This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Optimal Treatment for Recurrent Clostridium Difficile (NCT02667418), a randomized phase 4 study. The primary outcome is Number of Participants With Sustained Clinical Response as Measured at Study Day 59 for All Treatment Regimens.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02667418 |
| Phase | Phase 4 |
| Condition | Clostridium, Difficile, Fidaxomicin |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 308 |
| Arms in the primary outcome | n/a |
| Lead sponsor | VA Office of Research and Development |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with recurrent Clostridium difficile infection. The registry record describes a modified intention-to-treat population for the primary analysis, but the full eligibility criteria and the exact definition of that analysis population are not reported in the registry record. Enrollment was 308.
Intervention
One group received standard 10-day fidaxomicin treatment. A second group received standard 10-day vancomycin followed by taper and pulse vancomycin treatment. The descriptions identify treatment regimens but do not report further dosing details in the registry record.
Comparator
The comparator was standard 10-day vancomycin treatment. The study was randomized, double masked, and used a parallel design. The registry describes three treatment groups; details of how masking was implemented are not reported in the registry record.
Primary question
The study aimed to determine whether fidaxomicin and vancomycin followed by taper and pulse treatment were superior to standard vancomycin for recurrent infection. The primary outcome was sustained clinical response measured at study day 59. The registry record does not report the outcome counts or a statistical comparison, so it does not establish the direction or precision of any treatment-group differences.
3. Trial Design
This was a phase 4, randomized, double-masked, parallel-group study sponsored by the VA Office of Research and Development. The registry lists three groups: standard 10-day fidaxomicin, standard 10-day vancomycin followed by taper and pulse vancomycin, and standard 10-day vancomycin. Its stated purpose was to assess whether the first two regimens were superior to standard vancomycin treatment for recurrent Clostridium difficile infection.
The registry lists enrollment of 308, a start date of 2016-02-19, and a primary completion date of 2024-08-07. The study status is terminated. The reason for termination and the relationship, if any, between the status and the planned completion are not reported in the registry record. Status alone does not explain what happened to recruitment, follow-up, or outcome collection.
The parallel design assigns participants to treatment groups that are followed within their assigned regimen rather than describing a crossover. Randomization is intended to reduce systematic differences between groups at assignment. Double masking indicates that the record labels the study as masked, but does not specify who was masked or how masking was maintained.
The registry names 15 outcome measures and 0 analyses. It describes a primary modified intention-to-treat analysis and two sensitivity analyses for missing primary outcomes, but does not report comparative primary-outcome results. Allocation methods, eligibility criteria, treatment adherence, follow-up completeness, and the operational details of masking are 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
| Stage | Fidaxomicin | Vancomycin T/P | Vancomycin |
|---|---|---|---|
| STARTED | 105 | 102 | 101 |
| Modified Intent-To-Treat | 100 | 99 | 100 |
| Safety Set | 102 | 100 | 100 |
| COMPLETED | 84 | 91 | 94 |
| NOT COMPLETED | 21 | 11 | 7 |
Analysis population for the primary outcome, as defined in the registry: mITT Primary Analysis: Missing primary outcome D-COM at Day 59 in the mITT analysis was imputed by an imputation model. mITT Sensitivity Analysis 1: Missing primary outcome D-COM at Day 59 was treated as failure. mITT Sensitivity Analysis 2: Missing outcomes were excluded as a complete case analysis. PP analysis: Participants who 1) failed to respond by day 10 or completed day 59 follow-up and (2) took 80% of their assigned drug according to the pill count (Per-Protocol population).
