Study to Assess Inhibition of Spore Production in Patients With C. Difficile Infections: Fidaxomicin Versus Vancomycin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Inhibition of Spore Production in Patients With C. Difficile Infections: Fidaxomicin Versus Vancomycin (NCT01818141), a randomized phase 4 study. The primary outcome is C. Difficile Spore Reduction of at Least 2 Log 10 Colony Forming Units (CFU)/g of Stool.

2. Clinical Question

The trial asked whether patients with a first episode of C. difficile infection who received fidaxomicin or vancomycin differed in their reduction of stool spores by the end of therapy. The primary endpoint focused on whether a participant achieved a reduction of at least 2 log10 colony forming units (CFU)/g of stool from baseline during days 10-13.

The endpoint is a threshold-based outcome: it classifies participants according to whether they crossed the stated reduction threshold. The registry record lists 11 participants in the fidaxomicin group and 6 in the vancomycin group as achieving the endpoint. These counts are descriptive. The record does not post an inferential comparison, such as a confidence interval or p-value, so the counts alone do not establish the precision of a between-group difference.

The question is about spore reduction over the specified period, not a broader assessment of all clinical outcomes. Although the brief summary mentions vegetative cells and spores over time, the posted primary endpoint is the proportion meeting the specified spore-reduction threshold. The registry record does not report a primary analysis of vegetative-cell counts.

3. Trial Design

This was a Phase 4, randomized, open-label, parallel-group study sponsored by Hartford Hospital. The registry record lists enrollment of 34 participants. The study is marked completed, with a start date of 2012-10-17 and a primary completion date of 2014-12-15. These record details describe the trial’s structure and status; they do not themselves establish how participants were recruited, followed, or included in the endpoint analysis.

Participants were assigned to fidaxomicin or vancomycin. In the fidaxomicin arm, the listed regimen was 200mg by mouth every 12 hours for 10 days. In the vancomycin arm, the listed regimen was 125mg by mouth every 6 hours for 10 days. The parallel design means the registry describes separate groups receiving the two interventions. Masking is listed as none, so the study was open-label.

The primary endpoint concerns a reduction of at least 2 log10 CFU/g of stool from baseline, assessed by the end of therapy during days 10-13. The endpoint results list 12 participants in the fidaxomicin group and 9 in the vancomycin group. The registry record does not explain how these endpoint denominators relate to the enrollment figure, or why they differ from the safety denominators. It also does not report whether the endpoint analysis followed an intention-to-treat, per-protocol, or other population definition.

Randomization is relevant because, in general, it aims to make treatment groups comparable with respect to factors that could affect an outcome. It does not remove uncertainty, guarantee balance in a small study, or address the potential effects of an open-label design. The registry record does not report the randomization method, allocation concealment procedures, or a protocol-level explanation of how those procedures were conducted.

The posted primary result is a count in each group, but no formal comparative analysis is listed. The registry record does not report the planned analysis method, any interim analyses, or a sample-size justification. These omissions limit what can be concluded about the design’s statistical aims and the interpretation intended by the study investigators.

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

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 C. Difficile Spore Reduction of at Least 2 Log 10 Colony Forming Units (CFU)/g of Stool, measured over day 10-13.

The primary endpoint is the number and percentage of patients who achieved at least a 2 log10 CFU/g reduction in C. difficile spores in stool from baseline by the end of therapy, during days 10-13. It is recorded as a participant-level count: each participant either meets the threshold or does not, based on the endpoint definition. The posted results list 11 participants meeting the threshold in the fidaxomicin group and 6 in the vancomycin group.

A threshold endpoint turns a measured change into a binary classification. In general, this can make a result easier to describe as the number of participants meeting a defined target. It also means that the classification does not show how far above or below the threshold each person’s result fell. Participants with different measured reductions can be grouped together if they fall on the same side of the threshold.

The endpoint is used to assess whether participants reached a specified degree of spore reduction over the stated period. The registry record does not explain why this particular threshold was selected, how stool samples were collected or processed, or how measurements were handled if a sample was unavailable. Those details are not reported in the registry record.

