Effect of Rifaximine on Sleep Disorders in Patients Suffering From Hepatic Encephalopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Rifaximine on Sleep Disorders in Patients Suffering From Hepatic Encephalopathy (NCT02163837), a na na study. The primary outcome is Percentage of Slow Wave Sleep and REM Sleep.

2. Clinical Question

The study concerns sleep in people with hepatic encephalopathy. Its summary notes sleep disturbances and daytime sleepiness as the motivation for assessing sleep quality, quantity, sleep schemes, and physical activity before and after rifaximine treatment. These are study aims, not findings: the record does not establish that participants experienced a particular change in sleep or activity.

Because this is a single-group study, the question is not a randomized comparison of rifaximine with a control treatment. A before-and-after assessment can describe changes over time among participants, but by itself it cannot distinguish a treatment effect from other explanations for change. Those may include natural variation, changes in other care, measurement variability, or factors related to when the assessments occurred. The record does not report enough detail to evaluate these possibilities.

The registry record names Sleep Efficiency as a secondary outcome and indicates five outcome measures overall. It does not give numerical results for the primary outcome or the named secondary outcome. Thus, the clinical question is clear at the level of the planned measurement, while the posted record does not supply the outcome information needed to estimate what happened.

3. Trial Design

The registry record identifies NCT02163837 as a completed, single-group study sponsored by Centre Hospitalier Universitaire Saint Pierre. Enrollment is listed as 15. The study began in 2014-03 and its primary completion is listed as 2015-07. The phase is listed as NA. Allocation is listed as NA, and masking is listed as NONE.

The study summary describes assessment of sleep quality, quantity, sleep schemes, and physical activity before and after a 2 weeks treatment with rifaximine. Rifaximine is the listed drug intervention. The record does not identify a separate control arm, and its single-group design means it is not a randomized comparison. The arm description is blank. The before-and-after description supplies the broad intent, but details of assessment visits and how measurements were paired for analysis are not reported in the registry record.

The primary outcome is the percentage of total sleep time per 24h spent in slow wave sleep and REM sleep combined, assessed by 24-h polysomnography. The primary outcome timeframe is listed as 28 days. That timeframe and the summary's description of a 2 weeks treatment are both recorded, but the record does not explain how the outcome timeframe relates to treatment or the timing of measurement.

Sleep Efficiency is named as a secondary outcome, and five outcome measures are listed in total. One analysis is listed, but the statistical procedure, analysis population, and handling of repeated measurements are not reported in the registry record. The record is marked completed, but that status does not establish that every planned assessment was collected or that results were posted. Numerical primary and secondary outcome findings are not reported, so the study's design can be described but its measured sleep changes cannot be quantified from this record.

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: all participants of this single arm study were actively enrolled

Before Rifaximin

Day 28 of Rifaximin Treatment

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 Percentage of Slow Wave Sleep and REM Sleep, measured over 28 days.

The primary endpoint combines the percentage of sleep spent in slow wave sleep with the percentage spent in REM sleep during sleep per 24h. It is expressed as a percentage of total sleep time per 24h and assessed by 24-h polysomnography. The registry describes the outcome parameter as a mean with standard deviation.

As a general statistical concept, sleep-stage proportions describe how sleep time is distributed across stages rather than measuring sleep duration alone. Combining the two named stages creates one summary measure of their share of total sleep time. A percentage scale can make that distribution interpretable relative to the recorded total sleep time, but it does not by itself indicate whether a change is important to patients or how it relates to daytime symptoms. Those interpretations require results and supporting clinical context, neither of which is reported in the registry record.

The endpoint is relevant to the study's stated interest in sleep quality and sleep schemes, and polysomnography provides the specified assessment method. However, the record does not report the actual mean, standard deviation, change from baseline, or an interval describing uncertainty. It also does not state the precise assessment schedule. Although the summary describes measurements before and after treatment, the primary timeframe is 28 days and the relation between that timeframe and the 2 weeks treatment is not explained. The registry record therefore identifies what was intended to be measured, but not what was observed or how precisely it was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record specifies a continuous primary outcome summarized as a mean and standard deviation. These are descriptive statistics: the mean locates the center of the observed values, while the standard deviation describes their spread around that center. Neither statistic alone gives the precision of an estimated mean or change. Precision is often conveyed with a confidence interval, but no confidence interval is reported for the primary endpoint in this record.

