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 Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease (NCT02765256), a randomized phase 2 study. The primary outcome is Change in Disease Activity by Harvey Bradshaw Index.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02765256 |
| Phase | Phase 2 |
| Condition | Crohn's Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 8 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Pennsylvania |
| Results posted | Yes |
2. Clinical Question
Population
People with active Crohn’s disease described as refractory to conventional, immunosuppressive therapy. The registry record does not give a more detailed population description in the primary outcome entry.
Intervention
A gut microbiota-targeted regimen involving bowel lavage and antibiotics, with fluconazole as the antifungal component. The intervention list also names vancomycin, neomycin, ciprofloxacin, polyethylene glycol 3350, and promethazine.
Comparator
The same general regimen with fluconazole placebo in place of fluconazole. The record identifies the arms as Fluconazole and Placebo.
Primary question
What was the change in disease activity, measured by Harvey-Bradshaw Index score, from the enrollment visit to Day 15, and how did the posted arm summaries compare?
The trial’s stated aim was to assess the effect of a novel gut microbiota-targeted therapeutic regimen in active Crohn’s disease that had not responded to conventional immunosuppressive therapy. The central contrast was the addition of fluconazole versus placebo alongside bowel lavage and antibiotics. This means the arm comparison addresses the regimen with and without the antifungal component, rather than comparing the whole treatment package with no treatment.
The primary outcome was change in Harvey-Bradshaw Index (HBI) score between enrollment and Day 15. The record describes the HBI as a clinical score based on general well-being, abdominal pain, abdominal mass, complications, and liquid bowel movements in the previous day. It identifies a score of 3 or lower as remission and a score of 8 or higher as severe disease. These thresholds provide context for the score, but the posted arm results are changes in score, not counts of participants who entered remission or had severe disease.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group phase 2 trial. The registry record gives enrollment as 8 and status as completed. It records a start of 2016-08 and primary completion in 2018-12. The sponsor was the University of Pennsylvania. These design and administrative details describe how the study was registered; they do not establish the size or precision of an effect.
Participants were assigned to a Fluconazole arm or a Placebo arm. The arm descriptions indicate that both groups received a regimen including vancomycin, neomycin, ciprofloxacin, and polyethylene glycol 3350, with fluconazole in one arm and fluconazole placebo in the other. The trial description characterizes the approach as bowel lavage and antibiotics with or without an antifungal. The registry record lists promethazine among the interventions, but does not explain its role in the brief summary.
Randomization is intended to make treatment assignment independent of participants’ characteristics on average, while masking is intended to reduce the influence of treatment knowledge on care, reporting, or assessment. With a small enrolled group, randomization cannot ensure that characteristics were balanced between arms. The registry record does not report the allocation sequence method, how masking was implemented, or whether masking remained successful.
The primary endpoint was change in HBI score from the enrollment visit to Day 15. The registry record also lists change in high-sensitivity C-reactive protein and safety and tolerability based on medication side effects and/or adverse events as secondary outcomes. It records four outcome measures overall, but does not give a full set of posted comparative analyses for them. The trial’s detailed protocol, eligibility criteria, and statistical plan 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 | Fluconazole | Placebo |
|---|---|---|
| STARTED | 4 | 4 |
| COMPLETED | 4 | 4 |
| NOT COMPLETED | 0 | 0 |
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 | Fluconazole | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 4 | 8 | |
| Age, Continuous | years | 44 (26 to 54) | 32.5 (20 to 66) | 39.5 (20 to 66) |
| Sex: Female, Male: Female | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Male | Participants | 3 | 4 | 7 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | participants | 4 | 4 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Disease Activity by Harvey Bradshaw Index, measured over enrollment visit (baseline) and 15 days.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | score on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint measures change in disease activity using the Harvey-Bradshaw Index (HBI), comparing the enrollment visit with Day 15. The HBI combines clinical information: general well-being, abdominal pain, abdominal mass, complications, and the number of liquid bowel movements in the previous day. A lower score represents a lower level of the measured clinical score. Accordingly, a negative change indicates a lower Day 15 score than the enrollment score, without by itself establishing why the score changed.
The registry record gives the outcome unit as a score on a scale and says the result is summarized by the median and full range. A median describes the middle observation in an ordered set of results. The full range reports the lowest and highest observed values, giving a sense of how far apart the individual values were. Neither summary reveals the exact pattern of every participant’s change.
The record identifies a score of 3 or lower as remission and a score of 8 or higher as severe disease. Those are thresholds for HBI scores, not for the change scores reported by arm. The posted results do not state how many participants met either threshold at enrollment or Day 15, nor how many changed from one category to another.
