A Retrospective, Open-label, Uncontrolled Cohort Study to Assess the Effectiveness and Safety of Lactulose Retention Enema in the Treatment of Cirrhotic Patients With Grade 3 or 4 (West Haven Criteria) Hepatic Encephalopathy (HE) [The RETRO Study]: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Retrospective, Open-label, Uncontrolled Cohort Study to Assess the Effectiveness and Safety of Lactulose Retention Enema in the Treatment of Cirrhotic Patients With Grade 3 or 4 (West Haven Criteria) Hepatic Encephalopathy (HE) [The RETRO Study] (NCT02377947), a registered phase not stated study. The primary outcome is Complete Reversal.

2. Clinical Question

In statistical terms, the question concerns an observed outcome in a treated cohort, not a randomized contrast between treatments. Without a concurrent control group, the study can describe what was documented after treatment, but it cannot isolate the treatment’s contribution from other aspects of care, patient characteristics, or the course of the illness.

The registry also lists hepatic encephalopathy grade shift at 24 and 48 hours, time to complete reversal, and mortality as secondary outcomes. It reports 8 outcome measures overall, but does not provide the numerical results of those secondary outcomes in the record represented. The clinical question is therefore most directly addressed by a reported estimate of complete reversal at the stated time point, accompanied by its uncertainty. That estimate and interval are not reported in the registry record.

3. Trial Design

The RETRO Study is registered as a retrospective, open-label, uncontrolled cohort study. Its stated focus is the effectiveness and safety of lactulose retention enema in cirrhotic patients with Grade 3 or 4 hepatic encephalopathy according to the West Haven Criteria. The listed enrollment is 50. The registry status is COMPLETED, with study dates recorded as 2015-12 for start and 2016-03 for primary completion.

The study description says that hospital records from the past 6 months would be identified retrospectively at multispecialty tertiary care hospital centers in India. It characterizes lactulose retention enema as the mainstay of management at those centers and says the standard treatment protocol would be followed, including respecting known contraindications before administration. The described dose is 300ml of lactulose mixed with 700ml of potable water, retained for 30-60 minutes and repeated every 4-6 hours until the patient can take oral medication.

The listed arm contains patients with cirrhosis and Grade 3 or 4 hepatic encephalopathy who were treated with the enema. No separate untreated or alternative-treatment arm is described. The study is therefore not a randomized comparison, and the record does not state an allocation procedure. An uncontrolled cohort can describe outcomes observed among treated patients, but it does not provide a like-for-like control comparison that would account for what might have happened to similar patients under another care strategy.

The primary completion timeframe for the endpoint is 24 hrs. The registry lists grade shift at 24 and 48 hours, time to complete reversal, and mortality among the secondary outcomes. Details of the retrospective record-selection process, eligibility exclusions, follow-up completeness, and outcome adjudication 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

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 Complete Reversal, measured over 24 hrs.

The primary endpoint is the percentage of patients with complete reversal of deep-grade hepatic encephalopathy after administration of lactulose retention enema, assessed at 24 hrs. The eligible grades are Grade 3 and Grade 4 under the West Haven Criteria. The registry identifies the outcome as a percentage of participants and specifies a 95% Confidence Interval as its dispersion measure.

Complete reversal is an outcome expressed in terms of a clinical state rather than a change in a laboratory value. As a general statistical principle, a clearly defined patient-level outcome can be summarized by counting how many participants meet the outcome definition and relating that count to the group assessed. The resulting percentage gives an estimate of the frequency of the outcome in that cohort. A confidence interval communicates uncertainty around an estimate; it does not guarantee that the true value lies within the interval, and its width depends in part on the amount of information available and the observed pattern of outcomes.

The endpoint is relevant to the study’s stated aim because it asks whether patients reached complete reversal by the specified assessment time. However, the operational criteria for deciding that reversal was complete, the count meeting the endpoint, the percentage, and the interval are not reported in the registry record. The record therefore identifies what the primary endpoint was intended to measure, but does not allow readers to quantify the observed primary outcome or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary-style primary outcome: whether complete reversal of deep-grade hepatic encephalopathy was recorded at 24 hrs. It expresses the endpoint as a percentage of participants and names a 95% Confidence Interval as the measure of dispersion. The numerical endpoint result is not reported in the registry record, and the record lists 0 analyses. Thus, the statistical methods named for the endpoint can be explained in general, but the analysis actually used and its result cannot be verified from this record.