What does a confidence interval communicate?

In general, a confidence interval describes the uncertainty around an estimate under the assumptions of the statistical method used. A narrower interval indicates greater precision than a wider interval for the same type of estimate. It does not show the range of values for individual participants, and it does not by itself establish clinical importance. For this study, the record does not report an interval for the primary outcome, so its precision cannot be judged.

The primary endpoint is a percentage derived from sleep stages measured by 24-h polysomnography. For continuous outcomes, an analysis may estimate a mean at a visit, a change between visits, or a difference between groups. Those targets are not interchangeable. The summary describes before-and-after assessment, whereas the registry lists one analysis and a 28 days timeframe; it does not state the precise statistical target or method. It would therefore be inappropriate to assume that the analysis was a paired comparison, an independent comparison, or a particular model.

Why does the single-group design matter?

As a general concept, repeated measurements on the same participants can account for the fact that observations from one person are related. A paired method or a model for repeated measurements may be suitable in some settings, depending on the data and design. But the registry record does not report which method was used, whether all participants had measurements at both times, or how the timing of visits was handled. A before-and-after description does not by itself identify the analysis.

Even a well-conducted within-person comparison would estimate change over time in the observed group, not necessarily the causal effect of treatment. Without a concurrent control group, changes unrelated to treatment may contribute to the measured difference. Statistical adjustment cannot automatically remove unmeasured or time-varying influences. The registry record does not report an approach for addressing such influences.

How should uncertainty and statistical significance be read?

As a general explanation, a hypothesis test evaluates how compatible observed data are with a specified null hypothesis under model assumptions. A p-value is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. An effect estimate and its confidence interval are usually more informative about magnitude and precision. No p-value, estimate, or interval for the primary outcome is reported in the registry record, so none can be interpreted for this study.

The record does include a general planning description based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such planning illustrations are not observed power and do not alter the actual design. This study is identified as single-group, not a randomized comparison with equal allocation between arms. The registry record does not report a sample-size justification for the study's own design, nor does it provide the observed effect or a numerical planning result in the details summarized for this record. Accordingly, a hypothetical two-arm planning calculation should not be read as evidence about the study's achieved precision or findings.

For continuous outcomes, planning calculations generally depend on the effect targeted, variability, error rate, allocation, and assumptions of the chosen method. Smaller effects are generally harder to distinguish from random variation than larger effects, all else being equal. These are general statistical relationships; the record does not report the study-specific variability assumptions or a design justification. A planning illustration estimates a recruitment requirement under its assumptions. It does not report how many participants were actually analyzed, and it is not a substitute for a confidence interval around observed data.

What information is missing for reproducing the analysis?

The registry record does not report the primary outcome values, individual-level data, exact analysis procedure, analysis population, missing-data approach, or model assumptions. It also does not report how the standard deviation was used in the analysis, or whether any adjustment was made for baseline values or other covariates. Without these elements, the analysis cannot be independently reconstructed from the record. This is a limit on what can be assessed, not evidence that a particular method was or was not used.

The record lists five outcome measures and one analysis, but does not say which outcomes were included in that analysis or whether the stated analysis covers all planned comparisons. If multiple outcomes or time points are tested, the chance of at least one nominally unusual result can increase. Methods such as prespecifying a primary outcome or adjusting for multiple testing can address particular multiplicity concerns, but the registry record does not report how multiplicity was handled. The primary outcome is identified by title, yet the analysis plan and any adjustment remain unreported.

