Trial of Rifaximin in the Treatment of Tropical Enteropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of Rifaximin in the Treatment of Tropical Enteropathy (NCT00858988), a randomized na study. The primary outcome is Difference in the Urinary L:M Ratio Before and After the Intervention.

2. Clinical Question

The endpoint was based on a sugar-permeability test. Children drank a solution containing lactulose and mannitol, among other sugars, and urine was collected for 4 hours after ingestion. The registry states that the reported values for a normal L:M ratio range from 0.03 to 0.12, and that a value of at least 0.10 was chosen as indicative of tropical enteropathy. The test was performed at enrollment and again 28 days later.

The recorded result is a comparison of group mean changes, rather than a comparison of the proportions of children above or below the stated threshold. The question is therefore about the average change in this continuous urinary measure over the specified period, not about a separately reported diagnosis rate or clinical outcome.

3. Trial Design

This was a randomized, parallel-group trial comparing rifaximin with placebo. The official title describes it as double-blind and placebo-controlled, while the registry lists quadruple masking. The record does not explain the roles included in the masking designation. Allocation was randomized; details of the sequence generation and allocation concealment are not reported in the registry record.

The registry lists enrollment as 147 and the posted outcome summaries report 72 participants in each arm. The record does not explain the relationship between the enrollment figure and the arm-level numbers, or whether these numbers refer to different analysis populations or stages of the trial. The arm descriptions contain no further treatment details. Dose, administration schedule, adherence, and use of other care are not reported in the registry record.

The study is listed as completed. Its recorded start was 2007-09 and its primary completion was 2007-10. The phase field is listed as NA. Washington University School of Medicine is identified as the sponsor.

The primary outcome was the difference in urinary L:M ratio before and after intervention, with a timeframe of 28 days. The registry describes testing at enrollment and 28 days later. It reports a continuous outcome summarized as a mean with standard deviation. One outcome measure is listed, and there are no secondary outcomes reported. No analysis results are listed beyond the posted primary comparison, and no separate statistical analysis plan is reported in the registry record.

These details describe the design features recorded in the registry, but do not supply the full protocol. Eligibility criteria, the planned sample-size justification, the planned analysis population, handling of missing measurements, and any interim monitoring procedures are not reported in the registry record. Those omissions limit what can be concluded about how closely the posted summaries reflect the original design and analysis plan.

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.

Randomized and Allocation

Analysis

Reasons for not completing this period:

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 Difference in the Urinary L:M Ratio Before and After the Intervention, measured over 28 days.

The primary endpoint was the difference in urinary lactulose-to-mannitol ratio before and after the intervention. The registry describes a test in which each child drank a solution containing lactulose, mannitol, sucralose, and sucrose. Urine was collected for 4 hours after ingestion. Testing took place at enrollment and again 28 days later.

The L:M ratio is a continuous measure from the sugar test. The registry reports that normal values range from 0.03 to 0.12 and that a value of at least 0.10 was chosen to indicate tropical enteropathy. These thresholds provide context for the test, but the posted primary analysis is a comparison of mean changes in the ratio between groups. It does not report a comparison of the proportion of participants crossing the threshold.

In general, a continuous endpoint retains information across the range of measured values, rather than reducing each result to a category. Comparing change from enrollment can describe how the measure shifted over the study period in each group. The mean difference then describes the contrast between those group-level changes. The registry record does not report how individual measurements were processed, whether any transformations were used, or how values outside an expected range were handled.

The endpoint is a laboratory-based measure. The registry does not report a separate patient-centered endpoint or a link between changes in this ratio and later health outcomes. Its interpretation should therefore remain specific to the urinary L:M measure over the 28-day timeframe.

7. Results Posted in the Registry

• Rifaximin: mean -0.01 versus 0.02 on control; difference -0.03 (95% CI -0.08 to 0.02), standardized effect d = -0.21; z-test p = 0.203.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean difference represent?

The primary result is reported as a mean difference between the rifaximin and placebo groups. For a continuous outcome, a group mean describes the average measured value or average change in that group. A mean difference compares the two group averages on the same scale. Here, the posted contrast is -0.03 for rifaximin relative to placebo. Its negative sign indicates that the rifaximin group’s reported mean change was lower than the placebo group’s reported mean change.

A group mean does not imply that every participant changed by that amount. Individual results can vary around the mean, as indicated by the reported standard deviations. Nor does a mean difference describe the number of participants whose results moved in a particular direction. Such questions would require individual-level or categorical summaries, which are not reported for this endpoint.