What does a percentage estimate?

For an outcome classified as either meeting or not meeting a definition, a percentage describes the fraction of assessed participants who met that definition. The estimate depends on having a defined denominator and a consistent rule for classifying the outcome. In this study, the stated denominator type is participants, but the record does not report how many participants were assessed for the primary endpoint or how many met it. The listed enrollment of 50 is not, by itself, confirmation that all 50 had an evaluable 24-hour assessment.

As a general statistical explanation, the percentage is an estimate of the outcome frequency in the cohort, not a direct estimate of a treatment effect against a comparator. A treatment effect in a comparative study is generally expressed through a contrast between groups. The RETRO Study is described as uncontrolled, so there is no registered comparator-group outcome against which to form that contrast.

What does the confidence interval convey?

A confidence interval expresses uncertainty around an estimated quantity under the assumptions of the method used to construct it. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The interval does not correct problems in study design, measurement, selection, or missing data. It also does not show that a treatment caused the outcome. The registry specifies a 95% Confidence Interval for the primary outcome but does not report its endpoints, the method used to calculate it, or the underlying event count.

For a binary outcome, methods commonly account for the fact that an observed participant either meets the outcome definition or does not. Different interval methods can behave differently, particularly when event counts are limited or close to the boundaries of the possible range. This is a general methodological point; the registry record does not state which interval method was used, so no method-specific properties can be attributed to this analysis.

Why does the uncontrolled design constrain inference?

Statistical uncertainty and causal uncertainty are distinct. A confidence interval can describe uncertainty around a cohort estimate, but it cannot create a control group that the design did not include. In a retrospective uncontrolled study, changes observed after treatment may also reflect patient characteristics, concurrent care, clinical course, or the way outcomes were recorded. Statistical adjustment can sometimes address measured differences in comparative data, but the registry does not report a comparative analysis or an adjustment plan.

The study is open-label, and the outcomes rely on clinical classifications and hospital records. In general, open-label assessment may allow knowledge of treatment to influence measurement or documentation. Retrospective record review also depends on the availability and consistency of recorded information. The registry does not describe whether outcome assessors were blinded, whether a standard review procedure was used, or how incomplete or ambiguous entries were handled.

How should the planning illustrations be read?

The registry’s planning assumptions describe illustrations computed from an observed effect, rather than the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event calculations, the assumptions refer to the total number of events, while other calculations refer to participants per arm.

These are planning conventions, not evidence that the study randomized participants or included two arms. The registered study is uncontrolled. Planning illustrations based on an observed effect are not observed power, and they do not establish that the trial had a particular probability of detecting an effect. The numerical planning outputs are not reported in the registry record used for this description. The record also does not report the trial’s own sample-size justification or a formal power calculation.

What analysis details remain unknown?

The registry lists 0 analyses. It does not report a named statistical test, an interval-construction method, covariate adjustment, a method for handling repeated assessments, or rules for analyzing incomplete records. The record lists multiple outcome measures, but it does not report how they were prioritized or whether any adjustment for multiple comparisons was planned. These absences prevent a detailed reconstruction of the analysis and should not be filled by assuming that a particular standard method was used.

In general, analysis methods should follow the outcome type, study design, and data structure. A binary endpoint, a time-to-event outcome, and repeated clinical grades raise different analytic questions. Appropriate methods depend on definitions, timing, available observations, and assumptions. Since those details and the numerical results are not reported in the registry record, the defensible interpretation is limited to the stated endpoint, cohort design, and listed outcomes.

