Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation (NCT01687257), a randomized phase 2 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12).

2. Clinical Question

The central randomized contrast is between participants assigned to SOF+RBV and participants assigned to observation. In the treatment group, the endpoint was assessed 12 weeks after stopping study treatment. For the observation group, the registry used a distinct definition: HCV RNA below the lower limit of quantitation for 12 consecutive weeks at any time during the observational period. That difference in timing and exposure context matters when interpreting the comparison.

The study also followed the observation group after it began SOF+RBV. Its results after treatment describe another treatment experience, but do not retain the initial randomized untreated comparison. The clinical question is therefore broader than a single parallel comparison, while the primary randomized evidence concerns treatment versus observation during the initial study period.

3. Trial Design

This was a phase 2, multicenter, open-label, randomized, parallel study with no masking. The registry records enrollment of 50 participants. The study was sponsored by Gilead Sciences, began in 2012-07, had primary completion in 2015-01, and is marked completed.

Participants were assigned in a 1:1 plan to one of two sequences. Group 1 received SOF+RBV for 48 weeks. Group 2 entered a 24-week observation period and then received SOF+RBV for 48 additional weeks. The posted primary endpoint includes the randomized treatment group and the observation period in Group 2. Separately, the results include Group 2 after it began treatment.

The registry describes an open-label study, so masking was not used. The parallel structure refers to the initially assigned study paths; it does not mean that Group 2 remained untreated throughout the period covered by all posted outcomes. Once that group started SOF+RBV, its results describe treatment after observation rather than a concurrent untreated comparison.

Enrollment was 25 in each initially randomized group for the primary endpoint. The posted result for Group 2 after treatment includes 21 participants. The registry record does not explain the difference in the number contributing to that result, and it does not report details about participant flow or missing outcome data. It also does not report the protocol’s sample-size justification, or a complete statistical analysis plan. Those details should not be inferred from the randomized allocation or enrollment figure.

The study listed secondary outcomes for later sustained virologic response, on-treatment virologic failure, viral relapse, hepatic venous pressure gradient, Child-Pugh-Turcotte score and Model for End Stage Liver Disease score. The posted registry results include numeric summaries for some, but not all, of these listed 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.

Before assignment: 63 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who were randomized to the 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.

Population: Participants who were randomized and received at least 1 dose of study drug

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12), measured over Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation).

The primary endpoint is the percentage of participants with sustained virologic response 12 weeks after discontinuing therapy, called SVR12. It is based on HCV RNA: for the treatment group, response required HCV RNA below the lower limit of quantitation, defined as 25 IU/mL, at 12 weeks after stopping study treatment. For the observation group, the registry instead defined response during observation as HCV RNA below that limit for 12 consecutive weeks at any time during the observational period.

SVR is used in HCV studies as a virologic outcome: it records whether the virus is below the specified measurement threshold at a defined follow-up time. It is not a direct measure of liver function, portal pressure, symptoms or every aspect of health. The other listed outcomes address some of those distinct questions, including liver pressure and liver-disease scores.

The timing and definitions are important. The treatment group’s result refers to assessment after a 48-week treatment course, while the comparison group’s primary result refers to an untreated observation period. Consequently, the primary percentage contrast should be read as a comparison of the registry-defined endpoint in those different study contexts, not as a comparison at the same point after identical treatment exposure. The registry record does not report a separate standardized endpoint definition that would make those contexts equivalent.

7. Results Posted in the Registry

• SOF+RBV (Group 1): 72.0% (18/25) versus 0.0% (0/25) on control; risk difference 72.0 percentage points (95% CI 54.4 to 89.6); unadjusted two-proportion z-test p = <0.001.
• SOF+RBV (Group 2): 71.4% (15/21) versus 0.0% (0/25) on control; risk difference 71.4 percentage points (95% CI 52.1 to 90.8); unadjusted two-proportion z-test p = <0.001.

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.

