A Prospective Trial of Frozen-and-Thawed Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Prospective Trial of Frozen-and-Thawed Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection (NCT02394275), a na phase 2 study. The primary outcome is No Recurrence of CDI-related Diarrhea.

2. Clinical Question

3. Trial Design

This was a prospective, open-label, multicentre phase 2 trial of frozen-and-thawed FMT for recurrent CDI. The registry record lists McMaster University as the sponsor, an enrollment of 140, and a status of terminated. The recorded start was 2014-03-01 and the primary completion date was 2016-09-01. The registry does not explain why the trial was terminated or provide details about the conduct of each participating centre.

The design is listed as single group, with allocation recorded as not applicable and masking recorded as none. The record therefore describes participants receiving the intervention without a randomized or other concurrent comparison arm. “Open-label” means that masking was not used; the record does not describe any separate blinded outcome assessment. Without a comparison group, outcomes cannot be contrasted with outcomes under another treatment within this trial.

The intervention was frozen-and-thawed FMT. The arm description states that material was stored at -20 oC and thawed before use. Participants taking antibiotics to control CDI were to stop them 24 hours before FMT. The registry does not report adherence to that instruction, the number of FMT administrations per participant, or variations in the intervention across centres.

The primary outcome was the number of participants with no recurrence of CDI-related diarrhea at 8 weeks following the last FMT, without an intervention specifically for recurrence. The outcome timeframe is listed as 13 weeks. The registry record does not explain the relationship between that timeframe and the stated 8-week assessment point. Safety of FMT is listed as a secondary outcome. Although the brief summary describes other objectives, detailed results for those objectives 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.

Before assignment: Participants must have laboratory diagnosis of recurrent CDI based on Society for Healthcare Epidemiology of America definition, recurrence defined as return of diarrhea and positive stool test after period of symptom resolution within 8 weeks of the first episode and has received at least 10-day course of oral vancomycin. Eligible participants at time of screening will discontinue antibiotic 24 to 48 hours prior to receiving FMT

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.

Population: 18 years or older with a history of recurrent CDI

6. Primary Endpoint

The registry lists the primary outcome as No Recurrence of CDI-related Diarrhea, measured over 13 weeks.

The primary endpoint is a count of participants who meet a defined clinical condition: no recurrence of CDI-related diarrhea at 8 weeks following their last FMT, without antibiotics or additional FMT specifically for recurrence. It is binary at the participant level. A participant either satisfies the endpoint definition or does not. The endpoint title describes the favorable state, while the registry’s outcome type indicates that the intended measure is a number of participants, not a continuous score or a rate over time.

This kind of outcome can be useful because it translates follow-up into a clinically interpretable status for each participant. The restriction on interventions for recurrence is part of the definition: an absence of diarrhea alone would not satisfy the endpoint if the participant needed an intervention specifically for recurrence. The timing is also important. The endpoint refers to 8 weeks after the last FMT, while the listed timeframe is 13 weeks. The record does not clarify how these timing descriptions fit together.

The endpoint result, denominator, and method for handling participants with incomplete follow-up are not reported in the registry record. Therefore, no response proportion, uncertainty interval, or comparison with another treatment can be stated. General statistical context: a binary endpoint can be summarized by the number meeting the definition and the number assessed, but the meaning of that summary depends on clearly defined follow-up and analysis populations.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record reports a binary primary outcome and a single-group design, but no analysis of that outcome. The concepts below are general statistical explanations, not a description of methods confirmed for this trial. The statistical analysis plan is not reported in the registry record.

What does a binary endpoint represent?

A binary endpoint classifies each participant into one of two states under a prespecified definition. Here, the stated favorable state is no recurrence of CDI-related diarrhea at 8 weeks following the last FMT without an intervention specifically for recurrence. A count of participants meeting that definition is interpretable only alongside the number assessed and a clear description of who was included. Neither the primary outcome count nor its analysis denominator is reported in the registry record.

Binary outcomes are often summarized as counts and proportions. A proportion requires a numerator—the participants meeting the endpoint—and a denominator—the participants included in the analysis. Neither can be reconstructed from enrollment or safety figures, since those may refer to different populations and follow-up. No calculation should substitute the listed enrollment or safety denominator for the missing primary outcome denominator.

Why does the single-group design matter?

A single-group study can describe outcomes observed among participants receiving an intervention. It does not provide an internal estimate of what would have happened to comparable participants under a different treatment. An external benchmark might sometimes be used in a study, but the registry record does not report one or describe a comparison against one. A before-and-after contrast would require measurements and an analysis plan; neither is reported as a primary analysis.

General statistical context: causal comparisons require a credible basis for comparing outcomes under different treatment conditions. Random allocation can help make groups comparable on average, while a well-designed nonrandomized comparison needs other safeguards against confounding. This record lists no allocation and describes one group, so treatment effects relative to a control cannot be derived from the design fields.