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("Patients With Cirrhosis (Grade 3 & 4 Per West Have")
n      <- c(50)
events <- c(40)
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  Patients With Cirrhosis (Grade 3 & 4 Per West Have  50  40  80.0  66.3  90.0  67.0  88.8  66.9  88.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the primary complete-reversal endpoint and secondary outcomes for hepatic encephalopathy grade shift at 24 and 48 hours, time to complete reversal, and mortality. It reports 0 analyses. A list of several outcomes raises a general multiplicity question: when multiple outcomes are examined, the chance of finding at least one seemingly notable result can differ from the chance associated with a single prespecified test. The registry does not report a multiplicity strategy, such as prioritizing a limited set of confirmatory comparisons or adjusting inference across outcomes.

The record identifies a primary endpoint, which communicates the principal outcome of interest, but does not report the analysis plan or whether the distinction between primary and secondary outcomes was used to govern interpretation. The numerical results for the listed outcomes are not reported in the registry record, so their relative findings and any relationship among them cannot be assessed.

Missing-data handling is also not reported in the registry record. The enrollment is 50, but the record does not state how many participants had each assessment, whether any records were incomplete, how missing outcome values were handled, or whether the analysis used all enrolled participants or a subset. The analysis population and any exclusions from outcome calculations are not reported in the registry record. These details matter because the denominator used for an outcome can differ from total enrollment, and the reason data are absent can affect how an estimate should be interpreted.

The record does not report an imputation method, a sensitivity analysis for missing data, or a plan for assessing whether missingness was related to clinical status. No assumptions about these procedures can be inferred from the retrospective design or from the completed status. As a general principle, readers need the outcome-specific denominator and a transparent account of missing observations to judge how representative a percentage may be.

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 non-serious adverse event terms

The safety information lists 50 participants at risk for serious adverse events and 0 affected. It also lists 50 at risk in the other adverse-event category and 3 affected. Deaths are listed as 6. These are counts in the registry record; no percentages are calculated.

The absence of recorded serious adverse events among the listed participants is not proof that no serious events occurred outside the captured records, nor does it establish that the risk is absent. The registry does not provide serious adverse event terms, and no top serious terms are listed. Details for the 3 participants in the other adverse-event category are not reported in the registry record.

The record does not explain whether the deaths overlap with the adverse-event counts, when they occurred, or whether they were considered related to treatment. The deaths should therefore be read as a separate reported count, not assumed to be treatment-related or unrelated. No comparison group is available in the registered design, so these figures do not establish how safety outcomes compare with another care strategy. As a general principle, safety counts require context about event definitions, follow-up, attribution, and completeness of reporting before causal conclusions can be considered.

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

The registry record establishes that the RETRO Study examined a retrospective cohort of cirrhotic patients with Grade 3 or 4 hepatic encephalopathy treated with lactulose retention enema. It identifies complete reversal at 24 hrs as the primary endpoint and specifies that the outcome was to be expressed as a percentage with a 95% Confidence Interval. It does not report the primary endpoint result. The record therefore does not show how many participants achieved complete reversal or how precisely that outcome was estimated.

The record also describes an uncontrolled design. Any outcomes observed in the treated cohort would be descriptive of that cohort and its recorded care. Without a comparison group, the study cannot show what would have occurred in comparable patients under another approach. This limitation remains even if an outcome estimate is precise, because precision around a cohort description does not resolve causal uncertainty.

The listed secondary outcomes indicate additional questions of interest, including grade shift, time to complete reversal, and mortality. Their names alone do not provide evidence about the direction, size, or certainty of any observed result. The record reports 0 analyses, and numerical results for those outcomes are not reported in the registry record.

The safety fields list 0 serious adverse event participants among 50 at risk, 3 participants affected in the other adverse-event category among 50 at risk, and 6 deaths. These counts do not specify event details, timing, overlap, or causal attribution. They should not be interpreted as comparative risks or as proof that treatment caused or did not cause an event.

In general, a registry entry is most informative when its outcome definitions, denominators, methods, and results can be considered together. Here, the design and intended outcomes are described, but key numerical efficacy results and analysis details are absent. Accordingly, the record supports a description of what the study set out to examine and of the safety counts it lists, but it does not support a quantified conclusion about the primary endpoint or a causal treatment comparison.

