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 FMT in Cirrhosis and Hepatic Encephalopathy (NCT03796598), a randomized phase 1, phase 2 study. The primary outcome is Serious Adverse Events Related to FMT.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03796598 |
| Phase | Phase 1, Phase 2 |
| Condition | Cirrhosis, Hepatic Encephalopathy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 60 |
| Arms in the primary outcome | 4 |
| Lead sponsor | VA Office of Research and Development |
| Results posted | Yes |
2. Clinical Question
Population
Veterans with cirrhosis and hepatic encephalopathy were the population of interest. The registry describes hepatic encephalopathy as confusion associated with advanced liver disease, and says the trial followed participants for safety and HE-related outcomes over 6 months.
Intervention
The intervention strategies used fecal microbiota transplant (FMT) by oral and/or rectal routes. The record describes a dual oral-and-rectal FMT group, an oral FMT with rectal placebo group, and an oral placebo with rectal FMT group. The described dosing included treatment at visit 2 and oral treatment at day 30.
Comparator
The comparator was placebo. Its description specifies oral and rectal placebo at visit 2 and oral placebo at day 30. The trial was randomized, quadruple-masked, and parallel-group.
Primary question
The primary endpoint counted participants with serious adverse events related to FMT, especially events related to HE, between groups over 6 months. The central statistical question is how the recorded counts compare across the placebo and FMT-route groups, and how much precision the posted results offer for those comparisons.
3. Trial Design
The registry identifies NCT03796598 as a randomized, quadruple-masked, parallel-group Phase 1/Phase 2 trial. It lists an enrollment of 60 and a completed status. The sponsor was the VA Office of Research and Development. The record gives a start date of 2019-07-29 and a primary completion date of 2023-12-19.
Four groups are described: placebo; oral placebo with rectal FMT; oral FMT with rectal placebo; and dual oral and rectal FMT. The placebo description specifies oral and rectal placebo at visit 2 and oral placebo at day 30. The FMT descriptions specify the corresponding route or routes at visit 2 and oral treatment at day 30. The posted primary safety outcomes list 15 participants in each group.
The primary outcome timeframe was 6 months. The record also lists secondary outcomes involving microbial diversity in stool and saliva, sickness impact, HE-related cognitive measures, and HE-related events. Some posted secondary outcome timeframes are 6 months and some are 60 days. The registry record does not report further details about the masking procedures, allocation sequence, stratification, or intended analysis populations.
The trial’s stated context is that HE can involve recurring episodes of confusion and related hospital admissions. The investigators proposed evaluating FMT delivered by upper and lower routes against placebo, with safety and HE-related outcomes as areas of follow-up. This description gives the trial’s rationale and scope, but does not establish efficacy or justify conclusions beyond the posted outcomes.
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 | Placebo | Group 3: Oral Placebo and Rectal FMT | Group 2: Oral FMT and Rectal Placebo | Group 1: Dual Oral and Rectal FMT |
|---|---|---|---|---|
| STARTED | 15 | 15 | 15 | 15 |
| COMPLETED | 15 | 15 | 15 | 15 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: number of patients
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: Patients with cirrhosis and hepatic encephalopathy
| Characteristic | Unit | Placebo | Group 3: Oral Placebo and Rectal FMT | Group 2: Oral FMT and Rectal Placebo | Group 1: Dual Oral and Rectal FMT | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 15 | 15 | 15 | 15 | 60 | |
| Age, Continuous | years | 63.4 (SD 7.5) | 60.6 (SD 10.3) | 63.0 (SD 11.7) | 65.0 (SD 7.1) | 63.0 (SD 9.2) |
| Sex: Female, Male: Female | Participants | 3 | 1 | 3 | 5 | 12 |
| Sex: Female, Male: Male | Participants | 12 | 14 | 12 | 10 | 48 |
| Race and Ethnicity Not Collected | Participants | — | — | — | — | 0 |
| Region of Enrollment: United States | Participants | 15 | 15 | 15 | 15 | 60 |
6. Primary Endpoint
The registry lists the primary outcome as Serious Adverse Events Related to FMT, measured over 6 months.
| 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 serious adverse events related to FMT during 6 months. The registry’s description emphasizes serious events between groups, particularly those related to HE. This is a participant count, not a measure of the number of separate events each person experienced.
