Reversal of Hepatic Impairment in Patients With Hepatitis C Virus (HCV) and Early Decompensation of Cirrhosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reversal of Hepatic Impairment in Patients With Hepatitis C Virus (HCV) and Early Decompensation of Cirrhosis (NCT02455167), a na phase 3 study. The primary outcome is The Sustained Virologic Response (SVR) in Patients Infected With HCV Genotype 1, Cirrhosis, and Early Clinical Decompensation.

2. Clinical Question

3. Trial Design

The registry identifies NCT02455167 as a phase 3, single-group study sponsored by the University of Colorado, Denver. Its title concerns reversal of hepatic impairment in people with HCV and early decompensation of cirrhosis. The official title specifies HCV genotype 1 infection and MELD 10 or less. The record lists enrollment as 9 and gives the study status as terminated. The recorded start is 2015-05, and the primary completion date is 2016-07-18. The reason for termination is not reported in the registry record.

The intervention was the combination of simeprevir, sofosbuvir and ribavirin. The brief summary describes a 12-week course and identifies two aims: achieving sustained virologic response and evaluating hepatic improvement during and after treatment with HepQuant-SHUNT. The primary outcome measure concerns sustained virologic response at 12 weeks. The record lists 3 outcome measures, but further details about the other measures are not reported in the registry record.

Allocation is listed as not applicable, the model is single group, and masking is listed as none. These features mean the study does not include a randomized, masked, concurrent comparison arm. Its design can describe outcomes observed in the treated group if those outcomes are reported, but cannot by itself estimate a contrast against an untreated group or another regimen. The registry record does not report a protocol-level rationale for the design or a sample-size justification.

The record reports no analyses. In particular, it does not give a primary endpoint count, analysis population, or statistical estimate comparing groups. Since there is no comparison group, comparative treatment effects are not part of the design described. The enrollment figure should not be assumed to be the denominator for the primary outcome: the number assessed for that endpoint is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 5 participants screen-failed after enrollment.

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 The Sustained Virologic Response (SVR) in Patients Infected With HCV Genotype 1, Cirrhosis, and Early Clinical Decompensation, measured over 12 weeks.

The primary endpoint is the number of participants whose HCV RNA was “Not Detected” after 12 weeks. In the registry description, that finding defines clearance of HCV for the sustained virologic response outcome. The endpoint is recorded as a participant count, rather than as a continuous laboratory value or a comparison between study arms. It focuses on virologic status at the specified assessment time.

In general, a virologic response endpoint is used to describe whether the virus is detectable after treatment, which gives a direct, clinically interpretable measure of the intended antiviral outcome. A count can convey how many participants met the defined criterion, but its interpretation depends on the number assessed and on how missing or unevaluable results are handled. Those details are not reported in the registry record. Nor does the record report the observed count meeting the endpoint, so the posted information does not establish the response proportion or its precision.

The study’s broader aim also included hepatic improvement measured with HepQuant-SHUNT. That aim is distinct from the primary virologic endpoint: an HCV RNA result does not itself quantify liver function. The registry description does not report the HepQuant-SHUNT outcome results or explain how hepatic improvement was defined. The virologic endpoint can therefore be described from the record, while conclusions about observed hepatic change cannot be drawn from the information available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a count outcome in a single-group study. That distinction matters when interpreting statistical methods: a count can be reported directly, but a treatment comparison requires a suitable contrast, and this design does not include a concurrent comparison group. No analysis methods are reported in the registry record, so the explanation below distinguishes general statistical principles from analyses actually documented for this study.

What does the endpoint count represent?

The primary outcome is the number of participants with HCV RNA “Not Detected” after 12 weeks. A count is an absolute number of participants meeting a criterion. To interpret it as a proportion, the count must be considered alongside the number of participants assessed under the endpoint definition. That denominator is not reported. It would be inappropriate to substitute the enrollment figure automatically, because the registry does not say that every enrolled participant had an evaluable result at the endpoint time.

In general, binary outcomes are often expressed as counts and proportions. A proportion can make the frequency easier to compare across groups, but it remains essential to know who was included and how missing assessments were treated. Those analysis details are not reported in the registry record. No primary outcome estimate is posted, so neither a study-specific proportion nor an uncertainty interval can be described.

What can a single-group study estimate?

A single-group study can describe outcomes observed among participants in that group. It cannot, by design, make a randomized comparison with a separate group. Randomization is generally used to help balance factors that could influence outcomes across treatment groups. With no control group, changes over time may reflect the intervention, the natural course of illness, other care, measurement variation, or other factors. The study design cannot separate these explanations through a between-group contrast.