What do the standard deviations describe?

The posted standard deviations are 0.12 for rifaximin and 0.16 for placebo. In general, a standard deviation describes how dispersed measurements are around their mean. A larger standard deviation indicates greater spread in the observed values, but it is not itself a measure of uncertainty in the mean difference. Precision of a group comparison depends on the variability and the amount of information available for the comparison.

The registry does not report distribution plots or participant-level data. It is therefore not possible to assess the shape of the measurement distributions, identify outliers, or determine whether the standard deviations adequately summarize any skewness. These are possible considerations for continuous outcomes in general, not findings established by the posted summaries.

How should the confidence interval be understood?

In general, a confidence interval describes the range of effect estimates that are reasonably compatible with the data under the method and assumptions used to construct it. A narrower interval indicates greater precision; a wider interval indicates greater uncertainty. The registry’s reported interval for the mean difference spans negative and positive values and includes zero. That means the posted result does not rule out no between-group difference, while also allowing for values in either direction.

A confidence interval is not a range containing every participant’s result, and it is not a guarantee that the true effect lies inside the particular interval. Its interpretation depends on the confidence level and the statistical procedure. The confidence level and full interval method are not reported in the registry record, so those details should not be inferred.

What does the p-value add?

The unadjusted p-value is 0.203. In general, a p-value evaluates how compatible the data are with a specified null hypothesis, subject to the model and assumptions used for the test. A larger p-value does not establish that there is no effect, and a smaller p-value would not by itself describe the size or practical importance of an effect. The p-value is not the probability that a treatment works or that the null hypothesis is true.

The registry labels this p-value unadjusted. The record does not describe a multiplicity adjustment, the exact test used, or the complete statistical model. It is therefore best treated as the reported unadjusted significance measure, rather than as evidence about an unreported adjusted analysis.

Why can over-dispersion matter?

In general, over-dispersion refers to greater variability in data than a model assumes. If a model underestimates variability, its standard errors and intervals can be too small, making results appear more precise than warranted. This concept is often important for count outcomes and some other data structures. The primary endpoint is continuous, and the registry does not report a model that identifies or tests over-dispersion. It should not be claimed that over-dispersion was present or that a particular correction was used.

What analysis details remain unknown?

The registry identifies the endpoint as a mean and its dispersion as a standard deviation, and gives arm-level summaries and a mean difference. It does not report the exact analysis model, the test procedure, adjustment variables, assumptions about missing values, or whether the analysis followed intention-to-treat or another population definition. Those details matter because they explain how the reported estimate and uncertainty were obtained and which participants contributed to them.

The registry reports 147 enrolled and an outcome summary of 72 in each arm, but does not explain the relationship between those counts. The number of analyses is listed as zero, although a primary comparison is posted. The record does not clarify what the analysis-count field represents. No reconciliation should be assumed. The statistical interpretation should remain tied to the posted summary statistics and the limited analysis detail recorded.

10. Confidence Intervals and Precision

The reported mean difference is -0.03, and its reported interval extends from a negative value to a positive value, including zero. This interval conveys uncertainty around the group contrast. Because it includes zero, the posted data do not exclude no difference between the groups. The range also permits a difference in either direction, so the point estimate alone should not be treated as a precise description of the underlying contrast.

Precision is distinct from the direction of the estimate. The estimate is negative for rifaximin relative to placebo, but the interval indicates that uncertainty remains about the direction and size of the contrast. Without the confidence level and method for constructing the interval, details of its statistical calibration are not reported in the registry record.

The arm standard deviations are 0.12 and 0.16, which show that measurements varied within each group. In general, the precision of a mean difference depends on both variability and the amount of information contributing to the estimate. The record gives arm-level outcome counts of 72 for each group, but it does not report whether those counts represent all randomized participants or how missing measurements were handled. This limits assessment of how much information supports the endpoint comparison.

The unadjusted p-value of 0.203 is consistent with uncertainty about a between-group difference under the test used. It should not be converted into a claim of equivalence or a claim that an effect is absent. The registry does not report a prespecified margin for an equivalence or non-inferiority assessment. The result is most appropriately read as an estimate with uncertainty, rather than as a definitive classification of the treatments as different or the same.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total event counts. They are illustrations based on the observed effect, rather than the original trial’s design calculations. The original sample-size assumptions and justification are not reported in the registry record. This is not observed power.