A safety endpoint of this kind is used to describe whether serious harms considered related to the intervention were recorded during follow-up. Comparing the counts across randomized groups can provide a structured view of the recorded safety experience. The endpoint is not a general measure of all illness or all serious adverse events: its stated focus is serious adverse events related to FMT.
In the posted primary results, each group has a value of 0.0 for this outcome. The pairwise risk-difference estimates against placebo are also 0.0, with limits of 0.0 and 0.0. These registry figures describe the recorded primary outcome; they do not establish that the true risk is zero or resolve the interpretation of all serious events reported elsewhere in the safety data. The record does not report additional detail on how relatedness was adjudicated.
7. Results Posted in the Registry
- Group 3: Oral Placebo and Rectal FMT: 0.0% (0/15) versus 0.0% (0/15) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
- Group 2: Oral FMT and Rectal Placebo: 0.0% (0/15) versus 0.0% (0/15) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
- Group 1: Dual Oral and Rectal FMT: 0.0% (0/15) versus 0.0% (0/15) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
Risk difference: Group 3: Oral Placebo and Rectal FMT
95% CI: 0.0 to 0.0 percentage points
Recalculated from the posted summary statistics
8. Secondary Efficacy Endpoints
The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.
| Secondary outcome | Type | Effect measure | Estimate (95% CI) | Planning size, 80% power |
|---|---|---|---|---|
| Change in Microbial Diversity in Stool | Continuous Endpoint | Mean difference | 0.01 (-0.24 to 0.26) | 19,374 per arm |
| Change in Microbial Diversity in Saliva | Continuous Endpoint | Mean difference | 0.02 (-0.43 to 0.47) | 13,157 per arm |
| HE Related Events | Binary Endpoint | Risk difference | -40.0 pts (-64.8 to -15.2) | n/a |
Change in Microbial Diversity in Stool
- Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
- Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
- Result:
- Group 3: Oral Placebo and Rectal FMT: mean 1.46 versus 1.45 on control; difference 0.01 (95% CI -0.24 to 0.26), standardized effect d = 0.03; z-test p = 0.939.
- Group 2: Oral FMT and Rectal Placebo: mean 1.71 versus 1.45 on control; difference 0.26 (95% CI 0.01 to 0.51), standardized effect d = 0.74; z-test p = 0.046.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 3: Oral Placebo and Rectal FMT and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval excludes no difference, so the mean is statistically higher for Group 2: Oral FMT and Rectal Placebo than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
Change in Microbial Diversity in Saliva
- Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
- Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
- Result:
- Group 3: Oral Placebo and Rectal FMT: mean 1.57 versus 1.55 on control; difference 0.02 (95% CI -0.43 to 0.47), standardized effect d = 0.03; z-test p = 0.930.
- Group 2: Oral FMT and Rectal Placebo: mean 1.57 versus 1.55 on control; difference 0.02 (95% CI -0.25 to 0.29), standardized effect d = 0.06; z-test p = 0.885.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 3: Oral Placebo and Rectal FMT and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2: Oral FMT and Rectal Placebo and the control. The interval gives the range of effects that remain compatible with the data.
HE Related Events
- Endpoint type: Binary: the number of participants with the event, compared as proportions.
- Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
- Result:
- Group 3: Oral Placebo and Rectal FMT: 0.0% (0/15) versus 40.0% (6/15) on control; risk difference -40.0 percentage points (95% CI -64.8 to -15.2); unadjusted two-proportion z-test p = 0.006.
- Group 2: Oral FMT and Rectal Placebo: 13.3% (2/15) versus 40.0% (6/15) on control; risk difference -26.7 percentage points (95% CI -56.8 to 3.5), risk ratio 0.33 (0.08–1.39); unadjusted two-proportion z-test p = 0.099.
- Interpretation:
- The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Group 3: Oral Placebo and Rectal FMT than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2: Oral FMT and Rectal Placebo and the control. The interval gives the range of effects that remain compatible with the data.
The secondary outcomes span several domains rather than measuring a single underlying quantity. They include microbial diversity in stool and saliva, functional and cognitive measures, and HE-related events. The posted numeric results cover only a subset of the listed secondary outcomes. Results for sickness impact, Psychometric Hepatic Encephalopathy Score performance, and EncephalApp Stroop time are not reported in the registry record.
The recorded pattern is not uniform across domains. The stool-diversity comparisons differ in their estimated mean differences and unadjusted p-values; saliva values are close across the posted groups and both comparison intervals include zero. The HE-related-event counts are lower in each posted FMT group than in placebo, but the uncertainty differs between the two comparisons for which results are posted. These outcomes should not be collapsed into a single claim: biological diversity measures, clinical events, and cognitive or functional measures have different meanings.
