, with a washout period of 1 week between periods.

Randomization applies to assignment to the treatment sequences; the record does not state how sequence allocation was generated or whether it was balanced. Masking is listed as none. The record does not report further details of the randomization procedure, allocation concealment, or the rationale for the washout period. These omissions limit how fully the conduct of the crossover can be assessed from the registry entry.

The reported outcome is summarized for 8 participants in each treatment condition. In a crossover study, those condition counts should not be read as independent groups of different people: the sequence descriptions indicate that the same enrolled participants were intended to receive each condition. The posted summary does not provide participant-level measurements or a model accounting for within-participant dependence, treatment order, or period.

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.

First Intervention

Washout (1 Week)

Second Intervention

Washout (1 Week)

Analysis population for the primary outcome, as defined in the registry: Per protocol population

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 Removal of Para-cresylsulfate, measured over 4 hours.

The primary endpoint is removal of para-cresylsulfate, reported as a percentage reduction over 4 hours. The registry describes the reduction ratio as based on the plasma solute concentration at baseline and at the end of the intervention. A higher percentage reduction represents a larger observed fall between those two measurements; it does not, by itself, describe the absolute plasma concentration or the amount removed from the body.

Para-cresylsulfate is identified in the trial title and summary as a protein-bound uremic toxin. The registry’s rationale is that increasing the toxin’s free fraction might allow greater removal during dialysis. Measuring its plasma reduction provides an endpoint for comparing the biochemical response recorded during the different treatment conditions.

The posted outcome is a continuous measure, summarized as a mean with standard deviation. The reported means are 42.0 for hemodiafiltration with NaCl infusion, 32.6 for hemodialysis, and 33.6 for standard hemodiafiltration. The standard deviations are 22.1, 18.5, and 16.1, respectively. The registry does not report confidence intervals for these means or a formal estimate of the within-participant contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry posts continuous outcome summaries for three treatment conditions. The main descriptive statistics are the mean reduction ratio and its standard deviation. No formal analysis results are listed for the primary outcome, and the registry record does not describe a statistical analysis plan.

What does the mean describe?

A mean is the arithmetic average of the recorded outcome values in a group. For this endpoint, it represents the average percentage reduction in plasma para-cresylsulfate across the participants included in that condition’s summary. The posted means are 42.0 for hemodiafiltration with NaCl infusion, 32.6 for hemodialysis, and 33.6 for standard hemodiafiltration. A mean is a useful compact description, but it can conceal variation among participants and does not indicate how certain the estimated average is.

What does the standard deviation describe?

The standard deviation describes how dispersed individual measurements are around the mean. The posted standard deviations are 22.1, 18.5, and 16.1, in the same treatment order. A larger standard deviation indicates more spread in the observed measurements. It is not a confidence interval and does not measure uncertainty in the mean in the same way. General statistical principle: the standard deviation concerns variation among observations, while a confidence interval concerns uncertainty about an estimated quantity.

Why does the crossover structure matter?

In a crossover study, a participant can contribute measurements under multiple treatment conditions. The resulting observations are related because measurements from the same participant may share characteristics. General statistical principle: an analysis that treats related measurements as independent can misrepresent uncertainty. A suitable crossover analysis commonly accounts for the paired nature of the data and may also consider treatment period and sequence. The registry record does not report the analysis method used for these issues, and no formal comparison is posted.

The sequence descriptions include washout periods between treatments. A washout is intended to separate treatment periods, but its adequacy depends on the outcomes and interventions being studied. The registry record does not report a washout justification or evidence assessing carryover. It also does not report a model specification, assumptions about carryover, or a test of treatment-by-period effects. These details cannot be inferred from the fact that the design is labeled crossover.

How should the absence of inferential results be read?

A confidence interval gives a range of values compatible with an estimate under the assumptions of the analysis; narrower intervals generally indicate greater precision. A p-value is a measure calculated under a specified statistical model and null hypothesis, not the probability that the null hypothesis is true. Neither a confidence interval nor a p-value for a comparison is reported in the registry record. The group means and standard deviations therefore support descriptive reading, but they do not quantify the precision of a contrast or provide a formal test of the stated treatment question.

The analysis listings indicate 0 analyses, while the registry does post descriptive values for the primary outcome. This distinction matters: reported summaries are not equivalent to a reported inferential analysis. The record does not state whether the study team conducted analyses that were not entered into the registry. It also does not specify whether comparisons were adjusted for the crossover structure or whether any covariates were included.