HBI is used as a clinical disease-activity measure, but a change in its score is not the same as a direct measure of intestinal inflammation or of every aspect of Crohn’s disease. The registry’s other listed outcomes include high-sensitivity C-reactive protein and safety and tolerability, but their role does not alter the definition of the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry posts a median HBI change of -5.0 in the Fluconazole arm, with a full range from -7.0 to 0.0. In the Placebo arm, the median change is -3.0, with a full range from -8.0 to -2.0. These are arm-level summaries of change from enrollment to Day 15. Negative changes indicate lower HBI scores at Day 15 than at enrollment.
The ranges overlap: some values in each arm lie within the span of values in the other. The observed medians differ, but the summaries alone do not show whether an arm difference is distinguishable from variability among participants. The registry record does not report a formal between-arm estimate, confidence interval, or p-value for this primary outcome. It also does not provide individual participant results, which would be needed to examine the distribution and patterns of change in detail.
Each arm’s posted outcome count is 4. A median and a range based on a small number of observations can be sensitive to individual values. The full range is not a confidence interval: it describes the observed extremes, not the uncertainty around an estimated treatment contrast. The medians should therefore be read as descriptive summaries of this trial rather than precise estimates of what would be expected in a broader population.
The primary endpoint description states that participants who withdraw for any reason before Day 15 will be considered treatment failures. The record does not report whether anyone withdrew before Day 15 or how that rule was applied in producing the posted summaries. The summaries therefore cannot be used to reconstruct the handling of missing measurements or to confirm the analysis population.
The registry record reports no posted analysis rows. The absence of a reported comparative analysis means there is no registry-based inferential result to use for judging the uncertainty of the arm contrast. It does not establish that no analysis was conducted outside the registry. Likewise, the record’s completion status does not itself indicate the direction, magnitude, or certainty of a treatment effect.
The secondary outcomes include change in high-sensitivity C-reactive protein and safety and tolerability based on side effects and/or adverse events. The record does not provide complete comparative results for those outcomes in the registry record for this interpretation. Any conclusion should remain limited to the descriptive primary outcome summaries and the safety counts that are posted, rather than extending them to other outcomes or to clinical benefit.
9. Statistical Methods Explained
What does the median describe? The median is the central value after observations are ordered. Unlike the arithmetic mean, it is not pulled as strongly by an unusually high or low observation. It can be a useful descriptive summary when outcome values are skewed or when a few observations may be far from the rest. In this trial, the posted primary result uses a median change in HBI score for each arm. The median does not describe every participant’s response, and the same median can arise from different underlying distributions.
What does the full range describe? A full range gives the smallest and largest observed values. For the primary outcome, the registry reports the range alongside the median for each arm. The range helps show the spread among the observed changes, but it is strongly influenced by the extremes. It is not a measure of uncertainty about the median or about a difference between arms. A confidence interval serves a different purpose: in general, it gives a range of values compatible with the data and a specified statistical procedure, reflecting uncertainty in an estimate. No confidence interval for the primary arm contrast is reported in the registry record.
Why does the arm comparison require more than comparing medians? Two descriptive medians do not provide a formal test of an arm difference. An inferential comparison would need to account for the observations in both groups and would produce an estimate of the contrast with an assessment of its uncertainty. The registry record does not report such an estimate, test statistic, p-value, or confidence interval for the primary endpoint. It is therefore not possible to determine from the posted summaries alone how compatible the observed difference in medians is with chance variation under a specified model.
General statistical interpretation also depends on the study’s analysis plan: the planned estimand, handling of missing data, and choice of method can affect what a comparison means. Those details are not reported in the registry record. The primary outcome description does specify that withdrawal before Day 15 is treated as treatment failure, but the posted summary does not explain whether or how that rule contributed to the analysis.
Why is over-dispersion relevant in general? Over-dispersion occurs when the observed variability in data is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors may be too small and confidence intervals may be too narrow. This is a general consideration for statistical modeling, not a reported feature of this trial’s analysis. The registry record does not describe a model or report an over-dispersion assessment for the primary outcome.
What do the planning illustrations mean? Any sample-size illustrations associated with the results are planning calculations based on the observed effect, not the trial’s original design or an observed measure of power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. Such calculations describe how a future study might be planned under those assumptions. They do not show that the completed trial had a particular probability of detecting an effect, and they do not change the uncertainty of the observed results. The registry record does not report that these assumptions were used to design the trial.