The primary outcome concerns serious adverse events related to FMT, whereas secondary outcomes explore other safety, biological, and clinical questions. A secondary finding does not replace the primary endpoint, and it cannot by itself establish that the intervention caused a change in the primary safety outcome. Nor does a primary result of zero recorded related events establish that secondary outcomes are unchanged.
Unadjusted secondary results carry less weight when many outcomes and comparisons are considered because the chance of at least one apparently unusual result can increase across repeated testing. General explanation: multiplicity methods address that issue by changing how evidence is evaluated across a family of tests. The registry does not report a multiplicity adjustment or define a test family. Accordingly, individual unadjusted p-values should be treated as exploratory signals rather than as a single confirmatory conclusion. The statistical analysis plan, including any planned handling of multiple outcomes, is not reported in the registry record.
Secondary outcomes registered for this trial, for reference (only those above were recalculated):
- Adverse Events Related to FMT
- Change in Microbial Diversity in Stool
- Sickness Impact Profile Change
- Psychometric Hepatic Encephalopathy Score Performance Change
- EncephalApp Stroop Off and On Time Change
- Change in Microbial Diversity in Saliva
- HE Related Events
9. Statistical Interpretation
The primary outcome is a safety count: participants with serious adverse events related to FMT over 6 months. The posted value is 0.0 in the placebo group and in each of the three FMT-route groups. The registry’s pairwise risk-difference results against placebo are 0.0, with limits of 0.0 and 0.0. Thus, according to the recorded primary endpoint, no between-group difference was posted for this particular outcome.
This finding should be kept distinct from the broader serious-adverse-event listings. Those report serious adverse events affecting 6 participants in the placebo group, 5 in the oral-placebo/rectal-FMT group, 5 in the oral-FMT/rectal-placebo group, and 6 in the dual-route group. They also report deaths of 1, 0, 1, and 1, respectively. These overall safety counts are not the same measure as serious adverse events judged related to FMT. The registry’s most common serious-event terms include liver-related hospitalizations at 40.0%, infection at 20.0%, falls at 6.7%, and seizure recurrence at 6.7%.
The HE-related-event outcome is separate from the primary safety endpoint. The placebo group has 6 participants with HE-related events, while the rectal-FMT group has 0 and the oral-FMT and dual-route groups each have 2. The posted unadjusted comparison for rectal FMT versus placebo has p = 0.006. For oral FMT versus placebo, p = 0.099; its confidence interval includes zero. These are secondary results and should not be treated as definitive evidence of a causal benefit, particularly because the registry does not report a multiplicity adjustment or a complete analysis plan.
For microbial diversity in stool, posted group means at 6 months range from 1.45 to 1.71. The oral-FMT/rectal-placebo comparison has a mean difference of 0.26, with a confidence interval that does not include zero and an unadjusted p = 0.046. The other posted stool comparison has a mean difference of 0.01 and p = 0.939. For saliva diversity at 60 days, the posted group means range from 1.55 to 1.57, and the two posted comparisons have unadjusted p-values of 0.93 and 0.885. The registry does not list reported analyses for these outcomes.
These outcomes address different questions: serious FMT-related events concern safety, HE-related events concern clinical events, and microbial diversity concerns a biological measure. A pattern in one does not automatically explain or validate a pattern in another. The posted results describe this trial’s observed data; uncertainty, missing analysis details, and the narrow scope of each endpoint limit broader conclusions.
10. Statistical Methods Explained
Randomization assigns participants to groups by chance. In general, this design aims to make group comparisons less vulnerable to systematic differences present before treatment, although chance imbalances can still occur. The registry identifies the study as randomized and parallel-group, but the sequence-generation and allocation-concealment methods are not reported in the registry record.
Quadruple masking means the registry labels the study as masked at four levels, but the record does not specify which people or roles were masked or how masking was maintained. It would be inappropriate to infer those details from the label alone. Likewise, the posted record does not provide enough information to determine whether masking was successful.
What does a risk difference describe?
General explanation: a risk difference compares the proportion of participants with an outcome in one group with the proportion in another. A value of 0.0 indicates no observed difference in those proportions. Positive and negative values indicate which group had the larger observed proportion, according to the stated comparison order. The primary result’s posted risk differences are 0.0 for all three FMT groups versus placebo. For the secondary HE-related-event comparisons, the direction is expressed relative to placebo.