What do the planning assumptions mean?

The planning illustrations use the observed effect as a starting point, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The intended effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence about the precision of the completed study. Sample-size planning values describe participants per arm for a specified design and target; they are not observed power and do not alter the uncertainty in the results from the 8 enrolled participants.

General statistical principle: power is a design-stage probability tied to assumptions about an effect, variability, significance level, and sample size. It is not a retrospective measure of whether a result is convincing. The registry does not report the trial’s own sample-size justification, and the planning illustrations are not identified as the study’s original design basis. The record also does not provide a detailed method for translating the crossover outcome into the two-arm planning assumptions. Those illustrations should therefore be interpreted as planning scenarios rather than as an explanation of the trial’s enrollment.

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("Hemodiafiltration, NaCl Infusion", "Hemodialysis", "Hemodiafiltration")
n   <- c(8, 8, 8)
m   <- c(42, 32.6, 33.6)
sp  <- c(22.1, 18.5, 16.1)
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  Hemodiafiltration, NaCl Infusion  8  42.000  22.100  23.524  60.476
CARM  Hemodialysis  8  32.600  18.500  17.134  48.066
CARM  Hemodiafiltration  8  33.600  16.100  20.140  47.060

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and identifies two secondary outcomes: plasma sodium concentrations and hemocompatibility. It does not report how many hypotheses were tested, how outcomes were prioritized beyond the designation of the primary endpoint, or whether any adjustment for multiple comparisons was planned. Multiplicity refers generally to the increased chance of at least one false-positive finding when several hypotheses are tested. Whether that issue affected this study’s analysis cannot be determined from the registry record.

The analysis listings indicate 0 analyses. The record nevertheless contains descriptive group summaries for the primary outcome. It does not report inferential results for that endpoint or for the secondary outcomes. The posted secondary outcome names do not establish that results were collected or analyzed, and their numerical results are not reported in the registry record.

The primary outcome is described for the per protocol population. The registry record does not explain how that population was defined, whether any enrolled participants were excluded from it, or how deviations from the planned treatment sequence were handled. Missing outcome data, withdrawals, and imputation methods are not reported in the registry record. Although the enrollment is 8 and each listed condition has 8 participants, those counts do not establish that every planned measurement was available or that no data were missing.

For a crossover trial, missing observations in one period can affect within-participant comparisons differently from missing data in a parallel-group study. General statistical principle: the consequences depend on why data are missing and how the analysis handles incomplete participant records. The registry does not report this information, so the influence of missingness on the posted summaries cannot be assessed.

12. 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.

The registry reports zero serious adverse events among 8 participants at risk for each of the three treatment conditions: hemodiafiltration with NaCl infusion, hemodialysis, and standard hemodiafiltration. It also reports zero other adverse events among 8 participants at risk in each condition, and zero deaths in each group. No serious adverse event terms are listed.

These are event counts in a small study, not proof that an intervention has no safety risks. In a crossover design, participants may be exposed to multiple conditions, so the group entries should not automatically be interpreted as independent sets of participants. The record does not describe the method used to attribute events to a treatment period, nor does it provide event narratives or information on duration and severity for events that were not reported.

The figures describe what the registry record reports during the study; they do not establish the frequency of uncommon events or predict safety in other populations or settings. Zero reported events should be read as no events entered in these categories for the listed groups, rather than as a guarantee that no adverse effects can occur.

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

The registry supports a descriptive account of para-cresylsulfate reduction across three dialysis conditions. The mean reduction was 42.0 with hemodiafiltration and NaCl infusion, 32.6 with hemodialysis, and 33.6 with standard hemodiafiltration. Standard deviations indicate variation around those means, but the registry does not provide confidence intervals or a formal comparison of the conditions.

The results do not establish whether the observed differences are larger than would be expected from sampling variation, whether the pattern would be reproduced, or whether it reflects the proposed free-fraction mechanism. The record does not post a measurement of free fraction as part of the listed primary endpoint. Nor does it report a clinical outcome linked to toxin reduction. A biochemical reduction ratio is a measure of the plasma concentration change described by the registry; it should not be treated as evidence of a patient benefit.