Masking can reduce the opportunity for expectations to influence some aspects of care, assessment or reporting. The registry lists masking as none. The record does not report which outcome assessments, if any, involved subjective judgment, nor does it provide details that would support a more specific account of the consequences of that design feature.

What would uncertainty measures add?

In general, a confidence interval presents a range of values compatible with the observed data under a specified statistical model. It helps readers assess precision: an estimate alone does not show how uncertain it is. A p-value, in general, measures how compatible data are with a specified null hypothesis under the assumptions of a test; it is not a direct measure of clinical importance or the probability that a treatment works. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. No statistical test or model is documented.

For a count-based binary endpoint, the statistical method should be appropriate to the data structure and the question being asked. A one-group estimate and a two-group comparison answer different questions. Since no analysis is reported, the record does not identify which estimation procedure was used, how assumptions were checked, or whether any adjustment was applied. These details should not be inferred from the endpoint type alone.

How should planning illustrations be understood?

Sample-size illustrations based on an observed effect are planning exercises, not observed power. In general, such illustrations ask how many participants per arm might be needed under stated assumptions to detect an effect of a specified size. The stated assumptions for these illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Those assumptions describe the illustration, not a documented design plan for this single-group trial. The registry record does not report the sponsor’s sample-size justification.

Power is a design quantity based on assumptions about an effect, variability, sample size and analysis. It is not a measure of whether a completed study “had enough power” after seeing its result. In particular, a planning illustration cannot replace the missing primary outcome estimate, and it does not show that the trial reached a prespecified target. The record does not describe an intended power calculation or a planned randomized comparison.

For time-to-event outcomes, a common planning approach relates required information to event counts, while other outcome types may be expressed as participants per arm. The primary endpoint in this record is a participant count at a specified assessment time, not a reported time-to-event comparison. The registry does not report a time-to-event analysis for the primary outcome.

What analysis details remain unknown?

The record does not report an analysis population, missing-data approach, protocol deviations, covariate adjustments, interim analyses, or a statistical analysis plan. These omissions prevent readers from determining how the planned endpoint was translated into an analysis, whether assessments were available for all participants, or whether any alternative analyses were performed. The registry reports 3 outcome measures and 0 analyses. That identifies the amount of outcome-measure and analysis information posted in the record, but it does not establish what analyses may have been conducted outside the registry.

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("HCV Positive Group")
n      <- c(4)
events <- c(4)
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  HCV Positive Group  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and identifies sustained virologic response as the primary outcome. It reports 0 analyses. The outcome information summarized in the record does not establish results for the primary endpoint or the other outcome measures. A statistical analysis plan, including any prespecified hierarchy among outcomes, is not reported in the registry record.

In general, testing multiple outcomes can increase the chance of obtaining an apparently notable result by chance if each is treated as a separate confirmatory test. Methods such as a prespecified testing order or an adjustment to the testing threshold can address multiplicity, depending on the research question and plan. No multiplicity strategy is reported, so it cannot be said whether such a method was planned or applied. The missing analyses also mean there are no reported tests to interpret in light of multiplicity.

The registry does not report the number assessed for the primary endpoint or how missing HCV RNA results were handled. In general, missing outcome data can affect both the estimate and its uncertainty, especially if the reasons for missingness are related to participants’ health or outcome status. An analysis population, rules for excluding participants, and sensitivity analyses are not reported in the registry record. Enrollment of 9 does not establish that 9 participants contributed to the primary endpoint.

These gaps matter for interpretation, but they do not show that missing data or multiplicity necessarily changed a result. The registry record does not provide the information needed to assess those possibilities.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety summary lists the HCV Positive Group with 4 participants at risk for serious adverse events and 0 participants affected. It also lists 4 participants at risk for other adverse events and 1 affected. Deaths are listed as 0. These are the counts recorded in the registry summary; they are not a comparison between treatment groups, because the study has a single group.

In general, “at risk” identifies the denominator used for a safety category, while the affected count identifies participants recorded with an event in that category. The registry information does not describe the event definitions, observation periods, severity grading, relatedness assessments or whether participants could contribute to more than one category. The listed counts therefore should not be expanded into claims about event causes or overall safety.

No top serious adverse event terms are listed. The record does not report further detail that would explain the absence of terms, such as event narratives or attribution. These figures are a limited registry summary, not a full account of all possible adverse events during the study. The count of deaths is reported as 0, but the record does not provide additional context about follow-up or completeness of safety reporting.

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

The record specifies a study intended to examine sustained virologic response after a 12-week regimen of simeprevir, sofosbuvir and ribavirin in people with HCV genotype 1, cirrhosis and early clinical decompensation. It defines the primary endpoint using HCV RNA “Not Detected.” These details clarify the study question and the outcome criterion.