A participant count is not a rate per unit of follow-up time, and it does not tell how many events each participant experienced. The primary endpoint is explicitly a count of participants with serious FMT-related adverse events. The registry does not report a time-to-event analysis for this endpoint.
What does a mean difference describe?
General explanation: a mean difference subtracts one group’s average from another group’s average, using the comparison’s stated order. It is expressed in the outcome’s own units. For the microbial-diversity outcomes, the record reports means in units on a scale and standard deviations as measures of within-group spread. The posted stool comparison of oral FMT with rectal placebo versus placebo has a mean difference of 0.26. The posted stool comparison of rectal FMT versus placebo has a mean difference of 0.01. The saliva mean differences are 0.02 for each of the two posted comparisons.
A standard deviation describes how spread out individual measurements are around a group mean; it is not the same as uncertainty in the mean. The record reports standard deviations for the diversity outcomes. It does not report group-level confidence intervals for those means.
How should p-values be read?
General explanation: a p-value describes how compatible data are with a specified null model, under the assumptions of the test. It does not give the probability that the null hypothesis is true, measure the size or importance of an effect, or establish causation. The posted p-values for secondary outcomes are described as unadjusted. The registry record does not list reported analyses or explain the tests used, so the exact analysis procedures behind these values are not reported in the registry record.
The unadjusted p-value for the stool oral-FMT comparison is 0.046. The posted p-values for the other stool comparison and both saliva comparisons are 0.939, 0.93, and 0.885. For HE-related events, the posted p-values are 0.006 for rectal FMT versus placebo and 0.099 for oral FMT versus placebo. These values should be read alongside their estimates and confidence intervals, not in isolation.
Why does over-dispersion matter?
General explanation: over-dispersion arises when variation in count data is greater than a chosen statistical model expects. If a model assumes less variability than the data contain, it can understate uncertainty and make results appear more precise than warranted. The registry reports participant counts for the binary outcomes and does not report a count-model analysis or an over-dispersion assessment. This issue is therefore a general consideration, not a finding established for this trial.
What are the sample-size illustrations?
The planning illustrations are based on observed effects and are not the trial’s design justification or observed power. For planning based on microbial diversity in stool, the posted figures range from 19,374 to 77,496 participants per arm for 80% power for the rectal-FMT comparison, and from 29 to 115 participants per arm for the oral-FMT comparison. For saliva diversity, the corresponding figures range from 13,157 to 52,627 and from 4,804 to 19,215 participants per arm. For the oral-FMT comparison on HE-related events, the figures range from 42 to 196 participants per arm. These illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; they use the stated fraction of the observed effect. They do not show that the completed trial had a particular power, and the registry’s own sample-size justification is not reported in the registry record.
11. Confidence Intervals and Precision
A confidence interval describes a range of values compatible with the data and the method used to calculate it. General explanation: narrower intervals indicate greater precision under that method, while wider intervals indicate greater uncertainty. An interval crossing zero for a difference includes values in both directions as well as no difference; it does not prove that the groups are identical.
For the primary FMT-related serious-adverse-event outcome, each posted pairwise risk difference is 0.0 and its limits are 0.0 and 0.0. The displayed result is therefore numerically at a single value. However, the outcome was recorded as 0.0 in all four groups. Such a result offers little observed separation between groups for estimating a difference in this dataset; it should not be read as proof that the true risks are exactly equal or absent.
The HE-related-event comparison for rectal FMT versus placebo has a posted risk difference of -0.4 and an interval that does not include zero. The oral-FMT comparison has a posted risk difference of -0.267 and an interval that includes zero. The intervals convey uncertainty around the observed differences; their interpretation remains limited by the small group counts and by the lack of a reported analysis plan and multiplicity approach.
For stool diversity, the rectal-FMT comparison’s interval includes zero, while the oral-FMT comparison’s interval excludes zero. For saliva diversity, both posted intervals include zero. The posted analyses are unadjusted, and the registry does not list reported analyses. These confidence intervals therefore describe the individual comparisons as posted, not a joint assessment across the many outcomes.
12. Multiplicity, Missing Data and Analysis Populations
The registry lists 8 outcome measures and 7 posted secondary outcomes, but it does not provide a complete set of results for every listed secondary measure. The numeric results include microbial diversity in stool and saliva and HE-related events. Results for the other listed secondary measures are not reported in the registry record. The record also lists 0 reported analyses, so it does not give a formal account of the analysis methods used for these outcomes.