The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. At 100% of the observed effect, the illustration gives 349 participants per arm for 80% power and 467 participants per arm for 90% power. At 75% of the observed effect, the figures are 621 participants per arm for 80% power and 831 participants per arm for 90% power. At 50% of the observed effect, the figures are 1,396 participants per arm for 80% power and 1,868 participants per arm for 90% power.

In general, power is the chance that a study will detect an effect of a specified size under a particular set of assumptions, if that effect is present. The 80% and 90% columns describe different planning targets: the 90% target aims for a higher chance of detecting the specified effect than the 80% target, and therefore requires more participants under these assumptions. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants per arm.

These illustrations use the observed effect as their reference and should not be read as evidence about the probability that the completed trial detected an effect. They do not recover the original planning rationale, and they do not account for any design or analysis choices that are not reported in the registry record.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.030; pooled standard deviation σ = 0.141.
2. n = 2 × (1.96 + 0.842)² × 0.141² / -0.030² = 348.8, rounded up to 349 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.03                      # observed difference in means
sigma <- 0.14142135623731                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(858988)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 349 (80% power), 467 (90% power)
 75% of observed effect: n per arm = 621 (80% power), 831 (90% power)
 50% of observed effect: n per arm = 1,396 (80% power), 1,868 (90% power)
power.t.test: 349.8 
Simulated power at n = 349 per arm: 0.807 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, subgroups, or repeated analyses are tested. In general, conducting many tests can increase the chance that at least one result appears statistically notable even when there is no corresponding effect. A prespecified primary outcome and a defined analysis plan help readers understand which comparison was central and whether adjustments are appropriate.

The registry lists one outcome measure and no secondary outcomes. The posted primary comparison has an unadjusted p-value of 0.203. The record does not report whether other outcomes or analyses were planned but not posted, whether there were subgroup comparisons, or whether any multiplicity strategy was prespecified. No adjustment should be assumed, and the absence of secondary outcomes in the record does not establish what may or may not have been examined outside the posted results.

The registry does not report a statistical analysis plan, the exact analysis model, or a definition of the analysis population. It therefore does not establish whether the primary analysis was intention-to-treat, per-protocol, or based on another population. The record also does not explain how deviations from assigned treatment, adherence, or other protocol events were handled.

Missing data handling is not reported. The arm summaries list 72 participants in each group, while registry enrollment is 147. The reason for the difference is not stated, and it cannot be determined from the record whether it reflects endpoint availability, a difference in reporting stages, or another explanation. The number of participants with missing measurements, the reasons for missingness, and any imputation or sensitivity analyses are not reported in the registry record.

In general, missing outcome data can affect both the estimate and its precision, particularly when the reasons for missingness are related to outcome values or treatment assignment. Without the missing-data procedures and analysis-population details, readers cannot assess those possibilities for this trial. The posted comparison remains interpretable as the registry’s reported result, but its relationship to all randomized participants is unclear.

14. 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 for the rifaximin group and zero for the placebo group. It also reports zero other adverse events in both groups, and zero deaths in each group. The safety summaries list 72 participants at risk in each arm for serious and other adverse events.

These counts describe the events recorded in the registry, not the probability of every possible harm. The record does not report definitions of serious or other adverse events, the observation period used for safety reporting, how events were collected, or whether events were considered related to treatment. It also does not provide detailed event terms; no serious-event terms are listed.

Zero recorded events should not be read as proof that no adverse events occurred outside the registry’s reporting or ascertainment process. Nor do these counts support a broad comparison of safety across settings or over longer periods. They are limited to the posted safety figures and their reported at-risk groups.

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

The result describes a comparison of mean changes in urinary L:M ratio between children assigned to rifaximin and those assigned to placebo over the trial’s 28-day timeframe. The posted means are -0.01 for rifaximin and 0.02 for placebo, with a reported mean difference of -0.03. The interval for that difference includes zero, and the unadjusted p-value is 0.203. Together, these findings indicate uncertainty about the size and direction of the group contrast.

The result does not show that the groups were equivalent. Demonstrating equivalence requires a prespecified margin and an analysis designed to assess whether the plausible difference lies within that margin; such a margin or analysis is not reported in the registry record. A non-significant result, or an interval that includes zero, is not by itself proof that there is no effect.

The result also does not establish that rifaximin works or does not work. It is limited to the registry’s primary continuous outcome and the reported 28-day period. The record does not post secondary outcomes, an analysis of the proportion meeting the L:M threshold, or longer-term follow-up results. It therefore cannot answer broader questions about clinical outcomes or durability.