What cannot be inferred from the available analysis record? The record lists no analysis rows. It does not report an adjusted analysis, a formal unadjusted comparison, a model specification, or a multiplicity procedure. The record also says values were missing or not estimable for a two-arm comparison for another endpoint. That statement should not be extended to the primary outcome or to a specific secondary outcome unless identified in the record. Without the individual observations and analysis details, recalculating a valid comparative estimate is not possible from the posted arm medians and ranges alone.
In general, a p-value evaluates how unusual data at least as incompatible with a null hypothesis would be under the assumptions of a specified test. It does not measure the size or clinical importance of an effect. A confidence interval conveys estimation uncertainty and can help show which effect sizes remain compatible with the data and method. Neither is reported for the primary arm contrast in the registry record. The descriptive summaries should consequently be read without converting them into a claim of statistical significance or a claim that the arms are equivalent.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary HBI change outcome and secondary outcomes that include change in high-sensitivity C-reactive protein and safety and tolerability based on medication side effects and/or adverse events. It records four outcome measures overall. When several outcomes are assessed, there is a general risk that interpreting many separate tests without an appropriate plan can increase the chance of a chance finding. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical plan for interpreting multiple comparisons. No comparative p-values are posted for the primary outcome in the record.
The primary outcome description specifies that participants who withdraw for any reason before Day 15 will be considered treatment failures. That is a stated outcome-handling rule. However, the registry record does not report whether any withdrawals occurred, how many measurements were missing, whether participants were analyzed according to randomized assignment, or how the rule was implemented in the posted values. The analysis population is not reported in the registry record.
The registry record contains no posted analysis rows and notes that values were missing or not estimable for a two-arm comparison for another endpoint. The record does not identify that endpoint in this statement, so the limitation should not be attributed to a particular outcome. No imputation method, sensitivity analysis, or other missing-data procedure is reported. The arm summaries alone do not show how missing observations may have affected the results.
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 |
|---|---|---|---|
| Fluconazole | 0 | 4 | 0.0% |
| Placebo | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Fluconazole | 0 of 4 |
| Placebo | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Fluconazole | 4 of 4 |
| Placebo | 3 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Fluconazole | Placebo |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 4 of 4 | 2 of 4 |
| Increased diarrhea | Gastrointestinal disorders | 3 of 4 | 3 of 4 |
| Increased abdominal pain | Gastrointestinal disorders | 3 of 4 | 0 of 4 |
| Vomiting | Gastrointestinal disorders | 1 of 4 | 0 of 4 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 4 | 0 of 4 |
| Constipation | Gastrointestinal disorders | 0 of 4 | 1 of 4 |
| Perianal irritation | Gastrointestinal disorders | 0 of 4 | 1 of 4 |
| Flushing | Skin and subcutaneous tissue disorders | 1 of 4 | 0 of 4 |
| Decreased appetite | Gastrointestinal disorders | 1 of 4 | 0 of 4 |
| Eye irritation | Eye disorders | 0 of 4 | 1 of 4 |
The serious adverse event figures are counts of participants at risk and counts affected, reported separately by arm. In the Fluconazole arm, 4 participants were at risk for serious adverse events and 0 were affected. In the Placebo arm, 4 participants were at risk and 0 were affected. The registry also reports 0 deaths in each arm and lists no top serious adverse event terms.
These are observations during the period covered by the registry’s safety reporting. The counts do not establish that the regimen is free of serious risks. With few participants and limited follow-up information in the record, an event that was not observed in this trial could still occur in a larger or longer study. The registry record does not provide the exposure duration for the safety summaries or detailed information about event definitions and adjudication.
The record separately reports other adverse events: 4 participants were affected in the Fluconazole arm and 3 in the Placebo arm, with 4 at risk in each arm. These counts should not be confused with serious adverse events. The secondary outcome description refers to safety and tolerability based on medication side effects and/or adverse events, but the record does not provide enough detail to interpret the type, severity, timing, or relationship of the other events to treatment.
12. What the Result Does, and Does Not, Mean
The posted primary results show negative median changes in HBI score in both arms between enrollment and Day 15. The median change was -5.0 in the Fluconazole arm and -3.0 in the Placebo arm. The full ranges were -7.0 to 0.0 and -8.0 to -2.0, respectively. These summaries describe what was observed among the participants represented in the registry’s arm results; they are not a formal estimate of the effect attributable to fluconazole.
The posted information does not establish whether the apparent difference in arm medians is due to treatment, random variation, or other factors. No confidence interval or formal between-arm test is reported for the primary outcome. The small arm-level counts and the absence of individual participant values limit assessment of the distribution of responses. The registry record also does not state how missing data were handled in practice.
The result does not establish whether participants met remission or severe-disease thresholds at Day 15. The HBI thresholds in the outcome description refer to score levels, while the posted arm summaries are changes from baseline. The record does not provide counts by threshold or the corresponding baseline and Day 15 score distributions.