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Fidaxomicin | Vancomycin T/P | Vancomycin | Total |
|---|---|---|---|---|---|
| Participants analysed | 105 | 102 | 101 | 308 | |
| Age, Continuous | years | 66.6 (SD 12.5) | 67.7 (SD 11.9) | 67.9 (SD 12.0) | 67.4 (SD 12.1) |
| Sex: Female, Male: Female | Participants | 12 | 6 | 11 | 29 |
| Sex: Female, Male: Male | Participants | 93 | 96 | 90 | 279 |
| Race/Ethnicity, Customized: White | Participants | 86 | 80 | 79 | 245 |
| Race/Ethnicity, Customized: African American | Participants | 15 | 18 | 19 | 52 |
| Race/Ethnicity, Customized: Other | Participants | 3 | 4 | 3 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Sustained Clinical Response as Measured at Study Day 59 for All Treatment Regimens, measured over Day 59 for all treatment regimens..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with sustained clinical response measured at study day 59 for all treatment regimens. The registry defines sustained response as symptom resolution during treatment without a listed adverse clinical outcome assessed on day 59: diarrhea recurrence, other non-fatal clinical events including severe abdominal pain, toxic megacolon or colectomy, or death.
This is a composite endpoint: a participant’s response depends on the combined definition rather than on symptom resolution alone. Composites can capture more than one way a treatment course may fail to meet the intended outcome, while also making interpretation dependent on the component events. The components may differ in clinical importance and frequency; component-specific results would help readers understand what contributes to the overall measure, but such results are not reported in the registry record.
Day 59 provides a common assessment point for the reported endpoint. The endpoint is expressed as a count of participants, so an analysis would ordinarily compare the proportions meeting the composite definition across groups. However, the registry record does not report group counts, an effect estimate, a confidence interval, or a test result for this primary outcome. The endpoint definition therefore clarifies what was intended to be measured, but does not by itself show how the groups compared.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record sets out a clinically focused question: whether two regimens are superior to standard vancomycin for recurrent Clostridium difficile infection. Its primary outcome is a composite sustained clinical response assessed at day 59. Yet the posted record does not include the primary outcome counts or a treatment comparison. It therefore does not allow readers to determine the observed direction, size, or precision of a difference among the regimens.
The record lists 15 outcome measures and 0 analyses. The named secondary outcomes include a sustained diarrhea composite at 28 days after the end of therapy, a Clostridium difficile infection composite, symptom resolution, CDI recurrence, diarrhea recurrence, health-related quality of life, and a strain-related sustained response. These outcome names describe areas assessed, but without reported results they cannot establish whether any group differed on them.
A treatment comparison is more informative when it includes an effect estimate and its uncertainty. A confidence interval describes a range of values compatible with the data and analysis assumptions; its width indicates precision. Neither an estimate nor a confidence interval for the primary outcome is reported in the registry record. A p-value or other inferential result is also not reported. Consequently, no conclusion about statistical evidence for superiority can be drawn from the registry entry alone.
The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such illustrations are planning calculations, not observed power and not evidence that a treatment effect was present. The record does not give the trial’s own sample-size justification, and the numerical planning results are not reported in the registry record.
The status is terminated, but the reason is not reported in the registry record. Termination can be relevant context for interpreting a trial, but the status alone does not show whether the primary outcome was collected, whether the planned comparisons were completed, or why the study ended. Those questions remain unresolved in the posted record.
For these reasons, the registry entry supports description of the intended design, outcome, and missing-data approaches, but not an efficacy conclusion. It also does not establish that a treatment is ineffective or that the groups were equivalent: absence of comparative results is not evidence of no difference. The available safety counts likewise require cautious interpretation, because counts without a causal assessment, group comparison, or detailed follow-up information cannot establish whether treatment caused an event.
9. Statistical Methods Explained
The record identifies a binary primary outcome expressed as a count of participants. For an outcome of this kind, the central descriptive quantity is the number meeting the endpoint in each group, often interpreted alongside the number assessed. A comparative analysis can then estimate how the groups differ. The registry record gives neither the group-specific primary outcome counts nor a comparative estimate, so those quantities cannot be interpreted for this trial.
What does randomization contribute?
Random assignment is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics at the time of assignment. It does not guarantee identical groups, especially in an individual study. The validity of a randomized comparison also depends on how assignments were generated and concealed, how participants were followed, and how outcomes were assessed. The record labels allocation as randomized, but the sequence-generation and concealment methods are not reported in the registry record.