Percentage of Participants Experiencing On-Treatment Virologic Failure

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • SOF+RBV (Group 2): 0.0% (0/21) versus 8.0% (2/25) on control; risk difference -8.0 percentage points (95% CI -18.6 to 2.6); unadjusted two-proportion z-test p = 0.185.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SOF+RBV (Group 2) and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants Experiencing Viral Relapse

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • SOF+RBV (Group 2): 23.8% (5/21) versus 17.4% (4/23) on control; risk difference 6.4 percentage points (95% CI -17.5 to 30.3), risk ratio 1.37 (0.42–4.43); unadjusted two-proportion z-test p = 0.598.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SOF+RBV (Group 2) and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at End of Treatment

• 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:
  • SOF+RBV (Group 1): mean -1.60 versus 0.50 on control; difference -2.10 (95% CI -4.55 to 0.35), standardized effect d = -0.55; z-test p = 0.093.
  • SOF+RBV (Group 2): mean -0.40 versus 0.50 on control; difference -0.90 (95% CI -2.54 to 0.74), standardized effect d = -0.35; z-test p = 0.284.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SOF+RBV (Group 1) 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 SOF+RBV (Group 2) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the study beyond the primary SVR12 measure. They cover later sustained virologic response, on-treatment virologic failure, viral relapse, hepatic venous pressure gradient and liver-disease scores. These outcomes address different features of viral response and liver status, so they should not be treated as interchangeable confirmations of the primary endpoint.

The posted secondary results include numeric summaries for on-treatment virologic failure, viral relapse and change in hepatic venous pressure gradient. Their comparisons do not establish a uniform pattern across all dimensions: they describe separate outcomes with distinct denominators and timeframes. The registry also lists SVR at other post-treatment times and changes in Child-Pugh-Turcotte and Model for End Stage Liver Disease scores, but numeric results for those listed outcomes are not reported in the registry record.

Secondary outcomes can help describe whether the primary response finding is accompanied by changes in other measured outcomes, but they do not independently validate the primary contrast. In this record, no formal analysis is listed for the secondary outcomes, and the comparisons are unadjusted recalculations. Their interpretation is therefore more exploratory than a result from a prespecified, multiplicity-controlled confirmatory analysis.

When many endpoints are examined, chance alone can produce apparently notable findings among some comparisons. In general, multiplicity procedures or a prespecified testing hierarchy can help control the interpretation of repeated testing. Neither is reported in the registry record. The secondary estimates remain useful descriptions of the posted data, but they carry less inferential weight than a single primary outcome specified in advance. The registry record does not report whether all listed secondary outcomes were analyzed under a common plan or how any missing measurements were treated.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With SVR at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48)
• Percentage of Participants Experiencing On-Treatment Virologic Failure
• Percentage of Participants Experiencing Viral Relapse
• Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at End of Treatment
• Change From Baseline in Child-Pugh-Turcotte (CPT) Score
• Change From Baseline in Model for End Stage Liver Disease (MELD) Scores

9. Statistical Interpretation

10. Statistical Methods Explained

The posted results use percentages for the binary primary outcome: each participant either met the registry’s SVR definition or did not. The primary endpoint is reported as 72.0% for SOF+RBV (Group 1), 0.0% for the Group 2 observation period, and 71.4% for SOF+RBV (Group 2). The corresponding participant counts are 18 of 25, 0 of 25, and 15 of 21. Counts are useful alongside percentages because they show the amount of participant information behind each proportion.

What does a risk difference mean?

For a binary outcome, a risk difference subtracts one group’s event proportion from the other group’s event proportion. Here, the comparison is expressed as the treatment-group proportion minus the corresponding observation-period proportion. A positive value indicates a higher observed response proportion in the treatment group under the stated coding. The primary recalculated risk difference is 0.72; the comparison for Group 2 after treatment is 0.714. These are absolute contrasts in proportions, not relative changes.