The posted secondary comparisons have unadjusted p-values. Whether the investigators planned a hierarchy of outcomes, a multiplicity correction, or another approach to control interpretation across repeated tests is not reported in the registry record. General explanation: when many hypotheses are tested, an isolated small p-value may arise by chance more often than in a single prespecified test. Without the planned testing framework, the values should be understood as individual unadjusted comparisons rather than as a controlled family of confirmatory tests.
The registry gives analyzed group counts for several outcomes, and those counts are not identical across all secondary measures. It does not explain why the counts differ, how missing outcome data were handled, or whether any participants were excluded from particular analyses. Missing-data methods, imputation, and sensitivity analyses are not reported in the registry record.
The analysis population is also not reported in the registry record. The record does not say whether analyses followed an intention-to-treat, per-protocol, or other population definition. It also does not report a detailed statistical analysis plan, covariate adjustment, interim analyses, or a sample-size justification. These omissions make it difficult to assess whether the posted comparisons follow prespecified methods, how incomplete observations might affect estimates, and how the secondary findings were intended to be interpreted.
13. 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 |
|---|---|---|---|
| Placebo | 6 | 15 | 40.0% |
| Group 3: Oral Placebo and Rectal FMT | 5 | 15 | 33.3% |
| Group 2: Oral FMT and Rectal Placebo | 5 | 15 | 33.3% |
| Group 1: Dual Oral and Rectal FMT | 6 | 15 | 40.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 1 of 15 |
| Group 3: Oral Placebo and Rectal FMT | 0 of 15 |
| Group 2: Oral FMT and Rectal Placebo | 1 of 15 |
| Group 1: Dual Oral and Rectal FMT | 1 of 15 |
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 |
|---|---|
| Placebo | 0 of 15 |
| Group 3: Oral Placebo and Rectal FMT | 0 of 15 |
| Group 2: Oral FMT and Rectal Placebo | 0 of 15 |
| Group 1: Dual Oral and Rectal FMT | 0 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Group 3: Oral Placebo and Rectal FMT | Group 2: Oral FMT and Rectal Placebo | Group 1: Dual Oral and Rectal FMT |
|---|---|---|---|---|---|
| Liver-related hospitalizations | Hepatobiliary disorders | 6 of 15 | 2 of 15 | 2 of 15 | 2 of 15 |
| Infection | Infections and infestations | 3 of 15 | 2 of 15 | 2 of 15 | 3 of 15 |
| Falls | Musculoskeletal and connective tissue disorders | 1 of 15 | 0 of 15 | 1 of 15 | 1 of 15 |
| Seizure recurrence | Nervous system disorders | 0 of 15 | 1 of 15 | 0 of 15 | 0 of 15 |
Serious events with the highest arm-level rate: liver-related hospitalizations (40.0%), infection (20.0%), falls (6.7%), seizure recurrence (6.7%).
The primary safety endpoint counts participants with serious adverse events related to FMT. The posted value is 0.0 in each group, and the posted risk differences versus placebo are 0.0. These figures refer to the endpoint’s relatedness definition, not to every serious adverse event recorded during the trial.
The broader safety listing reports serious adverse events in 6 participants in placebo, 5 in oral placebo with rectal FMT, 5 in oral FMT with rectal placebo, and 6 in dual oral and rectal FMT. Deaths are recorded as 1, 0, 1, and 1 in those same groups. The listed serious-event terms include liver-related hospitalizations, infection, falls, and seizure recurrence. These data should be read separately from the primary related-event count because they describe the overall serious-event listings rather than only events classified as FMT-related.
The registry record does not provide individual event narratives, severity detail beyond the serious-event designation, or the process for determining relatedness. These counts describe events recorded in the registry; they are not a complete assessment of every potential safety question.
14. What the Result Does, and Does Not, Mean
The posted results describe what was recorded for this randomized trial. For the primary endpoint, the registry reports 0.0 participants with serious adverse events related to FMT in each group over 6 months. That is a statement about the observed primary outcome and its recorded classification, not proof that the true risk is zero or that all serious events were unrelated to FMT.
The overall serious-adverse-event counts and deaths show that serious events were recorded in the groups, even though the primary related-event count is zero. The distinction matters: one result concerns events judged related to FMT, while the broader safety listing concerns serious events without the same stated restriction. The registry record does not explain the event-level relationship between these two listings.