The trial is described as double masked. Masking can reduce the influence of treatment expectations on participant reports, clinical decisions, and outcome assessment, depending on who is masked and how outcomes are determined. The registry record does not specify who was masked or how masking was maintained. The primary composite includes clinical events as well as symptom resolution, so knowing the operational approach to assessment would help readers judge potential measurement influences.
How should a confidence interval be read?
In general, a confidence interval expresses uncertainty around an estimated treatment contrast under the assumptions of the statistical method. A narrower interval indicates greater precision than a wider interval, while the values included indicate which effect sizes remain compatible with the analysis. An interval does not remove possible bias from missing data, outcome measurement, or deviations from the planned analysis. No primary-outcome confidence interval is reported in the registry record.
A p-value, in general, measures how compatible observed data are with a specified null hypothesis under the model used; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. A complete interpretation would consider the estimated effect and its uncertainty as well as any test result. The registry record does not report a primary-outcome p-value or identify a reported comparative analysis.
What do the planning assumptions mean?
The record describes a sample-size planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. These are assumptions for a planning calculation, not a report of the trial’s original design justification. The registry record does not report the trial’s own sample-size justification.
Planning sample sizes are conditional on assumed effects and analysis choices. They do not say how likely a completed trial was to detect a true effect, and they are not observed power. The record’s illustration is based on an observed effect, but comparative primary-outcome estimates are not reported in the registry record. The numerical planning outputs are also not reported in the registry record, so no such values can be interpreted from the entry.
Why can over-dispersion matter?
In general, over-dispersion means that observed variability is greater than a statistical model assumes. If it is ignored, standard errors may be too small and confidence intervals too narrow, which can make evidence appear more precise than it is. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not describe a model for the primary outcome or report an assessment of over-dispersion, so its relevance to this trial cannot be determined from the entry.
The outcome is a composite, and the record describes imputation for missing primary outcomes in the primary modified intention-to-treat analysis. The model, variables, and assumptions used for imputation are not reported in the registry record. Those details matter because imputation uses assumptions about unobserved outcomes; different assumptions can lead to different estimates. The named sensitivity analyses address missing outcomes in alternative ways, but their results are not reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 15 outcome measures, including a primary sustained clinical response and several secondary outcomes. When a study evaluates multiple outcomes or comparisons, the chance of obtaining at least one apparently unusual result can increase if each is assessed independently. Statistical approaches can address multiplicity by defining a hierarchy, adjusting inference, or emphasizing a prespecified primary analysis. The hierarchy, any multiplicity adjustment, and the detailed testing plan are not reported in the registry record.
The primary modified intention-to-treat analysis is described as using an imputation model for missing day-59 outcomes. In sensitivity analysis 1, missing primary outcomes were treated as failures. In sensitivity analysis 2, missing outcomes were excluded in a complete-case analysis. These approaches answer the question under different assumptions: treating missing outcomes as failures assigns them an unfavorable status, while complete-case analysis uses participants whose outcomes are available. Neither approach alone resolves whether missingness could be related to outcome or treatment.