In general, absolute contrasts are often easier to interpret alongside the original group percentages than relative measures, because they describe the difference on the outcome’s own proportion scale. They still depend on which groups, participants, and endpoint timing are being compared. In this study, the Group 2 observation interval and its later treatment interval are distinct contexts, so the same arithmetic contrast should not be mistaken for the same design contrast.

How should the p-values be read?

The reported comparison p-values are unadjusted recalculations from the posted group summaries. In general, a p-value measures how compatible the observed data are with a specified null model, conditional on the model and calculation used. It is not the probability that a treatment is effective, nor does it measure the size or clinical importance of an effect. The primary comparison has p < 0.001. The registry record does not report a formal sponsor analysis or specify the test used for these comparisons, so the p-values should not be attributed to an unreported analysis plan.

The registry record lists no reported analyses. The comparisons should consequently be distinguished from formal inferential results that might account for covariates, repeated measurements, stratification or other design features. No such adjustment is reported. The study’s phase, allocation and masking are recorded, but those design fields do not identify the exact statistical test or model.

What is a confidence interval?

In general, a confidence interval gives a range of values compatible with the observed data under a stated statistical procedure. It expresses uncertainty in the estimated contrast, rather than a range containing a guaranteed share of individual participant outcomes. The primary recalculated interval for the risk difference extends from 0.544 to 0.896. It is above zero, consistent with the small unadjusted p-value for this comparison. The interval does not account for unreported sources of uncertainty, such as missing-data handling or departures from the calculation’s assumptions.

All comparisons should be read in light of the endpoint definition. The treatment-group endpoint was assessed after therapy ended. The observation-group endpoint required a qualifying period of low HCV RNA during observation. Even where proportions are compared on the same binary scale, different timing and exposure can influence what the contrast means.

How do the planning illustrations differ from observed results?

The registry includes planning illustrations for selected secondary comparisons. These are not observed power and are not the trial’s own sample-size justification. They use the observed effect as a starting point, consider the stated fractions of that effect, and assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The figures are illustrative participant requirements per arm for the specified power targets, not a prediction that a future study will achieve those effects or power.

In general, planning from an observed effect can be unstable, particularly when the initial study is small: the observed estimate may not represent the effect a later study will see. A planning calculation is therefore best treated as a scenario, not as confirmation of the initial result. The registry record does not report the assumptions or justification used to design the original trial.

Finally, secondary outcomes raise issues beyond the calculations for any single endpoint. Multiple outcomes and comparisons increase the chance that some unadjusted results will appear notable by chance. The record does not report a multiplicity adjustment or a hierarchy of confirmatory secondary hypotheses. Those limitations affect the weight of secondary comparisons, even when their estimates are informative descriptively.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.72, with a 95% confidence interval from 0.544 to 0.896. That interval is entirely above zero and indicates that, under the unadjusted comparison calculation, the data are compatible with a positive difference across the range stated. It is not a guarantee that the true difference lies within those limits, and it does not capture every uncertainty relevant to applying the result beyond this study.

The interval’s width reflects uncertainty in estimating the contrast from the available participant counts. The primary groups each include 25 participants, and the outcome counts are 18 and 0. With limited group sizes, observed proportions can be sensitive to the outcomes of a small number of participants. A confidence interval gives more information about that sampling uncertainty than a point estimate alone.

The interval does not resolve whether different endpoint timing or treatment exposure affects interpretation. Nor does it address unreported missing-data procedures, the representativeness of participants, or outcomes not measured by SVR12. Statistical precision within the stated calculation is distinct from generalizability and from clinical importance.

The result for Group 2 after treatment has a recalculated risk difference of 0.714 and a 95% confidence interval from 0.521 to 0.907. It too is above zero under the stated comparison, but it describes a later treatment period with 21 participants, not the same concurrent randomized comparison as the primary contrast. The registry record does not report formal analysis methods that would support a more elaborate precision interpretation.