The brief summary describes comparing vegetative cells and spores in stool over time, but the posted primary outcome is specifically the binary spore-reduction measure. It should not be treated as a complete account of every biological measurement or clinical outcome. The registry record lists 2 outcome measures, but it does not post secondary results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives a randomized, open-label, parallel-group design and a binary primary outcome. It does not report the statistical methods used for the primary comparison. The explanations below describe general statistical concepts that help frame the posted results; they should not be taken as a description of an analysis plan that is absent from the registry record.

What does a binary endpoint represent?

A binary endpoint classifies each participant into one of two categories. Here, the categories correspond to whether a participant achieved the defined spore reduction threshold by the specified end-of-therapy period. The posted results give the number meeting the threshold and the number of participants listed in each group. A binary outcome can be summarized with counts and proportions, but the registry record does not post the proportions or a formal comparison.

In general, a comparison of two binary outcomes might report a difference in proportions, a ratio of proportions, or an odds ratio. Each measure answers a different question and can present the magnitude of a group contrast in a different way. The registry record does not identify which, if any, of these measures was planned or used. No adjusted or unadjusted treatment-effect estimate is posted.

Why does a confidence interval matter?

In general, a confidence interval communicates uncertainty around an estimated effect. A narrow interval indicates greater precision under the model used, while a wide interval indicates less precision. Interpretation depends on the interval’s construction, the endpoint, and the analysis population. Because no interval is reported for the primary endpoint, the precision of the comparative result cannot be assessed from the registry record.

In general, a p-value is not a measure of the size or clinical importance of an effect. It is interpreted in relation to a statistical model and a null hypothesis. A p-value alone also does not show the precision of an estimate. The registry record does not report a p-value, a null hypothesis, or a testing procedure for the primary comparison.

What can randomization contribute?

In general, random assignment is intended to reduce systematic differences between groups at the time of allocation. It does not ensure that every characteristic will be balanced, particularly when the groups are small, and it cannot correct problems arising after assignment, such as missing outcome measurements or differences in follow-up. The record confirms randomization but does not describe the random sequence, allocation concealment, or any stratification factors.

Because the study was open-label, participants and study staff were not masked according to the registry. In general, this may influence treatment behavior, co-interventions, reporting, or outcome assessment. The extent of any such influence depends on the study procedures and endpoint measurement. The registry record does not report whether laboratory staff were masked to treatment assignment or give other details that would clarify this issue.

How should the endpoint counts be read?

The primary result lists 11 participants meeting the threshold among 12 in the fidaxomicin group and 6 among 9 in the vancomycin group. These are observed counts in the posted endpoint result. They are not, by themselves, an estimate of uncertainty or a test of a treatment difference. The group sizes listed for this outcome differ from the enrollment figure, and the registry record does not explain participant flow into the endpoint analysis.

A valid analysis depends on knowing which participants were included, how missing measurements were handled, and what estimand or comparison was intended. In general, an intention-to-treat analysis keeps participants in their randomized groups, while other analysis populations may impose additional conditions. The registry record does not identify the analysis population or say whether the listed outcome counts include all randomized participants with available data, a selected subset, or another defined group.

What does the sample-size information describe?

The sample-size assumptions described for planning illustrations refer to two-sided significance level 0.05, equal allocation between groups, a normal approximation, and an effect defined as a stated fraction of the observed effect. The assumptions also distinguish participant-per-arm illustrations from total-event illustrations for time-to-event outcomes. These are planning assumptions, not a description of the trial’s original design calculation. The registry record does not report the trial’s own sample-size justification.

Planning illustrations based on an observed effect should not be interpreted as observed power. In general, such illustrations show how a hypothetical future study might be sized under specified assumptions; they do not establish that the current study had adequate power or that the observed effect is reliable. No numerical sample-size illustration results are stated in the registry record, and the primary comparison is not estimable in the posted two-arm analysis. The sponsor’s own analysis takes precedence when a discrepancy is recorded; the registry record does not flag a discrepancy.

What is not described?