What can uncertainty estimates tell readers?

A confidence interval is a range of values compatible with an estimate under the assumptions of the analysis. Its width reflects statistical precision: less precise estimates generally have wider intervals. For a binary endpoint, an interval for a proportion would depend on the observed count, the denominator, and the interval method. No primary outcome estimate or interval is reported in the registry record, so precision cannot be evaluated.

A p-value, when used, describes how unusual the observed data would be under a specified null hypothesis and statistical model. It does not directly measure the probability that a treatment works, nor does it establish the importance of an effect. The registry record reports no primary analysis or p-value. It would be inappropriate to infer one from the design or from safety counts.

How should timing be interpreted?

The endpoint description places the assessment at 8 weeks following the last FMT, whereas the outcome timeframe is listed as 13 weeks. The registry record does not explain whether the timeframe refers to an overall observation window, an administrative schedule, or another feature of the endpoint. These descriptions should not be reconciled by assumption. The exact assessment schedule, rules for participants receiving additional FMT, and handling of events outside the stated interval are not reported in the registry record.

General statistical context: time-to-event methods can account for different follow-up durations and censoring, while a fixed-time binary endpoint classifies status at a defined assessment point. Choosing between these approaches requires knowing when events occurred, how follow-up ended, and the planned analysis. The record identifies a participant count as the primary measure and gives no time-to-event analysis.

What does open-label status imply?

Open-label means masking was not used, as also reflected by masking recorded as none. In general, knowledge of treatment assignment can affect participant reports, care decisions, and outcome assessment, depending on how an endpoint is measured and who assesses it. The registry record does not describe blinded adjudication or other safeguards for outcome assessment. This does not establish that bias occurred; it identifies a design feature relevant to interpretation.

Can the safety data be treated as a comparative analysis?

No comparative safety estimate is reported. General statistical context: event counts are easier to interpret when the at-risk population, observation period, event definitions, and ascertainment procedures are clear. Exposure duration and recurrent events can also matter. The registry lists safety counts and terms, but does not report those details or a control group. The counts are descriptive registry entries, not estimates of a treatment-attributable risk difference.

In sum, the record provides design and endpoint definitions but not the planned statistical methods or primary outcome analysis. The statistical analysis plan, methods for missing observations, and any adjustment strategy are not reported in the registry record. General methodological explanations cannot fill those gaps or establish which analyses the investigators performed.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a prespecified hierarchy of outcomes, or adjustments for multiple testing. The brief summary describes several objectives, including clinical response, treatment failure, relapse, safety, health and well-being, feasibility, and metagenomics in selected patients. The record does not report analyses for these objectives. Without analysis details, it is not possible to determine which outcomes were formally tested, whether any testing was exploratory, or how multiplicity was addressed.

The primary outcome is defined, but its result, analysis denominator, and missing-data handling are not reported in the registry record. The record does not say how participants with incomplete follow-up, withdrawal, death, or additional treatment were classified for the primary endpoint. It also does not identify an intention-to-treat, per-protocol, or other analysis population. These omissions matter because different rules for inclusion and missing outcomes can produce different summaries.

General statistical context: missing outcome data can affect both the estimated event frequency and its precision, particularly when absence of follow-up is related to a participant’s health or treatment course. A transparent report ordinarily states how much data are missing, why, and how missing values are handled. No such account is reported in the registry record. The safety count of participants at risk cannot be assumed to be the primary analysis denominator.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary tract infection (3.0%), clostridium difficile infection (2.3%), congestive heart failure (1.5%), acute kidney injury (1.5%), pneumonia (1.5%).

The safety information lists a single group with 133 participants at risk. It reports 16 serious adverse events, 11 other adverse events, and 11 deaths. The registry record does not define how these categories were collected, whether the event counts represent participants or event episodes, or whether a participant could contribute to more than one category. The counts should therefore be read as the recorded safety figures, not as mutually exclusive participant groups.

The listed serious adverse-event terms and percentages are urinary tract infection, 3.0%; Clostridium difficile infection, 2.3%; congestive heart failure, 1.5%; acute kidney injury, 1.5%; pneumonia, 1.5%; and arrhythmia, 0.8%. These are registry-listed percentages; the record does not provide the corresponding term-specific counts or additional detail about event timing, severity, duration, or relationship to FMT.

The 11 deaths are reported in the same safety group, but their causes, timing, and relationship to treatment are not reported in the registry record. The figures also lack a comparison group and exposure-adjusted analysis. General statistical context: a count or percentage describes reported events in a defined group; it does not by itself show whether treatment caused an event or how the rate compares with another treatment. The safety entries should be interpreted descriptively.