The endpoint is a urinary sugar-test measure, and its reported normal range and chosen threshold provide context for interpreting individual values. However, the primary result is a difference in group mean changes, not a count of participants who reached a particular value. The group means cannot establish how many individuals crossed the threshold or how their clinical status changed.

Finally, uncertainty about the analysis population and missing data remains. The registry lists enrollment as 147 and reports outcome counts of 72 per arm, without reconciling them. The posted data should be interpreted within those reporting limits and should not be extended beyond the endpoint, population, and follow-up described in the record.

16. Why This Trial Matters Statistically

This trial illustrates several central issues in interpreting randomized clinical research. Random allocation and a placebo comparator provide a framework for comparing groups, but the meaning of the estimate still depends on the outcome definition, analysis population, missing-data handling, and precision. The registry identifies a continuous primary endpoint and reports a mean difference, standard deviations, an interval, and an unadjusted p-value. Those measures answer related but distinct questions.

The mean difference gives the estimated direction and size of the group contrast on the outcome scale. The interval communicates uncertainty around that estimate, while the p-value assesses compatibility with a specified null hypothesis under the test assumptions. In this trial, the interval includes zero and the unadjusted p-value is 0.203. Neither statistic should be interpreted alone as proof of no difference, equivalence, or treatment benefit.

The endpoint also highlights the distinction between a continuous measure and a threshold. The registry gives a chosen L:M threshold for indicating tropical enteropathy, but the posted primary result compares mean changes rather than threshold-based outcomes. A mean contrast does not reveal how many participants exceeded the threshold or whether individuals experienced changes of clinical importance.

Reporting details matter as well. The enrollment figure and arm-level outcome counts are not reconciled, while the analysis population and missing-data procedures are not reported. These omissions do not invalidate the posted summary, but they constrain judgments about who contributed to it and how complete the endpoint data were. Clear reporting of these elements would help readers connect the randomized design to the analyzed outcome.

17. 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 registry record gives limited detail about the trial procedures. It does not report the rifaximin dose, dosing schedule, duration of administration, eligibility criteria, allocation sequence method, or allocation concealment. Although the trial is described as quadruple-masked and double-blind in its title, the roles covered by masking are not specified.

The primary endpoint is described as a difference in urinary L:M ratio before and after intervention, with testing at enrollment and 28 days later. The record does not detail the calculation of the change score, the handling of unusual measurements, or the exact statistical test. It also does not report whether adjustment was made for baseline measurements or other covariates.

The registry lists 147 enrolled, while the arm-level outcome summaries report 72 in each group. The relationship between these figures is not explained. The record does not report the analysis population, participant flow, missing measurements, reasons for missingness, or procedures used to address missing data. This prevents a clear assessment of whether the reported endpoint summaries include all randomized participants.

Only one outcome measure is listed and no secondary outcomes are posted. The record does not establish whether there were additional planned outcomes or analyses, and does not report a multiplicity plan. The original sample-size rationale and design assumptions are also not reported; the separate planning illustrations are based on the observed effect and do not establish what the original investigators planned.

The posted safety figures contain no recorded serious or other adverse events and no deaths, but safety definitions, ascertainment methods, and follow-up duration for these summaries are not reported. These limitations concern the available registry information and should not be taken as evidence that unreported procedures or outcomes were absent.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Trial of Rifaximin in the Treatment of Tropical Enteropathy — NCT00858988.
• Registry record last updated 2019-11-12; status last verified 2019-11.
• Results first posted 2019-11-12.
• 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.

21. Record Summary

The registry record describes a completed randomized, parallel-group, placebo-controlled trial of rifaximin in African children at high risk for tropical enteropathy. It lists double-blind and quadruple masking. Washington University School of Medicine is the sponsor; the recorded start was 2007-09 and primary completion was 2007-10. The phase is listed as NA.

The primary endpoint was the difference in urinary L:M ratio before and after intervention, measured over 28 days. The reported mean difference was -0.03, with an interval that includes zero and an unadjusted p-value of 0.203. The registry reports zero serious adverse events, zero other adverse events, and zero deaths in each arm.

Enrollment is listed as 147, while the primary outcome summaries report 72 participants per arm. The record does not explain the difference or report the analysis population, missing-data procedures, or original sample-size rationale. No secondary outcomes are posted.