Dose Ranging Study of the Safety and Efficacy of Orally Administered Lyophilized Fecal Microbiota Product (PRIM-DJ2727) for the Treatment of Recurrent Clostridium Difficile Infection (CDI): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose Ranging Study of the Safety and Efficacy of Orally Administered Lyophilized Fecal Microbiota Product (PRIM-DJ2727) for the Treatment of Recurrent Clostridium Difficile Infection (CDI) (NCT03298048), a randomized phase 2 study. The primary outcome is Safety as Assessed by Number of Participants With Nausea.

2. Clinical Question

3. Trial Design

This was a phase II, randomized, triple-masked, parallel-group dose-ranging study of PRIM-DJ2727 for recurrent C. difficile infection. The registry describes three biological intervention groups: low, mid, and high fecal microbiota doses. In a parallel design, participants are assigned to a group and outcomes are considered across the groups; the record does not describe switching between doses. Randomization means that assignment is by chance, but the method used to generate or conceal assignments is not reported in the registry record.

The listed dose descriptions distinguish the groups by the amount of source stool used to collect the healthy microbiota product across 2 consecutive treatment days. For the low dose, the description is product collected from 50g stool on each day. For the mid dose, it is product collected from 100g stool on the 1st day and 50g stool on the 2nd day. For the high dose, it is product collected from 100g stool on each day. The registry does not report further details about product preparation, administration procedures, or adherence.

The trial enrolled 17 participants. The posted primary-outcome group sizes are 4 for low dose, 3 for mid dose, and 8 for high dose. These are small groups, so each participant’s outcome contributes substantially to the observed count in that group. The record does not explain the difference between the overall enrollment and the group sizes reported for this outcome.

The study began on 2017-12-21, had a primary completion date of 2019-03-30, and is listed as terminated. The reason for termination, whether recruitment ended as planned, and whether the recorded completion date reflects follow-up for all participants are not reported in the registry record. Triple masking is recorded, but which parties were masked and how masking was maintained are not reported.

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: 2 of the 17 enrolled did not start treatment: one did not start treatment due to physician's concerns about patient taking bowel prep, and the second did not start treatment because of hospitalization.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Safety as Assessed by Number of Participants With Nausea, measured over 180 days.

The primary endpoint is safety assessed as the number of participants with nausea during 180 days. It is a binary participant-level outcome: a participant either was or was not counted as having nausea over the stated timeframe. It does not count repeated episodes, quantify symptom intensity, or describe when nausea occurred. Those details are not reported in the registry record.

A participant count is useful for describing how many people in each group experienced a specified event. In a dose-ranging safety study, comparing such counts across assigned dose groups can help characterize the pattern of recorded events. However, a count alone does not establish why an event occurred or whether the dose caused it. Participants may differ in ways that affect outcomes, and the registry record does not provide enough detail to assess those factors.

The posted nausea counts are 0 in the low-dose group, 2 in the mid-dose group, and 1 in the high-dose group. The corresponding group sizes are 4, 3, and 8. No confidence intervals, adjusted estimates, or statistical test for this endpoint are reported in the registry record. The data therefore describe the recorded participant counts, but do not give a reported estimate of the uncertainty around a dose-group comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is registered as randomized, triple-masked, and parallel, with three dose groups. These design features describe how the study was organized, but they do not supply the missing details of its statistical analysis. The registry record does not report the randomization procedure, which parties were masked, or the planned statistical methods for comparing outcomes.

What does randomization contribute?

In general, randomization assigns participants to groups by chance. It is intended to reduce systematic differences between groups at the time of assignment, including differences that investigators may not have measured. Randomization does not guarantee that groups will be alike, particularly in a small study. Here, the registry reports enrollment of 17 participants and primary-outcome group sizes of 4, 3, and 8. It does not report baseline characteristics or the allocation sequence, so balance between groups cannot be assessed from the registry entries.

Masking is intended, in general, to limit the influence of knowledge about assigned treatment on care, event reporting, or outcome assessment. The registry labels the study triple-masked, but does not identify the masked parties or describe how masking was implemented. For an outcome such as nausea, the method used to ask about and record symptoms could matter to interpretation. That method is not reported in the registry record.

How should a binary participant count be read?

The primary measure counts participants with nausea. In general, a binary endpoint records whether each participant experienced an event within a defined period. It differs from an event count, which could count multiple episodes for one person. The registry names a 180-day timeframe, but does not give the event definition, ascertainment schedule, or rules for counting a participant with repeated symptoms. The posted counts therefore communicate the number of participants recorded as having nausea, without describing frequency or severity.

When comparing binary outcomes, an analysis may estimate a difference or ratio between groups and quantify uncertainty with a confidence interval. A statistical test may also be used under a stated model. Those methods require a specified estimand and analysis plan, and their results depend on the assumptions and data included. The registry record reports no analyses for the outcomes, and no comparative estimate, confidence interval, or test result is available. No new contrast should be inferred from the counts alone.

Small groups make estimates sensitive to individual outcomes. In general, with few participants, adding or removing one event can substantially change a group’s observed event frequency. This is a reason to focus on the raw counts and to look for uncertainty estimates and analysis details, rather than treating a visual difference in counts as conclusive. No confidence intervals are reported for the nausea endpoint.