In general, confidence intervals are most useful when considered together with the endpoint definition, design and data completeness. A narrow or non-zero interval cannot correct for an analysis population that is unclear, unreported missing-data handling, or systematic differences in measurement. Here, the interval quantifies uncertainty in the recalculated contrast, not uncertainty about every aspect of the study.

12. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists several secondary outcomes, but it does not report a multiplicity strategy, a confirmatory testing hierarchy, or a comprehensive statistical analysis plan. When several outcomes are examined, unadjusted p-values do not account for the increased opportunity to see apparently unusual results by chance. The secondary comparisons should therefore be treated as descriptive or exploratory rather than as a set of independent confirmatory findings.

The record reports no formal analyses. The posted comparisons are unadjusted recalculations from group summaries; no adjustment for baseline characteristics, stratification factors or other covariates is reported. The registry record also does not state whether interim analyses were planned or performed. These details are not inferable from the reported p-values or confidence intervals.

The primary endpoint population is described as participants randomized to the study, and the initial groups each have 25 participants in the posted primary result. However, the registry does not describe an intention-to-treat rule in detail, specify a per-protocol population, or explain how participants with unavailable outcome measurements were handled. The Group 2 treatment result includes 21 participants; why that denominator differs from its initial randomized group is not reported in the registry record.

Missing-data choices can affect binary outcome percentages. In general, excluding participants without an observed endpoint, counting them as nonresponders, or using another method can lead to different estimates. No such approach is reported, and no sensitivity analysis addressing missing outcomes is listed. The observed denominators should therefore be read as posted, without assuming how they relate to every randomized participant.

The record does not report a sample-size justification for the original trial. Planning illustrations based on observed effects are separate from that missing design rationale and should not be interpreted as observed power. Taken together, these reporting gaps limit assessment of whether the analyses followed a prespecified plan and how robust the results are to analytic choices.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ascites (4.8%), gastrointestinal haemorrhage (4.8%), oesophageal varices haemorrhage (4.8%), pyrexia (4.8%), cholecystitis (4.8%).

The registry reports serious adverse events for 4 of 25 participants in SOF+RBV Group 1, 3 of 25 participants during the Group 2 observation period, and 6 of 21 participants during Group 2 SOF+RBV treatment. These are counts of participants reported as affected in the listed periods; they are not a comparison adjusted for duration or other participant differences.

The serious-event terms listed include ascites, gastrointestinal haemorrhage, oesophageal varices haemorrhage, pyrexia, cholecystitis and hepatic failure, each reported at 4.8%. The record does not provide enough detail in these summaries to establish the timing, severity beyond the serious classification, relationship to study treatment, or whether participants experienced more than one listed event. Death counts are not reported in the registry record.

In general, safety counts in a small study are descriptive. Differences across groups do not by themselves show that treatment caused or prevented an event, particularly when the groups represent different periods and exposure. These figures should be read as the registry’s reported safety information, not as a standalone comparative safety analysis.

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

The primary result describes a higher observed SVR12 proportion in the randomized SOF+RBV group than in the randomized observation group during the primary comparison. The recalculated risk difference and its confidence interval indicate a clear unadjusted contrast in those posted data. The later SOF+RBV result in Group 2 provides a separate description after that group began treatment.

These results do not, on their own, establish how the regimen would perform in every person with chronic HCV, cirrhosis and portal hypertension. The trial enrolled 50 participants, and the primary endpoint population is limited to the randomized study participants. The record does not report subgroup results for compensated versus decompensated disease, so the overall percentages cannot establish whether the result differs by disease status.

SVR12 measures HCV RNA relative to a defined assay threshold at a specified time. It is not a complete measure of liver status or safety, and it does not substitute for the separately listed measures of portal pressure and liver-disease scores. Numeric results for some listed outcomes are not reported in the registry record. The primary percentages therefore answer a narrower virologic question than the full range of clinical questions raised by the study population.