Secondary outcomes provide additional, but not definitive, information. HE-related-event counts and microbial-diversity values differ across some groups, while other comparisons show little separation in the posted means. Their unadjusted analyses, incomplete reporting across listed outcomes, and missing details about the statistical plan limit how strongly any single secondary comparison can be interpreted.
These results do not establish that FMT improves HE, changes daily functioning, or reduces hospitalization. They also do not establish equivalence between treatment strategies or rule out harms that were not captured by this endpoint or follow-up. The record does not report the analysis population, missing-data methods, multiplicity approach, or detailed adjudication procedures. Interpretation should therefore remain tied to the specific outcomes, timeframes, and comparisons the registry reports.
15. Why This Trial Matters Statistically
This trial raises several statistical issues that are common in clinical research. First, a safety endpoint and a clinical-effect endpoint answer different questions. The primary measure counts serious adverse events classified as related to FMT, while HE-related events are a secondary clinical outcome. A zero result on the primary measure cannot be substituted for an estimate of clinical benefit or for a comprehensive account of safety.
Second, small group counts can produce sparse binary outcomes. When the primary endpoint is recorded as zero in every group, there is no observed difference to distinguish the groups on that measure. The posted risk differences and intervals are all 0.0, but this numerical result should not be mistaken for certainty about the underlying risks. Sparse data make the distinction between an observed count and the range of plausible underlying values especially important.
Third, the registry posts multiple secondary comparisons with unadjusted p-values. General explanation: examining many outcomes creates more opportunities for chance findings, so interpretation depends on whether comparisons were prespecified and how multiplicity was handled. Those details are not reported in the registry record. The diversity and HE-related results are therefore best viewed as separate exploratory observations rather than one unified conclusion.
Finally, the sample-size illustrations are based on observed effects, not on the trial’s design assumptions. Their large variation across outcomes shows why planning depends on the endpoint, variability, and effect targeted; they do not show the trial’s observed power. The trial record’s own sample-size justification and analysis plan are not reported. These distinctions are important when readers assess what the data can support and what remains uncertain.
16. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record has several limitations for interpreting this trial’s results. It does not report a full statistical analysis plan, the analysis population, the handling of missing data, or the methods used to calculate the posted comparisons. It also does not report whether the secondary outcomes were analyzed according to a prespecified hierarchy or whether any multiplicity adjustment was used.
Posted results cover only some of the listed secondary outcomes. Findings for sickness impact, Psychometric Hepatic Encephalopathy Score performance, and EncephalApp Stroop time are not reported in the registry record. The analyzed group counts vary across the secondary measures, but reasons for this variation and any exclusions are not reported in the registry record.
Safety interpretation is also limited by the distinction between the primary FMT-related serious-event endpoint and the broader serious-event counts. The registry does not provide event narratives, adjudication methods, or an explanation of the relationship between those listings. The primary outcome has zero recorded events in all groups, which limits the observed information for comparing groups on that endpoint.
The planning illustrations use observed effects and are not a substitute for the trial’s design justification. The registry does not report that justification, details of the randomization process, or which people were masked. It also does not provide individual participant data. These limits mean the posted summaries cannot resolve all questions about bias, missingness, precision, or how the analyses were planned.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: FMT in Cirrhosis and Hepatic Encephalopathy — NCT03796598.
- Registry record last updated 2025-05-25; status last verified 2025-05.
- Results first posted 2025-05-25.
- 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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20. Record Summary
NCT03796598, titled “FMT in Cirrhosis and Hepatic Encephalopathy,” is listed as a completed randomized, quadruple-masked, parallel-group Phase 1/Phase 2 trial sponsored by the VA Office of Research and Development. The registry lists enrollment of 60, a start date of 2019-07-29, and primary completion on 2023-12-19.
The trial compared placebo with oral, rectal, and dual-route FMT strategies in Veterans with cirrhosis and hepatic encephalopathy. Its primary outcome was participants with serious adverse events related to FMT over 6 months. The posted primary result is 0.0 in each group. Broader serious-event listings report events and deaths, while secondary results cover selected HE-related and microbial-diversity measures.
Important analysis details—including the analysis population, missing-data methods, multiplicity approach, and trial-specific sample-size justification—are not reported in the registry record. The posted results should be interpreted as registry outcome summaries rather than a complete account of the trial’s statistical analysis.