In general, over-dispersion means that observed variability is greater than expected under a model's assumed distribution. When that assumption is violated, standard errors and inferential results can be unreliable unless the model accounts for the extra variability. This concept is not a claim about these data: the registry record does not provide outcome distributions or model details that would allow over-dispersion to be assessed. More broadly, statistical methods are interpretable only when their assumptions, estimates, and uncertainty are available. Here, the registry record provides the endpoint definition and design context but not the numerical findings needed to evaluate an analysis.

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("Rifaximine")
n   <- c(15)
m   <- c(56)
sp  <- c(16)
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  Rifaximine  15  56.000  16.000  47.139  64.861

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures, names the combined percentage of slow wave sleep and REM sleep as the primary outcome, and identifies Sleep Efficiency as a secondary outcome. It lists one analysis. The other outcome measures and the scope of that analysis are not described in the record. No statistical analysis plan, multiplicity adjustment, or hierarchy among secondary outcomes is reported in the registry record.

In general, when several outcomes or comparisons are examined, the chance of observing an apparently notable result by chance can increase. Prespecifying a primary outcome helps distinguish the principal question from additional analyses, while an adjustment or other planned strategy may address multiple testing. The record identifies a primary outcome, but does not state whether or how additional outcomes and time points were incorporated into the inferential plan. The absence of that information does not establish that no strategy was used.

Missing-data methods are also not reported in the registry record. Enrollment is listed as 15, but the number of participants with usable measurements for each outcome, the reasons for any missing assessments, and the handling of incomplete records are not given. The analysis population is not specified. It is therefore not possible to determine whether the posted analyses, if any, included all enrolled participants or a subset.

As a general matter, missing observations can affect interpretation when the likelihood of missingness relates to participant characteristics or outcomes. Different assumptions and methods can lead to different estimates. Because the record provides neither outcome results nor a missing-data description, the impact of incomplete data cannot be evaluated. These omissions limit assessment of the reliability and reproducibility of any analysis but do not, on their own, prove that data were missing or that an analysis was biased.

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 serious adverse event figures list 15 participants at risk in the rifaximine group and 0 affected by a serious adverse event. The record also lists 15 at risk for other adverse events and 0 affected. Deaths are listed as 0. No top serious adverse event terms are listed.

These figures describe what was recorded for the study group; they are not a comparison with an untreated or active-control group. In a single-group study, the counts cannot estimate how event frequency differs from another treatment or from the absence of treatment. The record does not give event definitions, collection procedures, follow-up completeness, or detailed safety summaries, so the scope of event ascertainment cannot be assessed.

A zero count in a group of this size does not establish that an event cannot occur or that there is no safety risk. It means that the registry record lists no affected participants for the specified categories. It also does not describe non-serious symptoms individually or establish that all participants had complete safety follow-up. The figures should therefore be read as recorded counts, not as proof of absence of harm or as a comparative safety finding.

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

The record identifies a completed, single-group study that enrolled 15 participants and intended to assess sleep measures around rifaximine treatment. Its primary endpoint is defined as the combined percentage of total sleep time spent in slow wave sleep and REM sleep, assessed by 24-h polysomnography, with a 28 days timeframe. These details describe the research question and measurement approach.

The registry record does not report numerical results for that primary endpoint. It therefore does not show the observed mean, change, variability, or uncertainty. Without those values, no conclusion can be drawn from this record about the direction or size of a sleep change. The named secondary outcome, Sleep Efficiency, also has no numerical result reported in the registry record.

Even if a before-and-after change were reported, a single-group study would not by itself establish that rifaximine caused it. Other explanations for change over time cannot be ruled out by a comparison with participants' earlier measurements alone. The absence of a separate control group is therefore central to interpretation, rather than a minor technical detail.

The record also does not report the exact assessment schedule, the analysis method, the analysis population, missing-data handling, or multiplicity strategy. The primary timeframe of 28 days and the summary's 2 weeks treatment duration are both stated, but their relationship is not explained. These gaps make it impossible to evaluate the analysis or the precision and robustness of an estimate.