The imputation model and assumptions, the number of missing outcomes, and the results of the primary and sensitivity analyses are not reported in the registry record. The precise definition of the modified intention-to-treat population is also not reported. Details of other analysis populations and how participants were handled after randomization are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Fidaxomicin | 34 | 102 | 33.3% |
| Vancomycin T/P | 30 | 100 | 30.0% |
| Vancomycin | 27 | 100 | 27.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Fidaxomicin | 8 of 102 |
| Vancomycin T/P | 2 of 100 |
| Vancomycin | 3 of 100 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Fidaxomicin | 7 of 102 |
| Vancomycin T/P | 15 of 100 |
| Vancomycin | 12 of 100 |
Most frequent serious adverse event terms
| Event term | Organ system | Fidaxomicin | Vancomycin T/P | Vancomycin |
|---|---|---|---|---|
| Clostridium difficile infection | Infections and infestations | 5 of 102 | 6 of 100 | 3 of 100 |
| Urinary tract Infection | Infections and infestations | 2 of 102 | 4 of 100 | 2 of 100 |
| Pneumonia | Infections and infestations | 2 of 102 | 3 of 100 | 1 of 100 |
| Cardiac failure | Cardiac disorders | 2 of 102 | 2 of 100 | 1 of 100 |
| Acute kidney injury | Renal and urinary disorders | 2 of 102 | 1 of 100 | 2 of 100 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 102 | 1 of 100 | 2 of 100 |
| Clostridium difficile colitis | Infections and infestations | 1 of 102 | 3 of 100 | 0 of 100 |
| Suicidal ideation | Psychiatric disorders | 1 of 102 | 2 of 100 | 1 of 100 |
| Alcohol detoxification | Surgical and medical procedures | 2 of 102 | 1 of 100 | 1 of 100 |
| Bacteraemia | Infections and infestations | 2 of 102 | 1 of 100 | 0 of 100 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Fidaxomicin | Vancomycin T/P | Vancomycin |
|---|---|---|---|---|
| Hepatic enzyme increased | Investigations | 1 of 102 | 3 of 100 | 1 of 100 |
| Abdominal distension | Gastrointestinal disorders | 1 of 102 | 0 of 100 | 2 of 100 |
| Alanine aminotransferase | Investigations | 1 of 102 | 2 of 100 | 0 of 100 |
| Abdominal pain | Gastrointestinal disorders | 1 of 102 | 1 of 100 | 0 of 100 |
| Drug eruption | Skin and subcutaneous tissue disorders | 0 of 102 | 1 of 100 | 1 of 100 |
| Pruritis | Skin and subcutaneous tissue disorders | 1 of 102 | 0 of 100 | 1 of 100 |
| Fatigue | General disorders | 0 of 102 | 2 of 100 | 0 of 100 |
| Abdominal distension | Gastrointestinal disorders | 0 of 102 | 1 of 100 | 0 of 100 |
| Diarrhoea | Gastrointestinal disorders | 0 of 102 | 0 of 100 | 1 of 100 |
| Diarrhoea | Gastrointestinal disorders | 0 of 102 | 0 of 100 | 1 of 100 |
Serious events with the highest arm-level rate: clostridium difficile infection (6.0%), urinary tract infection (4.0%), pneumonia (3.0%), clostridium difficile colitis (3.0%), cardiac failure (2.0%).
The registry lists serious adverse event counts for each group: 34 affected among 102 at risk for fidaxomicin, 30 among 100 at risk for vancomycin T/P, and 27 among 100 at risk for vancomycin. It separately lists other adverse event counts of 7 among 102, 15 among 100, and 12 among 100, respectively. Death counts are listed as 8, 2, and 3 in the same group order. These are descriptive counts; the registry does not provide a causal assessment for the events.
The listed serious-event terms include Clostridium difficile infection at 6.0%, urinary tract infection at 4.0%, pneumonia at 3.0%, Clostridium difficile colitis at 3.0%, cardiac failure at 2.0%, and fall at 2.0%. The denominator and overlap between terms are not reported in the registry record, so these percentages should not be interpreted as mutually exclusive categories or combined into a total.
Counts alone do not account for differences in follow-up, event severity, timing, or participant characteristics. The record does not report comparative safety estimates, uncertainty intervals, or whether deaths were considered related to treatment. These figures therefore describe reported event counts, not proof that a regimen caused or prevented an event.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, double-masked, parallel phase 4 study was intended to compare three regimens for recurrent Clostridium difficile infection. It identifies standard 10-day fidaxomicin, standard 10-day vancomycin followed by taper and pulse vancomycin, and standard 10-day vancomycin. It also defines a primary composite outcome of sustained clinical response measured at day 59.
What the record does not establish is whether either study regimen was superior to standard vancomycin. Primary outcome counts, effect estimates, confidence intervals, and test results are not reported in the registry record. Without those results, readers cannot assess the magnitude or precision of any difference. The absence of reported comparisons does not establish that there was no difference, equivalence, or lack of benefit.
The listed secondary outcomes and adverse event counts add context about what was assessed and what events were recorded, but they do not replace comparative outcome results. The safety counts do not establish causality, and the serious adverse event term percentages have no reported denominator or overlap information in the registry record.
