Blood Lipopolysaccharide (LPS) Rifaximin Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Blood Lipopolysaccharide (LPS) Rifaximin Study (NCT02124512), a randomized phase 2 study. The primary outcome is Circulating LPS.

2. Clinical Question

3. Trial Design

The registry describes a phase 2, randomized, double-masked, parallel-group study. The listed interventions were Rifaximin SSD and placebo. The intervention description specifies 80 mg per day of Rifaximin SSD; the treatment period in the primary endpoint description was 12 weeks. The registry enrollment is 12. The safety record lists 6 participants at risk in each arm, but those safety denominators do not establish the analysis population for the primary endpoint.

The study’s stated context is metabolic syndrome, obesity and insulin resistance. Its brief summary describes impaired insulin sensitivity and inflammation in fat tissue and the bloodstream, and presents intestinal bacteria as a possible source of inflammatory bacterial products. The planned comparison therefore linked an antibiotic intervention to circulating LPS measurements before and after treatment. This rationale explains the biological question; it does not establish that a particular treatment effect occurred.

The primary endpoint description specifies fasting and post-meal plasma LPS measurements at 0, 4 and 8 hours at baseline, with the measurements repeated after treatment. The record describes the outcome as a mean of a continuous measure and identifies standard error as the dispersion measure. It also describes the assay as a modified LAL assay. These details identify the outcome and its measurement schedule, but do not provide observed values, an effect estimate or an inferential result.

The trial is marked completed. Its recorded start is 2015-03 and its primary completion date is 2019-05-31. The sponsor is listed as Philip Kern. More detailed information about eligibility, allocation procedures, adherence, follow-up, protocol deviations and the analysis population is not reported in the registry 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.

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 Circulating LPS, measured over 0, 4 and 8 hours at Baseline, and 0, 4 and 8 hours after 12 weeks of treatment.

The primary endpoint was circulating lipopolysaccharide (LPS) in plasma, reported as a mean with standard error and measured in EU/mL. The endpoint description calls for measurement in the fasting state and after a lipid-rich meal. It specifies samples at 0, 4 and 8 hours at baseline and at 0, 4 and 8 hours after 12 weeks of treatment. LPS was measured using a modified LAL assay.

The clinical rationale is that LPS is a bacterial product that may be associated with inflammatory processes. The registry summary describes a hypothesis that intestinal bacterial products can attach to blood fats after a fatty meal and be directed to fat tissue. Measuring LPS during fasting and after a lipid-rich meal was intended to examine circulating levels in both settings, while repeating the measurements after treatment provided a way to examine whether the observed pattern differed after the treatment period.

In general, a continuous endpoint can retain information about the level of a measurement rather than reducing it to categories. Repeated measurements can describe a time pattern, but interpretation depends on the prespecified comparison and the analysis used to account for measurements collected from the same participant. Those analysis details, along with the observed LPS values and the primary treatment-effect estimate, are not reported in the registry record. The measurement schedule alone does not show whether LPS changed or whether any change differed between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as randomized, double-masked and parallel-group. In general, random allocation is intended to make treatment groups comparable with respect to both measured and unmeasured characteristics, on average. Masking is intended to limit the influence of knowledge about assigned treatment on care, measurement or assessment. These are general purposes of the design; the registry record does not report the randomization procedure, who was masked, how masking was maintained or whether it was successful.

A parallel-group design assigns participants to a group and compares outcomes between groups over the study period. It differs from a design in which each participant receives each intervention in sequence. Here, the listed groups were Rifaximin SSD and placebo. The record does not provide further operational details about allocation, treatment adherence or handling of participants who did not complete the planned treatment.

What does a mean and standard error describe?

The primary endpoint is a continuous measurement, and the record identifies the reported summary as a mean with standard error. In general, a mean describes the average measurement in a group. The standard error describes the precision of an estimated mean; it is not the same quantity as the spread of individual measurements. Standard errors can help quantify uncertainty in an estimate, but interpretation of a treatment comparison also requires the estimate being compared and its uncertainty. Those outcome summaries are not reported in the registry record.

The endpoint is expressed in EU/mL and uses a modified LAL assay. The registry describes measurements in the fasting state and after a lipid-rich meal, with measurements at 0, 4 and 8 hours at baseline and repeated at 0, 4 and 8 hours after 12 weeks of treatment. This makes the endpoint a repeated-measurement setting. In general, measurements from the same participant may be correlated; treating them as independent can misrepresent uncertainty. An analysis should account for the structure of the repeated measurements, but the specific model and covariance assumptions are not reported in the registry record.