Nor do the primary results establish effects on high-sensitivity C-reactive protein, longer-term disease activity, or safety beyond the adverse-event counts recorded. The registry lists secondary outcomes, but complete comparative findings for them are not reported in the record details available for this analysis. A completed trial record and an observed change in a clinical score should not be read as proof of a treatment effect or as a basis for individual treatment decisions.
The appropriate statistical reading is narrow: the record reports descriptive short-term HBI changes in both randomized arms, with broad observed ranges relative to the small number of participants per arm. Further conclusions about the comparative effect require inferential analyses and outcome details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it illustrates the difference between an observed change within each arm and an estimated difference between arms. The posted medians describe change over time in each group. They do not, by themselves, quantify the causal contrast associated with assignment to fluconazole rather than placebo. Randomization supports a between-arm comparison in principle, but the record does not post the statistical comparison needed to interpret that contrast with quantified uncertainty.
The summaries also illustrate why a median should be read alongside the spread and the amount of information supporting it. The registry reports a full range, making clear that individual changes were not identical within either arm. At the same time, a range is not an uncertainty interval, and a median is not a substitute for participant-level data. Without the individual outcomes, it is not possible to evaluate the shape of the distributions or to reproduce an inferential analysis from the summaries.
The record’s statement about withdrawals is another important design-to-analysis issue. A protocol rule that treats withdrawal before Day 15 as treatment failure can affect how the primary endpoint is defined and analyzed. The registry record does not report whether withdrawals occurred or how this rule was applied. Statistical interpretation therefore depends not only on the summary values, but also on analysis details that are unavailable in the record.
Finally, the posted serious adverse event counts are zero in both arms, but a small trial cannot provide broad assurance about uncommon or delayed harms. The safety counts are useful as a report of observed events, not as proof that no serious risk exists. Taken together, these features make the study a useful example of how registry results can inform descriptive understanding while leaving comparative precision, missing-data handling, and generalizability unresolved.
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 outcome summaries come from a small study, with 4 participants reported in each arm. As a result, each observation can materially influence the median and full range. The results provide limited information about the variety of disease presentations or treatment responses that might occur beyond the enrolled group. The registry’s enrollment figure is 8, but the primary outcome entry does not give a more detailed account of the population contributing to the posted endpoint values.
The primary assessment is at Day 15, a short interval for evaluating a chronic disease. The posted endpoint does not establish persistence of change over longer follow-up. The registry record does not report later HBI results in the registry record for this analysis, nor does it provide enough detail to assess longer-term outcomes.
The intervention is a combined regimen that includes antibiotics and bowel lavage in both arms, with fluconazole or fluconazole placebo as the distinguishing component in the arm descriptions. Consequently, the primary contrast is not a comparison of the entire regimen against usual care or against no intervention. The record does not give enough detail to separate the contribution of the shared regimen from other influences on the observed changes.
The registry record does not report the detailed eligibility criteria, baseline participant characteristics, allocation implementation, analysis population, or the statistical plan. The primary endpoint description states a withdrawal rule, but the record does not say whether the rule was relevant to any participant or how missing measurements were handled. No formal comparative estimate or uncertainty interval is posted for the primary endpoint. These reporting gaps limit assessment of precision, balance between arms, and robustness of the results.
The safety record reports no serious adverse events or deaths in either arm, but the small amount of safety information and the absence of detailed timing and exposure information limit what can be concluded. The registry’s completed status does not resolve these limitations. The results are most appropriately interpreted as short-term descriptive observations from this trial.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease — NCT02765256.
- Registry record last updated 2024-02-06; status last verified 2024-02.
- Results first posted 2021-02-08.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes NCT02765256, a completed randomized, quadruple-masked, parallel-group phase 2 trial sponsored by the University of Pennsylvania. It enrolled 8 participants and studied a bowel lavage and antibiotic regimen with fluconazole or fluconazole placebo in people with active Crohn’s disease described as refractory to conventional immunosuppressive therapy.
The primary endpoint was change in HBI score between the enrollment visit and Day 15. The posted median change was -5.0, with a full range of -7.0 to 0.0, in the Fluconazole arm, and -3.0, with a full range of -8.0 to -2.0, in the Placebo arm. No formal between-arm analysis is reported in the registry record.
The registry lists change in high-sensitivity C-reactive protein and safety and tolerability as secondary outcomes. It reports 0 serious adverse events and 0 deaths in each arm. Missing-data handling, the analysis population, and a detailed statistical plan are not reported in the registry record.