The study status is terminated, but the reason and its implications for data collection or analysis are not reported in the registry record. The entry also does not include details needed to assess all sources of uncertainty, such as the imputation model, full analysis population definitions, or multiplicity strategy. These gaps limit interpretation of the intended methods and the clinical outcomes.
Accordingly, the defensible reading is descriptive: the registry records the study question, treatment groups, endpoint definition, some missing-data approaches, and safety counts. It does not report the evidence needed to judge comparative effectiveness or to quantify uncertainty around the primary outcome.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary outcome combines sustained symptom response with the absence of several clinically important events. A composite can summarize multiple ways an outcome may not be sustained, but interpretation depends on knowing how often each component occurred. Overall composite results and component-specific results are not reported in the registry record, leaving the endpoint definition clearer than the outcome evidence.
The record also names three approaches to missing primary outcomes: imputation in the primary modified intention-to-treat analysis, treating missing outcomes as failures in one sensitivity analysis, and excluding them in a complete-case analysis. These alternatives make visible an important analytic issue. Missing outcomes require assumptions, and comparing analyses under different assumptions can show whether conclusions are sensitive to those choices. Here, the imputation details and analysis results are not reported in the registry record.
Multiplicity matters because 15 outcome measures are listed. Without a stated outcome hierarchy or adjustment plan, readers cannot determine how the many outcomes were intended to support confirmatory claims. The record reports 0 analyses, so no comparative findings are available to evaluate.
Finally, the terminated status makes the distinction between study design and reported evidence especially important. The registry gives enrollment of 308 and lists safety counts, but does not report why the trial terminated or provide the primary comparison. The statistical value of the record is therefore in clarifying what was planned and what information remains unavailable, rather than in resolving whether the regimens differed.
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.
Several limitations specific to interpreting this trial arise from the registry record. It reports the primary endpoint definition but not the group-level day-59 counts, the treatment contrast, uncertainty intervals, or a test result. The number of outcome measures is listed as 15, while the number of analyses is listed as 0. As a result, the comparative findings and the analysis supporting them cannot be assessed from the registry entry.
The study is marked terminated, but the reason is not reported in the registry record. The record does not explain whether termination affected recruitment, follow-up, endpoint ascertainment, or planned analyses. Enrollment is listed as 308, but the relation between enrollment and the reported safety groups is not described. No conclusion about completeness of follow-up should be inferred from those entries alone.
Important design and analysis details are not reported, including eligibility criteria, allocation procedures, who was masked, the definition of the modified intention-to-treat population, and the imputation model. The record names sensitivity analyses but does not give their results. It also does not report a multiplicity strategy or the trial’s own sample-size justification.
Safety interpretation is limited because counts are not accompanied by comparative estimates or uncertainty, the relation of deaths to treatment is not stated, and denominators or overlap for the listed serious-event terms are not reported. These limitations constrain both the assessment of potential bias and the strength of any conclusion drawn from the registry entry.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Optimal Treatment for Recurrent Clostridium Difficile — NCT02667418.
- Registry record last updated 2026-08-21; status last verified 2026-07.
- Results first posted 2025-11-12.
- 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.
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18. Record Summary
NCT02667418, titled Optimal Treatment for Recurrent Clostridium Difficile, is listed as a phase 4 randomized, double-masked, parallel study sponsored by the VA Office of Research and Development. It enrolled 308 participants, started on 2016-02-19, had a primary completion date of 2024-08-07, and is marked terminated.
The three regimens were standard 10-day fidaxomicin, standard 10-day vancomycin followed by taper and pulse vancomycin, and standard 10-day vancomycin. The primary outcome was sustained clinical response measured at day 59. The record lists 15 outcome measures and 0 analyses.
It describes a modified intention-to-treat primary analysis using imputation for missing outcomes, with sensitivity analyses treating missing outcomes as failures and excluding them in a complete-case analysis. Comparative primary-outcome results and the reason for termination are not reported in the registry record.