The trial was open-label and the primary endpoint definitions differ in timing and context between treatment and observation. Those features do not erase the recorded randomized comparison, but they are important to its interpretation. Missing-data handling, detailed analysis populations and formal analysis methods are not reported in the registry record. The recalculated inferential statistics should not be presented as a substitute for an unreported sponsor analysis.

In general, a statistically distinct result is not synonymous with clinical importance, nor does it guarantee a particular outcome for an individual. The registry results support description of the trial’s measured outcomes; they do not provide medical advice or establish effects beyond the study’s participants, endpoint definitions and follow-up.

15. Why This Trial Matters Statistically

This trial is statistically instructive because its randomized structure contains both an active-treatment period and an initial untreated observation period, followed by treatment for the observation group. That creates distinct comparisons: the randomized treatment-versus-observation contrast and the later treatment experience in Group 2. Keeping those comparisons separate prevents a post-observation result from being mistaken for a concurrent randomized control contrast.

The primary outcome is binary and is reported with both percentages and participant counts. The risk difference gives an absolute comparison, while its confidence interval makes the sampling uncertainty visible. The observed contrast is large on the scale of the reported proportions, but the trial remains small, and the interval and denominators matter when judging precision.

The study also illustrates why endpoint definitions and timing deserve attention. The treatment group’s SVR12 assessment follows treatment discontinuation, whereas the observation group’s response is defined during an untreated period. Even when both are summarized as percentages, their different contexts should be part of the statistical interpretation.

Finally, the record demonstrates the distinction between posted results and a full analysis report. No formal analyses, multiplicity strategy, detailed missing-data procedure or original sample-size justification is reported. Secondary estimates and planning illustrations can still be useful, but their inferential role should not be overstated. These design and reporting features are relevant when evaluating how much weight to place on a point estimate, p-value or planning scenario.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several limitations are specific to the information recorded for this study. The primary comparison places a 48-week treatment course against an initial 24-week observation period, and the endpoint timing and definition differ between those settings. The Group 2 treatment result occurs after observation and is not a concurrent randomized untreated comparison.

The study enrolled 50 participants, with 25 in each initial group. The Group 2 treatment result includes 21 participants, but the registry record does not explain this denominator. It does not report participant flow, reasons for missing outcomes, or how missing data were handled. The primary population is described as randomized participants, but detailed analysis-population rules are not reported.

The registry does not provide subgroup results by compensated or decompensated status, despite including participants with or without liver decompensation. Numeric findings for some listed secondary outcomes are also not reported in the registry record. This limits the extent to which the posted results address the full set of questions suggested by the study population and outcome list.

Formal statistical methods, multiplicity handling, interim analysis details and the original sample-size justification are not reported. The posted unadjusted recalculations do not replace those missing details. The open-label design and the small numbers also mean that estimates should be interpreted with attention to potential measurement and sampling uncertainty. These limitations describe the boundaries of the registry record; they do not establish that an unreported procedure was or was not undertaken.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation — NCT01687257.
• Registry record last updated 2016-09-16; status last verified 2016-08.
• Results first posted 2016-02-24.
• 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.

20. Record Summary

NCT01687257 is a completed phase 2, multicenter, open-label, randomized parallel study sponsored by Gilead Sciences. It enrolled 50 adults with chronic HCV, cirrhosis and portal hypertension, with or without liver decompensation. Group 1 received SOF+RBV for 48 weeks; Group 2 had 24 weeks of observation followed by 48 weeks of SOF+RBV.

The primary endpoint was SVR12, defined using HCV RNA below the lower limit of quantitation. The registry reports 72.0% for Group 1 and 0.0% during Group 2 observation; the later Group 2 treatment result is 71.4%. Secondary outcomes include virologic and liver-status measures, with numeric results posted for some outcomes. Formal analyses and details of missing-data handling are not reported in the registry record.