What do the dose groups allow researchers to ask?

A dose-ranging design can examine whether outcomes vary across dose levels. General interpretation depends on the doses being defined clearly and on having an analysis that tests or estimates the relevant pattern. The registry descriptions distinguish low, mid, and high groups by the stool amounts from which the product was collected over 2 treatment days. The registry does not report a planned dose-response model, a prespecified trend test, or a method for selecting an optimal dose. The observed nausea counts do not form a steadily increasing sequence across the three groups, but there is no reported analysis of a dose trend.

The registry’s planning description states that sample-size illustrations use the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. It also distinguishes participant counts per arm from total event counts for time-to-event outcomes. These are planning assumptions, not evidence that the trial had a particular probability of detecting an effect. The registry record does not report a trial-specific sample-size justification or the numerical planning results. Such illustrations are not observed power and do not establish the adequacy of the enrolled sample for a particular comparison.

The primary outcome is a count-based binary endpoint, while the registry also lists recurrent C. difficile infection as a secondary outcome. The registry entries do not describe whether that secondary outcome was analyzed as a binary event, a time-to-event measure, or another form of endpoint. The registry lists 6 outcome measures and no analyses. The analytic methods, definitions, and results for the remaining outcome measures are not reported in the registry record.

Why do missing-data and population rules matter?

In general, an analysis needs to state which participants are included and how incomplete outcome observations are treated. An intention-to-treat approach, for example, has a specific meaning and should not be assumed unless it is reported. Other approaches may use participants with observed outcomes or apply explicit missing-data methods. The registry record does not identify an analysis population or missing-data procedure, nor does it explain whether the posted group sizes represent all randomized participants or only those with outcome data.

Because no comparative analyses are posted, there is no reported adjustment for baseline factors, no multiplicity procedure, and no account of model diagnostics. This does not demonstrate that such methods were absent from the study’s internal analysis; it means they are not reported in the registry record. The counts can be described as posted, but the inferential framework behind them cannot be reconstructed from the available information.

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("Low Fecal Microbiota Dose", "Mid Fecal Microbiota Dose", "High Fecal Microbiota Dose")
n      <- c(4, 3, 8)
events <- c(0, 2, 1)
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  Low Fecal Microbiota Dose  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Mid Fecal Microbiota Dose  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2
ARM  High Fecal Microbiota Dose  8  1  12.5  0.3  52.7  2.2  47.1  2.8  48.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists recurrent C. difficile infection as a secondary outcome and reports 6 outcome measures overall. It does not provide comparative analyses for those outcomes. The primary outcome is nausea over 180 days. The number of hypotheses planned for testing, their prespecified order, and any adjustment for multiple comparisons are not reported in the registry record.

Multiplicity matters in general when several outcomes, doses, or comparisons are tested. Each additional statistical test can increase the chance of at least one apparently unusual result under a setting where there is no true difference. Methods such as adjusting significance thresholds or prioritizing a primary comparison can address that issue, but no such approach is reported. Since no analyses are reported, there are no posted p-values to interpret in light of multiplicity.

Missing-data procedures and analysis populations are also not reported. The primary endpoint’s timeframe is 180 days, but the record does not state how many participants completed that period, whether all participants had outcome observations, or how incomplete follow-up was handled. The group sizes associated with the posted nausea counts are 4, 3, and 8; the record does not explain whether these are randomized, treated, or outcome-evaluable populations.

These gaps matter because estimates can depend on which participants are included and on how missing outcomes are treated. The registry does not identify an intention-to-treat or per-protocol analysis, or any imputation or sensitivity analysis. Those methods should not be inferred from the posted counts. The registry record also does not report whether an interim analysis was planned or conducted.

12. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization (25.0%).

The registry reports serious adverse events separately from other adverse events. For serious adverse events, the low-dose group lists 1 affected participant among 4 at risk; the mid-dose group lists 0 among 3, and the high-dose group lists 0 among 8. Deaths are listed as 0 in all three groups. These are counts over the adverse-event reporting period recorded in the registry; the specific period and event-level details are not reported in the registry record.

The registry also lists hospitalization as a serious adverse-event term at 25.0%. The denominator and the relationship between that term and the group-level counts are not specified in the registry record for interpretation, so that percentage should not be treated as a group-specific rate. The record lists other adverse events affecting 1 participant in the low-dose group, 3 in the mid-dose group, and 6 in the high-dose group. The terms, severity, duration, and overlap between participants are not reported.

Adverse-event counts describe events recorded during the study; they do not alone establish that an event was caused by an assigned dose. Group sizes are small, and no comparative safety analysis or uncertainty estimate is reported. The serious-event counts should therefore be read descriptively, alongside the stated denominators, rather than as a reliable ranking of dose safety.

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

The results establish a descriptive record of nausea counts across the three dose groups: 0 of 4 in the low-dose group, 2 of 3 in the mid-dose group, and 1 of 8 in the high-dose group over the 180-day timeframe. They also show that the registry lists 1 serious adverse event in the low-dose group and none in the other groups, with 0 deaths in each group. These are the posted observations for the outcomes described.