The registry record does not report the planned statistical model, adjustment variables, missing-data method, treatment of repeated measurements, or handling of protocol deviations for the primary outcome. It does not report interim analyses or a multiplicity procedure. Without those details and without a posted comparative estimate, a reader cannot reconstruct or independently evaluate the intended inferential analysis from the registry record alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Fidaxomicin", "Vancomycin")
n      <- c(12, 9)
events <- c(11, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Fidaxomicin  12  11  91.7  61.5  99.8  64.6  98.5  64.0  98.1
ARM  Vancomycin  9  6  66.7  29.9  92.5  35.4  87.9  34.8  87.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures and 0 posted secondary outcomes. The primary result is the threshold-based spore-reduction endpoint during days 10-13. Although the brief summary mentions comparing vegetative cells and spores over time, the registry record does not post secondary outcome results for those measurements.

Multiplicity refers, in general, to the statistical issue that can arise when several hypotheses or outcomes are tested. The chance of obtaining at least one apparently notable result can change when many tests are conducted. A study may address this through a prespecified hierarchy, adjustment, or another strategy. The registry record does not report whether any multiplicity plan was used, and no interim analyses are reported.

The record lists endpoint group sizes of 12 for fidaxomicin and 9 for vancomycin, while enrollment is listed as 34. It does not explain the relationship between enrollment and the primary endpoint analysis, identify reasons participants may not appear in the endpoint counts, or state whether all randomized participants were analyzed. The safety fields use their own denominators, which are listed separately.

Missing-data handling is not reported in the registry record. In general, missing outcome measurements can affect both the analysis population and the interpretation of a group comparison. Different assumptions or methods for handling missing values can produce different estimates. The record does not state whether missing measurements occurred, whether any imputation was performed, or whether sensitivity analyses were conducted.

The registry record also does not define the primary analysis population or identify a prespecified statistical analysis plan. It is therefore not possible to determine from the posted information whether the reported endpoint counts reflect an intention-to-treat population, a per-protocol population, or another set of participants.

12. Safety Results

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

Other (non-serious) adverse events

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

The safety fields list 0 serious adverse events among 18 participants at risk in the fidaxomicin group, and 0 serious adverse events among 16 participants at risk in the vancomycin group. The registry also lists 0 other adverse events among 18 and 16 participants at risk, respectively. These are the figures entered in the posted safety results.

These entries should be read with their denominators and record limitations in view. The safety groups have their own at-risk counts; they should not be assumed to be the same populations as those listed for the primary endpoint. The registry record does not explain the relationship between those groups, or provide a detailed safety analysis population.

The deaths fields are not reported in the registry record. The record does not provide further details about adverse-event definitions, collection methods, follow-up duration, seriousness criteria, or how events were attributed. It also does not describe whether the listed zeros represent complete ascertainment for every participant. Thus, the figures describe the posted safety entries, rather than offering a full account of the trial’s safety monitoring or all possible adverse events.

In general, an event count of zero in a posted field does not by itself establish the absence of risk. Interpretation depends on how events were sought, the length and completeness of follow-up, and the number of participants observed. Those details are not reported in the registry record.

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

The posted results show the number of participants recorded as achieving the primary stool-spore reduction threshold: 11 in the fidaxomicin group and 6 in the vancomycin group. The endpoint group sizes are listed as 12 and 9. This is a descriptive summary of the registry’s binary outcome, tied to baseline and the end-of-therapy period of days 10-13.

The result does not, on its own, establish the size or precision of a between-group effect. No comparative estimate, confidence interval, or p-value is reported in the registry record, and a two-arm comparison is not estimable in the posted analysis. The counts should not be treated as proof of a difference or of no difference. They also do not provide the underlying stool measurements or show how much each participant’s spore level changed.

The endpoint is narrower than the full clinical question a reader might have about treatment. It assesses a stated degree of spore reduction over a particular period; it does not directly report all symptoms, recurrence, other clinical outcomes, or the full trajectory of vegetative cells and spores. The brief summary mentions vegetative cells and spores over time, but the posted primary result is the threshold-based spore endpoint.

The registry describes a randomized, open-label study, but it does not report the analysis population, missing-data handling, or detailed endpoint assessment procedures. It lists enrollment of 34 participants, while the primary endpoint result lists groups of 12 and 9. The reasons for this difference are not reported in the registry record. This limits assessment of how representative the posted counts are of the enrolled study population.

The safety entries list 0 serious adverse events and 0 other adverse events in each group, with at-risk counts of 18 and 16. Deaths are not reported in the registry record. These safety entries are not a substitute for a complete safety analysis, particularly because event ascertainment and follow-up details are not reported.