14. Why This Trial Matters Statistically

This study is statistically instructive because it makes the distinction between describing an outcome and estimating a treatment effect especially clear. The RETRO Study is a retrospective, open-label, uncontrolled cohort study. Its primary endpoint asks what percentage of treated patients had complete reversal of deep-grade hepatic encephalopathy at 24 hrs. That is a meaningful descriptive question, but without a control group it is not a direct comparison of treatment strategies.

The registry identifies a 95% Confidence Interval for the primary endpoint, drawing attention to estimation precision. In general, intervals help readers judge how much uncertainty accompanies a point estimate. Yet an interval addresses only uncertainty under the chosen statistical method and data structure; it cannot remove the design’s lack of a comparator, correct undocumented outcome assessment, or establish a causal relationship. In this record, the interval and point estimate are not reported, so even the descriptive precision cannot be judged.

The retrospective setting also illustrates the importance of data provenance. The study relies on hospital records, and the registry does not describe completeness, assessment procedures, or missing-data handling. These are not minor reporting details: they determine what participants and outcomes are represented in an analysis and how reliably the outcome can be classified.

The safety information offers another useful interpretive lesson. Counts of serious events, other adverse events, and deaths are not self-interpreting. Event definitions, timing, overlap, attribution, and follow-up affect what a count means. The registry’s numerical safety fields can be reported as counts, but they do not establish causation or comparative safety.

Finally, the planning assumptions distinguish hypothetical sample-size illustrations from the trial’s actual design. Their stated two-arm allocation assumptions do not turn an uncontrolled cohort into a comparative study. Keeping those concepts separate prevents planning calculations from being mistaken for observed evidence or for a design feature that the registry does not describe.

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 main trial-specific limitation is the absence of a comparator group. The registry explicitly describes an uncontrolled cohort, so outcomes among treated patients cannot be contrasted with outcomes among a comparable group receiving another strategy. The record also does not state an allocation method. It therefore does not support a randomized treatment-effect interpretation.

Retrospective data collection depends on the content and quality of hospital records. The registry says records from the past 6 months would be identified, but does not report how records were selected, whether all eligible records were available, how incomplete records were handled, or whether outcome assessments were standardized. The operational definition of complete reversal is not reported in the registry record. The process for confirming hepatic encephalopathy grade or resolving uncertain classifications is also not reported.

The study is open-label, and the registry does not report blinded outcome assessment. It does not describe concurrent treatments or how differences in care were handled analytically. The record does not report the primary endpoint count, percentage, confidence interval, or secondary outcome results. Although enrollment is 50, outcome-specific denominators and the analysis population are not reported in the registry record.

Statistical details are sparse. The registry lists 0 analyses and does not report the analysis methods, a missing-data approach, or a multiplicity plan. It also does not report the trial’s own sample-size justification or whether interim analyses were planned. The safety fields do not specify event descriptions, timing, overlap, or attribution of deaths. These limitations restrict both the reproducibility of the analysis and the strength of conclusions that can be drawn from the registry entry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Retrospective, Open-label, Uncontrolled Cohort Study to Assess the Effectiveness and Safety of Lactulose Retention Enema in the Treatment of Cirrhotic Patients With Grade 3 or 4 (West Haven Criteria) Hepatic Encephalopathy (HE) [The RETRO Study] — NCT02377947.
• Registry record last updated 2020-02-10; status last verified 2020-02.
• Results first posted 2020-02-10.
• 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

The RETRO Study is registered as a completed, retrospective, open-label, uncontrolled cohort study of lactulose retention enema in cirrhotic patients with Grade 3 or 4 hepatic encephalopathy under the West Haven Criteria. Enrollment is 50. The listed primary endpoint is the percentage of participants with complete reversal at 24 hrs, with a 95% Confidence Interval specified. The endpoint result and interval are not reported in the registry record.

The registry lists 8 outcome measures and 0 analyses. Secondary outcomes include hepatic encephalopathy grade shift at 24 and 48 hours, time to complete reversal, and mortality. Safety fields list 0 serious adverse event participants among 50 at risk, 3 participants affected in the other adverse-event category among 50 at risk, and 6 deaths. Event details and attribution are not reported in the registry record. The uncontrolled design supports descriptive interpretation only and does not provide a like-for-like control comparison.