However, the registry record does not report the number of participants who met the primary endpoint, the number assessed, or an estimate of uncertainty. It therefore does not support a quantitative statement about the observed response in this study. It also does not report results for the stated aim of assessing hepatic improvement with HepQuant-SHUNT. No conclusion about observed hepatic change can be drawn from the posted information.

Even if endpoint results were available, the single-group, unmasked design would limit what could be inferred about the effect of the regimen relative to another treatment or no treatment. Without a concurrent control group, observed change cannot be separated from the natural course of illness, other influences or measurement variation through a randomized contrast. The study design is suitable for describing its group, but not for establishing a comparative treatment effect.

The terminated status does not reveal why the study stopped, and it should not be treated as evidence for or against the intervention. The record also does not report why analyses are absent or whether analyses were performed outside the registry. A careful interpretation distinguishes the documented design and endpoint definition from results and explanations that are not reported. The registry record supports the former; it does not provide the outcome evidence needed to characterize the primary result.

14. Why This Trial Matters Statistically

This study illustrates why a clearly stated endpoint and a reported endpoint result are both needed for statistical interpretation. The registry defines a concrete primary outcome: the number of participants with HCV RNA “Not Detected” after 12 weeks. Yet the outcome count and its assessment denominator are not reported. Knowing the endpoint definition clarifies what investigators intended to measure, but it does not tell readers what was observed.

The single-group design also highlights the difference between describing outcomes and estimating a comparative effect. A group’s outcome can be informative as a description, but a treatment contrast requires a comparator and a suitable design. The record identifies no randomized comparison, so the study cannot, on its own, distinguish treatment-associated outcomes from other changes over time.

The registry’s safety counts likewise require context. Counts and denominators are more interpretable than counts alone, but they remain a limited summary without event definitions, follow-up details and further clinical context. In general, careful statistical reading asks what was measured, in whom, over what period, and how missing observations and uncertainty were handled. Several of those details are not reported in the registry record.

Finally, the record’s status and its absence of posted analyses show why study conduct and study results should not be conflated. Termination does not identify the reason for stopping or determine the meaning of an unreported outcome. Statistical interpretation depends on the evidence actually reported, including the estimate and its precision, rather than on the stated aims alone.

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.

Several limitations specific to this record constrain interpretation. First, it describes a single-group study with no comparator and no masking. There is therefore no concurrent control against which to estimate a relative effect, and no basis for a randomized treatment contrast. Findings from a single group, if reported, would be descriptive rather than a controlled comparison.

Second, although enrollment is listed as 9, the registry does not report how many participants were assessed for the primary endpoint or included in an analysis. The primary outcome count is also absent. Without those details, neither the endpoint result nor its precision can be evaluated. The record does not report missing-data handling, an analysis population, or sensitivity analyses.

Third, the study is marked terminated, but the reason is not reported in the registry record. The record gives a primary completion date but does not establish whether the planned outcome collection was complete, why the study ended, or whether all intended analyses were conducted. The reported 0 analyses indicate that no analyses are posted in the summarized record; they do not establish what may have occurred outside it.

Fourth, the registry describes hepatic improvement as an aim involving HepQuant-SHUNT, but results and operational details for that measure are not reported. Details about treatment delivery, adherence, dose changes, eligibility criteria beyond those stated, and outcome assessment procedures are also not reported in the registry record. These omissions limit assessment of how closely the observed study conduct, if available, would correspond to the stated aims.

Finally, the safety information is a brief count summary without reported event terms or additional context. Taken together, the limitations are not evidence that the intervention had a particular effect; they indicate that the posted information is insufficient to assess the study’s clinical outcomes in depth.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Reversal of Hepatic Impairment in Patients With Hepatitis C Virus (HCV) and Early Decompensation of Cirrhosis — NCT02455167.
• Registry record last updated 2021-09-13; status last verified 2021-08.
• Results first posted 2021-09-13.
• 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

NCT02455167 is a phase 3, single-group study sponsored by the University of Colorado, Denver. It enrolled 9 and is listed as terminated. The recorded start is 2015-05, with primary completion on 2016-07-18. The population described is people with HCV genotype 1, cirrhosis and early clinical decompensation, with the official title specifying MELD 10 or less.

The intervention combines simeprevir, sofosbuvir and ribavirin for 12 weeks. The primary endpoint is the count of participants with HCV RNA “Not Detected” after 12 weeks. The registry lists 3 outcome measures and 0 analyses. It does not report the primary endpoint result, its denominator, or the reason for termination. Safety counts list 0 serious adverse events among 4 at risk, 1 other adverse event among 4 at risk, and 0 deaths.