Why does the time pattern matter?

A treatment contrast at one scheduled time point is not interchangeable with a contrast in the full time course. A summary across time points, a change from baseline, or a treatment-by-time comparison would each answer a different statistical question. The record does not identify which of these was used for the primary analysis. It notes that the primary outcome has several categories or time points and is not reduced to one comparison. No primary result or time-specific estimates are reported, so the relative pattern cannot be reconstructed from the registry record.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model assumes. It is particularly relevant when data are counts or proportions modeled with restrictive variance assumptions. The primary endpoint is described as a continuous mean, not a count outcome; no over-dispersion assessment is reported. More broadly, any model must represent the variability and dependence appropriate to its outcome. The registry does not report enough analysis detail to evaluate those choices.

What can a planning illustration tell readers?

The sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the arms and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such illustrations are hypothetical planning calculations: they describe the participants per arm associated with an assumed effect and specified statistical assumptions. They are not the trial’s observed power and do not establish that a study had a particular probability of detecting an effect after its results were known. The specific illustrated effect fractions and calculated sample-size figures are not reported in the registry record. The record also does not report the trial’s own sample-size justification or design assumptions.

In general, the precision of an estimate depends on the amount and variability of the data, and a planned sample size depends on assumptions about the effect, variability, significance level and analysis. A planning illustration based on an observed effect should not be mistaken for a prospective justification. No protocol rationale, interim analysis plan or detailed statistical analysis plan is reported in the registry record.

What does the registry record leave unresolved?

The record does not report the model used for the primary outcome, the treatment-effect contrast, the method for handling repeated measurements, the handling of missing data, or the analysis population. It also does not report whether the primary analysis was adjusted for other variables. These details matter because different reasonable analysis choices can target different quantities and yield different uncertainty estimates. Without the results and methods, no independent recalculation or assessment of the sponsor’s analysis is possible.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint includes multiple scheduled measurements: fasting and post-meal LPS at 0, 4 and 8 hours at baseline, with the schedule repeated after 12 weeks of treatment. Multiple time points create more than one potential comparison. In general, when several hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity strategy, a hierarchy among time points, or a single prespecified primary contrast. It also notes that the outcome has several time points and is not reduced to one comparison.

The record lists tissue inflammation as a secondary outcome, and identifies 3 outcome measures and 2 analyses. It does not explain how those measures and analyses correspond, what hypotheses they address, or whether any adjustment for multiple comparisons was planned. Their numerical results are not reported in the registry record.

Missing-data methods and analysis populations are also not reported. In general, missing measurements can affect a repeated-measurement analysis, particularly if the reason a value is missing is related to treatment or the outcome. A complete-case analysis, a model using available measurements, and an imputation approach rely on different assumptions. The record does not state whether any LPS measurements were missing or how missingness was handled. The safety denominators do not establish the endpoint analysis population.

Details about inclusion in the primary analysis, protocol deviations, and the handling of withdrawals are not reported in the registry record. Without these details, it is not possible to determine whether the analysis followed an intention-to-treat principle or another population definition.

11. 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 safety record lists 6 participants at risk in the Rifaximin SSD arm and 6 in the placebo arm. It reports 0 serious adverse events and 0 other adverse events in each arm, and 0 deaths in each arm. The record does not list any top serious adverse-event terms.

These figures describe what the registry reports for the listed safety categories and denominators. They do not provide event narratives, severity details beyond the serious-versus-other categories, timing, attribution to treatment, or information about how adverse events were collected. The registry record also does not explain whether there were any missing safety observations or how the safety analysis population was defined.

Zero reported events in these groups should be read as a description of the posted counts, not as proof that an intervention carries no risk. Safety findings depend on the participants observed, the duration and completeness of follow-up, and how events were defined and recorded. The registry record does not provide enough detail to assess those aspects or to make broader comparisons about safety.

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

This record describes a randomized, double-masked, parallel-group study of Rifaximin SSD versus placebo, with circulating LPS as the primary endpoint. It explains the biological motivation for measuring LPS while fasting and after a lipid-rich meal, and gives a schedule for measurements at baseline and after 12 weeks of treatment. These registry entries establish what the study set out to examine, not what the comparison found.

The registry record does not report numerical results for circulating LPS, treatment-effect estimates, confidence intervals or p-values. It therefore does not show the magnitude or direction of a difference between groups, how precise an estimate might be, or whether results varied across measurement times. Tissue inflammation is listed as a secondary outcome, but its results are also not reported in the registry record.