Accordingly, the posted information supports a factual description of endpoint and safety counts, but not a firm statistical conclusion about comparative effects. Any interpretation should remain confined to the recorded endpoint, its stated time window, and the limited analysis information available in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because a clearly worded endpoint and a randomized design do not by themselves provide a complete basis for interpreting a treatment comparison. The registry identifies a threshold-based primary endpoint, gives group counts, and records that allocation was randomized. Yet it does not post a comparative estimate or its uncertainty. Readers can see the recorded counts but cannot assess the precision of a treatment contrast from those counts alone.

The record also illustrates why denominators and analysis populations matter. Enrollment is listed as 34, while the primary endpoint groups are listed as 12 and 9. The safety groups have separate at-risk counts. Without an account of participant flow and analysis-set definitions, a reader cannot determine why these denominators differ or how missing endpoint measurements were handled.

Another statistical issue is the distinction between a biological measurement and a threshold-based endpoint. The primary outcome classifies participants according to whether they reached a specified reduction. In general, dichotomizing a measured change can make results straightforward to summarize, but it can conceal differences in the magnitude of change among participants within each category. Here, the registry does not report the underlying distributions needed to examine that information.

The open-label design also makes the description of outcome assessment relevant. The record does not say whether laboratory assessment was masked or provide details about sample collection and processing. Such information can help readers assess how the design may influence measurement, even when an endpoint is based on a laboratory result.

Finally, the registry lists no secondary results and no inferential analysis for the primary comparison. This makes the distinction between planned methods, posted data, and statistical interpretation especially important. Descriptive counts are useful, but without a reported analysis plan and uncertainty estimate, they do not answer every question a reader may have about the strength or precision of the comparison.

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 registry record does not report the statistical analysis plan, the planned test or model, a treatment-effect estimate, a confidence interval, or a p-value for the primary endpoint. It also does not report the trial’s sample-size justification, interim analyses, or a multiplicity strategy. These omissions prevent a detailed assessment of the intended inferential approach.

The primary endpoint counts are listed for groups of 12 and 9, while enrollment is listed as 34. The record does not explain participant flow, reasons for missing endpoint data, or how participants were selected for the posted result. It does not identify an intention-to-treat or other analysis population. The safety denominators are listed separately, and the relationship between them and the endpoint groups is not explained.

The study is open-label, and the registry record does not describe masking of laboratory staff or the procedures used to collect and assess stool samples. It does not report the measurement schedule beyond the primary endpoint’s stated days 10-13 period, or explain how unavailable or outlying measurements were handled.

The brief summary refers to vegetative cells and spores over time, but the registry lists 0 posted secondary outcomes. Thus, readers do not have secondary result details in the registry record with which to assess the broader measurement program. The record also does not explain the rationale for the endpoint threshold or provide the underlying quantitative stool measurements.

For safety, the registry lists 0 serious and 0 other adverse events in each group, but it does not report deaths, event-collection procedures, follow-up details, or further event definitions. These limitations mean that the safety fields should be read as a limited record of reported counts, not as a comprehensive account of safety evidence.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess Inhibition of Spore Production in Patients With C. Difficile Infections: Fidaxomicin Versus Vancomycin — NCT01818141.
• Registry record last updated 2017-06-28; status last verified 2017-05.
• Results first posted 2017-06-28.
• 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

This completed Phase 4 study was randomized, open-label, and parallel-group, with enrollment listed as 34. It compared fidaxomicin 200mg by mouth every 12 hours for 10 days with vancomycin 125mg by mouth every 6 hours for 10 days in patients diagnosed with their first episode of C. difficile infection.

The primary endpoint was achievement of at least a 2 log10 CFU/g reduction in stool spores from baseline by the end of therapy, during days 10-13. The posted result lists 11 participants meeting the threshold in the fidaxomicin group and 6 in the vancomycin group, with endpoint group sizes of 12 and 9. No comparative estimate or inferential analysis is reported.

The safety fields list 0 serious and 0 other adverse events in groups with 18 and 16 participants at risk. Deaths, analysis populations, missing-data handling, and the trial’s statistical plan are not reported in the registry record.