The safety counts list no serious adverse events, other adverse events, or deaths among the recorded group counts. Those figures are descriptive and do not establish absence of risk, particularly without a comparator and fuller information on event ascertainment. Overall, the record provides useful design and endpoint definitions, but not the outcome results needed to judge sleep changes or their clinical importance.

14. Why This Trial Matters Statistically

This study is statistically notable because it asks a focused measurement question in a design without a randomized control group. The combination of slow wave sleep and REM sleep as a proportion of total sleep time is a defined continuous endpoint, and 24-h polysomnography is the stated assessment method. Making the endpoint and timeframe explicit is important for understanding what an analysis is intended to estimate.

At the same time, the single-group structure illustrates the distinction between documenting change and attributing change to an intervention. A before-and-after observation can describe the course of participants' measurements, but it cannot separate treatment-related change from other influences as effectively as a controlled comparison. Statistical significance, even if reported, would not resolve that design limitation on its own.

The record also highlights why numerical results and uncertainty measures matter. A mean and standard deviation are specified as the outcome summary, but the record does not report their values or an estimate of change. Without an estimate and a measure of precision, readers cannot judge the range of effects compatible with the data. The enrollment count alone cannot replace that information or reveal how many participants contributed complete measurements.

Finally, the record distinguishes a defined primary endpoint from a complete analysis account. Five outcome measures and one analysis are listed, yet analysis methods, missing-data handling, and multiplicity procedures are not described. These features matter because they shape how confidently results can be interpreted and reproduced. The registry entry offers a clear example of why study design, measurement, analysis reporting, and result reporting all contribute to a statistical reading.

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 most immediate limitation for interpreting this study is that the registry record does not report numerical results for the primary outcome. Neither the observed mean nor a change estimate, variability, confidence interval, or test result is available. The named secondary outcome, Sleep Efficiency, is also not accompanied by numerical findings. Thus, the planned endpoint is identifiable, but the observed sleep data cannot be assessed.

The single-group design has no separate control group and is not a randomized comparison. Changes between assessments, if any, could reflect influences other than the intervention. The record's summary describes before-and-after assessment, but does not provide enough detail about visit timing, measurement completion, or the analysis to assess the exact within-group comparison.

The record states a primary timeframe of 28 days and describes a 2 weeks treatment, without explaining how those periods relate. The intervention details are limited to the drug name; dose, schedule, adherence, and concurrent care are not reported in the registry record. Participant eligibility and baseline characteristics are also not described in the registry record recorded.

Enrollment is listed as 15, but the number analyzed for each outcome, participant flow, and reasons for any missing measurements are not reported. Statistical methods, analysis populations, and adjustment for multiple outcomes are not described. These gaps prevent assessment of precision, robustness, and reproducibility. The listed safety counts likewise lack detail on ascertainment and do not provide a controlled safety comparison. Together, these limitations restrict conclusions to the study's stated design and measurement plan, rather than its unreported outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Rifaximine on Sleep Disorders in Patients Suffering From Hepatic Encephalopathy — NCT02163837.
• Registry record last updated 2019-05-01; status last verified 2019-04.
• Results first posted 2019-04-09.
• 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

NCT02163837 is listed as a completed, single-group study sponsored by Centre Hospitalier Universitaire Saint Pierre, with enrollment of 15. The record lists the study start as 2014-03 and primary completion as 2015-07. Phase and allocation are listed as NA, and masking as NONE.

The study summary describes assessing sleep before and after a 2 weeks rifaximine treatment in patients with hepatic encephalopathy. The primary outcome is the combined percentage of sleep spent in slow wave sleep and REM sleep, expressed as a percentage of total sleep time per 24h and assessed by 24-h polysomnography. Its timeframe is 28 days. Sleep Efficiency is named as a secondary outcome; five outcome measures and one analysis are listed.

The registry record does not report numerical primary or secondary outcome results, statistical analysis details, or missing-data methods. Serious adverse events, other adverse events, and deaths are each listed as 0 in the rifaximine group, with 15 participants at risk for each adverse-event category. The record describes the study question and design, but does not provide outcome estimates from which to judge sleep changes.