In general, a statistically significant result would not by itself establish that an effect is important in practice, while a non-significant result would not establish that there is no effect. Those distinctions depend on the estimated effect, its uncertainty and the question being asked. Here, those quantities are unavailable, so neither conclusion can be drawn from the posted record.

The study’s design features and biological rationale may help readers understand its purpose, but they do not answer whether treatment changed LPS or inflammation. The recorded enrollment is 12, and the safety denominators are 6 in each arm; the registry does not report the primary endpoint analysis population. The posted safety counts describe no reported events in the listed categories, but they do not establish absence of risk.

Interpretation is also limited by missing information about the primary analysis, repeated-measurement methods, missing data, multiplicity and the relation between the outcome measures and analyses. The appropriate conclusion is therefore narrow: the registry describes a completed study and its intended comparison, but does not report the outcome findings needed to assess the treatment effect.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its primary endpoint was measured repeatedly, both before and after treatment, and in fasting and post-meal conditions. Such a design raises an important distinction between asking whether groups differ at a selected measurement time and asking whether the pattern over time differs between groups. Those are not interchangeable estimands. The registry record does not report which contrast was used or provide results that would let readers assess the pattern.

The study also illustrates why an endpoint’s biological rationale and its statistical interpretation should be kept separate. The registry describes a possible link between gut bacteria, circulating LPS and inflammation. The measurements were intended to examine that rationale, but only reported outcome data and a suitable analysis could show whether the study observed a difference. The endpoint values and analysis results are not reported in the registry record.

Repeated observations also require attention to within-participant dependence. In general, measurements from the same person are often related, and an analysis should reflect that structure when estimating uncertainty. The methods needed to judge this issue are not reported. The record’s description of a continuous mean with standard error identifies a summary format, but it does not specify the model or treatment contrast.

Finally, the planning assumptions illustrate a general point: sample-size calculations depend on a chosen effect and statistical assumptions. A calculation based on an observed effect is a planning illustration, not evidence that the study was adequately powered in advance and not observed power. The registry record does not report its own sample-size justification. This combination of a biologically motivated, repeated-measurement endpoint and missing outcome and analysis details makes careful separation of design, planning and evidence especially important.

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 main limitation for interpreting this study is that numerical primary endpoint results are not reported in the registry record. Without group summaries, treatment contrasts and uncertainty estimates, the LPS findings cannot be evaluated. The record’s outcome description gives the measurement schedule and assay, but not the observed values.

The endpoint is measured at multiple time points and in fasting and post-meal conditions. The record does not identify a single primary contrast, explain how measurements were modeled, or report how within-participant dependence was handled. It also does not report a plan for multiplicity across time points or outcomes. These omissions make it difficult to determine what inferential question the reported analysis would answer.

Details about missing LPS measurements, withdrawals, adherence, protocol deviations and the primary analysis population are not reported in the registry record. The listed safety denominators cannot resolve these questions about the endpoint population. Further eligibility criteria and the implementation of randomization and masking are also not described in the record.

The study is marked completed, but the record does not report the primary results or the findings for the listed secondary outcome of tissue inflammation. It identifies 3 outcome measures and 2 analyses without explaining their mapping or reporting their findings. The record also does not provide a sample-size justification for the trial. These limitations concern what can be assessed from the registry record; they do not establish that particular methods were or were not used outside the information recorded there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Blood Lipopolysaccharide (LPS) Rifaximin Study — NCT02124512.
• Registry record last updated 2019-08-21; status last verified 2019-08.
• Results first posted 2019-08-21.
• 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

The record describes a completed phase 2 randomized, double-masked, parallel-group study titled “Blood Lipopolysaccharide (LPS) Rifaximin Study,” with the official title “Dietary Fat, Lipoprotein and Lipopolysaccharide: Role in Insulin Resistance.” It lists obesity, insulin resistance and metabolic syndrome as conditions, and Philip Kern as sponsor. The recorded start is 2015-03 and the primary completion date is 2019-05-31.

The interventions were Rifaximin SSD, described as 80 mg per day, and placebo. The primary endpoint was circulating LPS in EU/mL, measured at 0, 4 and 8 hours at baseline and again after 12 weeks of treatment. The endpoint description refers to fasting and post-meal measurements using a modified LAL assay. Tissue inflammation is listed as a secondary outcome.

The registry enrollment is 12. Safety counts report 0 serious adverse events, 0 other adverse events and 0 deaths in each arm. Numerical primary and secondary outcome results, analysis details and the primary endpoint analysis population are not reported in the registry record.