They do not establish that the dose groups differ statistically. No comparative analyses, confidence intervals, or p-values are reported in the registry record. With these small group sizes, the observations have limited precision, and the result could be sensitive to individual participants. The registry also does not report enough information about missing outcomes or analysis populations to determine whether the counts cover every enrolled participant.

The results do not answer whether PRIM-DJ2727 reduces recurrence of C. difficile infection. Recurrence is listed as a secondary outcome, but no comparative result for it is reported in the registry record for interpretation. Nor do the nausea counts describe the number of symptom episodes, symptom intensity, or event timing. The primary outcome is a safety measure, not a direct measure of treatment efficacy.

The study’s termination status does not, by itself, explain why it ended or what effect termination had on the data collected. The reason for termination and any impact on follow-up are not reported in the registry record. Likewise, the registry’s triple-masking label does not disclose which people were masked or how that process worked.

In general, a randomized design can support a causal comparison when the study is appropriately conducted and analyzed, but the design label alone is not enough to establish a treatment effect. Interpretation also requires outcome definitions, analysis methods, follow-up completeness, and uncertainty estimates. Those elements are not reported for comparative results. The posted data therefore support a limited descriptive reading, not a conclusion about efficacy, optimal dose, or causal safety differences.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the gap between a randomized design and a reportable comparative result. The registry describes a randomized, triple-masked, parallel phase II study with three dose groups, but reports no analyses. The primary outcome counts can be read directly, yet they do not provide an estimate of how much groups differ or how uncertain that difference is.

The enrollment of 17 and the group sizes of 4, 3, and 8 make the importance of precision especially clear. In general, small samples can yield unstable estimates because individual outcomes have considerable influence. A dose-ranging study may be designed to explore patterns across groups, but such patterns need an analysis plan and uncertainty assessment. Neither a dose-response analysis nor a method for selecting an optimal dose is reported in the registry record.

The case also illustrates why outcome definition and reporting details matter. The primary measure counts participants with nausea over 180 days, while recurrence appears as a secondary outcome. These outcomes address different questions. A safety count cannot substitute for a recurrence analysis, and a listed secondary outcome without comparative results does not support an efficacy interpretation.

Finally, trial status and reported outcomes should be kept distinct. The registry lists the study as terminated, but does not report why. The design, observed counts, and missing analysis details each contribute to interpretation, and none alone fills in the others. For statistical readers, this makes clear why raw counts, study design, missingness, analysis populations, and uncertainty all need to be considered together.

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 enrolled sample was 17, and the primary-outcome group sizes were 4, 3, and 8. Such small groups limit the precision with which group-specific event patterns can be characterized. The registry reports no confidence intervals or comparative statistical analyses, so uncertainty around differences cannot be assessed from the posted results.

The registry lists the study as terminated but does not report the reason. It also does not explain whether enrollment or follow-up ended earlier than planned, whether all participants completed the 180-day timeframe, or how termination affected the analysis. These details are important when judging completeness, but are not reported in the registry record.

The nausea outcome is described as the number of participants with nausea. Event definition, collection method, severity grading, episode frequency, and timing are not reported. The adverse-event figures likewise lack detailed event descriptions and a stated reporting period in the registry record for interpretation. Hospitalization is listed at 25.0% among serious adverse-event terms, but the relevant denominator is not specified.

Baseline characteristics, eligibility criteria beyond recurrent C. difficile infection, and analysis populations are not reported. The registry does not identify how missing outcome data were handled, whether the posted group sizes represent all randomized participants, or whether any adjustment was planned. The identities of masked parties and the methods used to maintain masking are also not reported.

Finally, recurrence is listed as a secondary outcome, but no comparative result is available. The record does not report a sample-size justification, prespecified dose-response method, multiplicity procedure, or interim-analysis plan. These limitations constrain interpretation to the descriptive counts and design features recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dose Ranging Study of the Safety and Efficacy of Orally Administered Lyophilized Fecal Microbiota Product (PRIM-DJ2727) for the Treatment of Recurrent Clostridium Difficile Infection (CDI) — NCT03298048.
• Registry record last updated 2020-03-06; status last verified 2020-02.
• Results first posted 2020-03-06.
• 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

NCT03298048 is a phase II randomized, triple-masked, parallel dose-ranging study of orally administered lyophilized fecal microbiota product, PRIM-DJ2727, for recurrent C. difficile infection. It lists low, mid, and high dose groups and an enrollment of 17. The primary outcome is the number of participants with nausea over 180 days.

The posted nausea counts were 0 among 4 participants in the low-dose group, 2 among 3 in the mid-dose group, and 1 among 8 in the high-dose group. Recurrent C. difficile infection is listed as a secondary outcome. No comparative analyses are reported in the registry record. Serious adverse events are listed for 1 participant in the low-dose group and none in the other groups; deaths are listed as 0 in each group.

The trial began on 2017-12-21, had a primary completion date of 2019-03-30, and is listed as terminated. The reason for termination, analysis populations, missing-data methods, and comparative statistical results are not reported in the registry record.