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

The registry record documents a prospective, open-label, single-group phase 2 trial of frozen-and-thawed FMT for recurrent CDI. It defines a primary endpoint focused on no recurrence of CDI-related diarrhea at 8 weeks following the last FMT without an intervention specifically for recurrence. It also records safety information. These details show what the trial was designed to examine and what safety figures were entered in the registry.

The primary endpoint result is not reported in the registry record. There is no posted count of participants meeting the endpoint, analysis denominator, confidence interval, or statistical test. The record therefore does not show the frequency of the defined outcome or how precisely it was estimated. It also cannot establish whether the outcome was more or less frequent than it would have been under another treatment.

The single-group design has no concurrent comparator in the recorded design fields. Even if an outcome estimate were available, an observed result in one group would not by itself separate treatment effects from the course of illness, participant selection, other care, or changes over time. This is a limitation on causal interpretation, not evidence that a treatment effect did or did not occur.

The safety figures indicate that adverse events and deaths were recorded, but the registry does not report event-level circumstances or a comparison group. They cannot be used to attribute events to FMT or to estimate a comparative safety effect. The trial’s terminated status is recorded, but the reason for termination is not reported in the registry record and should not be inferred from the status alone.

General statistical context: the strength of a conclusion depends on the outcome definition, completeness of follow-up, precision of estimates, and suitability of the design for the question. Here, several of those elements—including the primary result and missing-data methods—are not reported. The record supports a description of the study and its available safety entries, but not a conclusion about efficacy, comparative benefit, or treatment-attributable harm.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly stated clinical endpoint and a reported result. The registry defines a participant-level outcome tied to both a follow-up time and the absence of additional intervention for recurrence. Those details matter: a binary outcome is only interpretable when the event definition and assessment point are understood. The registry’s 13-week timeframe alongside the endpoint’s 8-week assessment description also illustrates why timing should be reported unambiguously.

The design is equally important. A prospective, open-label study can collect structured information about outcomes in a treated group, but a single-group design does not provide a concurrent treatment contrast. Readers must distinguish description of outcomes from estimation of comparative treatment effects. The registry’s use of “controlled” in its brief summary does not change the design fields, which describe one group and no allocation.

The available safety entries also show why counts need context. Counts and listed percentages are useful descriptions, but interpretation depends on event definitions, follow-up, at-risk denominators, and whether events are attributed to treatment. The registry does not report all of those details or a comparison group. The entries cannot answer a comparative safety question by themselves.

Finally, this record highlights the value of reporting analysis populations, missing-data methods, uncertainty estimates, and reasons for trial termination. Their absence limits evaluation of the primary outcome and the precision of any estimate. The record describes a clinically focused question and records safety information, while leaving key information needed for statistical interpretation unreported.

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 most consequential limitation for interpreting the primary endpoint is that its result is not reported in the registry record. The primary outcome count, denominator, analysis population, and uncertainty estimate are absent. The registry also does not report methods for incomplete follow-up, withdrawal, or death in relation to that endpoint, so the effect of missing outcome information cannot be assessed.

The single-group design provides no concurrent control comparison. Masking is recorded as none, and the record does not describe independent or blinded outcome assessment. These design features limit the ability to distinguish treatment-associated outcomes from other influences or to assess possible effects of knowledge of treatment on outcome measurement. They do not establish that bias occurred.

The endpoint description refers to 8 weeks following the last FMT, while its timeframe is listed as 13 weeks. The registry does not explain how these timing statements relate. It also does not report the number of administrations, adherence, or centre-specific treatment details. These gaps make it difficult to assess consistency of intervention delivery and follow-up.

The safety information lacks event-level details, timing, exposure duration, and a comparator. The record does not explain the relationship between the reported deaths and treatment, or whether adverse-event counts refer to participants or event episodes. The reason for the trial’s terminated status is not reported in the registry record. The statistical analysis plan, sample-size justification, and methods for multiplicity are also not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Prospective Trial of Frozen-and-Thawed Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection — NCT02394275.
• Registry record last updated 2021-10-26; status last verified 2021-10.
• Results first posted 2021-10-26.
• 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 registry describes a prospective, open-label, multicentre phase 2, single-group trial of frozen-and-thawed FMT for recurrent CDI. It lists McMaster University as sponsor, enrollment of 140, and status as terminated. The primary endpoint is no recurrence of CDI-related diarrhea at 8 weeks following the last FMT without an intervention specifically for recurrence; the listed timeframe is 13 weeks.

The primary endpoint result and its analysis details are not reported in the registry record. The safety entry lists 133 participants at risk, 16 serious adverse events, 11 other adverse events, and 11 deaths. The record does not provide a concurrent comparator, a statistical analysis plan, or enough event-level detail to support comparative or causal conclusions. The reason for termination is not reported in the registry record.