The randomized crossover design is relevant because participants were scheduled to receive each of the conditions, and randomization assigned treatment sequence. However, the small enrollment and lack of a posted inferential analysis mean the registry does not resolve the comparative question with quantified precision. The means are useful as a record of the observed summaries, but they cannot substitute for participant-level analysis that accounts for the within-person structure.

The record also does not report detailed information on missing data, period effects, carryover assessment, or the statistical model. Those omissions make it difficult to judge whether the summaries fully reflect the intended crossover comparison. The results should be understood within those limits, without extending them to conclusions about treatment effectiveness or safety beyond the recorded observations.

14. Why This Trial Matters Statistically

This trial is statistically notable because its crossover structure can make efficient use of within-participant comparisons: each participant is described as receiving all three treatment conditions in a randomized sequence. In general, measuring outcomes repeatedly in the same participant can help distinguish treatment-related variation from stable differences between participants. That advantage depends on appropriate analysis of the related measurements and on adequate handling of sequence, period, and possible carryover effects.

The posted summaries do not show whether those design features were incorporated into an inferential model. The registry gives means and standard deviations for each condition, but no formal comparison, confidence interval, or p-value. This makes the trial a useful example of why descriptive outcome summaries and comparative evidence are not interchangeable. The values show what was recorded on average; they do not quantify uncertainty around the contrast that motivates the study.

The enrollment of 8 also emphasizes the importance of precision. With few participants, individual observations can have a strong influence on a mean, and uncertainty about an average or treatment contrast may remain substantial. General statistical principle: a result can have an apparently clear numerical ordering and still be imprecise. Reporting the paired data and a model aligned with the crossover design would help readers assess the comparison, but those details are not reported in the registry record.

The case also illustrates the distinction between a mechanistic rationale and an outcome result. The trial rationale proposes that sodium chloride concentration could affect the free fraction and removal of protein-bound toxins. The posted primary endpoint addresses plasma para-cresylsulfate reduction, but the registry does not provide a formal analysis testing the comparative question. The rationale gives context for the endpoint; it does not establish the mechanism or clinical meaning of the observed means.

15. 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 small enrollment is a central limitation of this record. The study enrolled 8 participants, and the posted group summaries do not include confidence intervals or participant-level observations. Consequently, readers cannot assess the precision of the means or inspect the distribution of individual responses from the registry entry.

Although the trial is randomized and crossover, important analysis details are not reported in the registry record. These include the method of sequence generation, the crossover model, treatment-period handling, carryover assessment, and the approach to within-participant correlation. The washout period is described as 1 week, but its rationale and adequacy are not reported. No formal comparative analysis is posted.

The primary outcome is reported for the per protocol population, but that population’s definition and its relationship to the enrolled participants are not described. Missing measurements, participant withdrawals, protocol deviations, and methods for handling incomplete records are also not reported. This limits assessment of possible selection or missing-data effects.

The registry names plasma sodium concentrations and hemocompatibility as secondary outcomes, but numerical results for them are not reported in the registry record. It does not describe multiplicity handling or a detailed statistical plan. The absence of these details does not establish that no such procedures existed; it means they cannot be evaluated from the registry entry. The posted adverse-event counts are also limited to the reported categories and do not provide detailed event descriptions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sodium Chloride and Protein-Bound Toxin Removal in Hemodiafiltration — NCT01923961.
• Registry record last updated 2019-01-16; status last verified 2018-07.
• Results first posted 2019-01-16.
• 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.

19. Record Summary

NCT01923961, titled “Sodium Chloride and Protein-Bound Toxin Removal in Hemodiafiltration,” is a completed randomized, unmasked crossover trial sponsored by EXcorLab GmbH. It enrolled 8 participants with end-stage renal disease. The recorded start was 2013-08, and primary completion was 2015-03-30.

The primary endpoint was percentage reduction in para-cresylsulfate over 4 hours, summarized as a mean and standard deviation for the per protocol population. The posted means were 42.0 for hemodiafiltration with NaCl infusion, 32.6 for hemodialysis, and 33.6 for standard hemodiafiltration. No formal comparison or confidence interval is reported in the registry record.

The secondary outcomes listed are plasma sodium concentrations and hemocompatibility. Serious adverse events, other adverse events, and deaths are reported as zero in each listed condition. The registry record does not report detailed missing-data methods, a crossover analysis model, or a sample-size justification for the trial.