An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients (NCT01467505), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12).

2. Clinical Question

The clinical question is about the observed response during a combination regimen in a post-transplant population, not about a randomized estimate of the regimen’s effect relative to another treatment. The immunosuppressant categories describe participants’ baseline regimens; they do not establish comparable groups. Their outcomes could reflect differences in participant characteristics or care as well as differences related to the study regimen.

The stated endpoint is a laboratory-defined measure at a specified follow-up time. It does not by itself answer questions about longer-term outcomes, all treatment-related harms, or how the regimen compares with alternatives. Those questions require results and study features that are not reported in the registry record.

3. Trial Design

The registry identifies this as a phase 2, open-label study with no masking, non-randomized allocation, and a single-group model. It lists an enrollment of 61 and a status of terminated. The study started in 2012-02, and primary completion is listed as 2014-04. The reason for termination is not reported in the registry record.

The study concerned participants with chronic genotype 1 HCV infection following liver transplantation. The regimen combined telaprevir, pegylated interferon alfa-2a, and ribavirin, alongside an immunosuppressant regimen. The brief summary describes a 48-week total treatment duration. The registry lists tacrolimus-based and cyclosporine-based immunosuppressant groups, but the arm descriptions are incomplete in the registry record, so additional regimen details cannot be established from it.

Open-label means masking was not used; participants and study personnel were not kept unaware of the assigned study treatment. In this study, the registry also says allocation was non-randomized. Thus, the listed immunosuppressant groups should not be read as randomized treatment arms or as like-for-like controls. Baseline immunosuppressant use may be associated with differences between participants, and the record does not describe an adjusted comparison addressing such differences.

The study’s status and its completion dates describe administrative and operational aspects, not the direction or quality of its results. Termination alone does not establish why the study stopped or whether the planned endpoint was assessed. The reason for termination, any protocol changes, and the extent to which the planned study was completed are not reported in the registry record.

The registry lists 13 outcome measures, including SVR12 as the primary outcome and additional virologic, pharmacokinetic, immunosuppressant, and rejection outcomes. It lists no analyses. A complete statistical analysis plan, including any prespecified comparisons or handling of incomplete observations, 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: Efficacy analyses were reported separately as per immunosuppressant regimen (reporting arms) and also separately as per prior response (in categories) (Treatment-Naive, Prior Relapser, Prior Null Responder, Prior Partial Responder, Uncategorized as well as for Total Participants), unless otherwise specified.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Set included all participants who received at least 1 dose of study drug. Here, n = participants evaluable for specified category for each arm, respectively.

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: Full analysis set included all participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12), measured over 12 weeks after last planned dose of study drug (up to Week 60).

The primary endpoint is the percentage of participants with a sustained viral response 12 weeks after the last planned dose of study drug, abbreviated SVR12. The registry defines response as an HCV RNA level below the assay’s lower limit of quantification at that follow-up. The stated assay was the Roche TaqMan HCV RNA assay, with a lower limit of quantification of 25 international units per milliliter. The timeframe is 12 weeks after the last planned dose, up to Week 60.

SVR12 is a binary outcome at the participant level: each evaluable participant is classified according to whether the specified laboratory threshold is met at the specified time. Reporting a percentage can make the frequency of this defined response easier to interpret than reporting laboratory values alone. It does not mean that every participant has the same underlying viral course, nor does it describe the timing of response or changes between visits.

Interpretation depends on who is included in the denominator and how missing or unevaluable measurements are handled. The registry says the Safety Set includes participants who received at least one dose and that the number evaluable for a category can vary by group. The detailed endpoint result, its denominator, and the handling of missing endpoint measurements are not reported in the registry record. Without those details, the endpoint definition can be described, but the observed response frequency cannot be evaluated.

SVR12 is not a complete summary of treatment experience. The registry separately lists outcomes such as SVR24, virologic failure, relapse, and rejection, but their results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General explanation: the main statistical challenge in a study like this is to describe the observed outcomes accurately while distinguishing description from causal comparison. The registry identifies a non-randomized, open-label, single-group design. It lists immunosuppressant-based groups, but those groups are not randomized comparators. Random allocation, when used, helps balance measured and unmeasured participant characteristics on average. Without it, group differences can reflect the participants who entered each group as well as any treatment-related differences.

What does the primary endpoint estimate?

SVR12 is a binary endpoint: participants either satisfy the laboratory definition at the specified follow-up or do not. A percentage summarizes the proportion meeting that definition among the participants included in the relevant denominator. The registry states that the Safety Set includes participants who received at least one dose and that the number evaluable for a category may differ by group. It does not report the SVR12 numerator, denominator, or percentage. Therefore, neither the observed proportion nor its uncertainty can be interpreted from the registry record.

For a binary outcome, a confidence interval is commonly used to express uncertainty around an estimated proportion or a contrast between proportions. General explanation: intervals are wider when information is less precise and narrower when information is more precise, subject to the analysis method and assumptions. An interval is not a guarantee that the true value lies within its limits. No SVR12 confidence interval or other uncertainty measure is reported in the registry record.

Why does the design matter for comparisons?

In a randomized comparison, assignment is determined by chance, supporting a causal interpretation when the trial is conducted and analyzed appropriately. Here, allocation is listed as non-randomized, and the study is classified as single-group. The tacrolimus and cyclosporine descriptions identify baseline immunosuppressant regimens, not randomly assigned study treatments. Any comparison between those categories would be vulnerable to confounding: characteristics associated with the choice or use of an immunosuppressant could also be associated with outcomes.

Open-label status means that masking was absent. General explanation: awareness of treatment can influence co-interventions, reporting of subjective outcomes, and decisions about continued treatment or assessments. Laboratory-defined endpoints may be less subjective than symptom reports, but open-label conduct does not remove every potential source of bias. The registry does not report whether endpoint assessment or laboratory procedures were masked.

How should safety counts be read?

The serious adverse event summary gives participants at risk and participants affected for each listed group. It reports 11 affected among 51 at risk for the tacrolimus group and 3 affected among 10 at risk for the cyclosporine group. These are descriptive group summaries. They do not account for differences in exposure time, participant characteristics, or other possible causes of events, and they do not establish a comparative treatment effect. The record does not report deaths for these groups. A missing death count should not be interpreted as evidence that no deaths occurred.

General explanation: adverse event summaries may count participants with at least one event, events themselves, or events within particular categories. These are not interchangeable quantities. A participant may experience more than one event, so participant counts should not be treated as event totals. The record’s serious-event fields describe participants affected and at risk; it also lists selected serious-event terms with percentages. The record does not specify in that term list how events were distributed between groups.

What can the analysis record establish?

The registry lists 13 outcome measures and no analyses. That does not supply a statistical analysis plan. The plan for covariate adjustment, the analysis method for the primary endpoint, any interim analyses, and any sample-size justification are not reported in the registry record. It is therefore not possible to determine whether analyses were prespecified, how they were conducted, or whether they addressed the non-randomized group structure.

General explanation: analysis populations should be defined before results are interpreted. A safety population based on receiving study drug can be suitable for describing treatment-emergent events, while an efficacy analysis may use a different population or endpoint-specific evaluability rules. Different denominators can change a reported percentage. Because the registry notes that evaluable numbers may vary by category, each outcome needs its own population and denominator to be interpreted correctly.

Missing outcome data can affect a binary response estimate, especially if missingness is related to response or to reasons for discontinuation. General explanation: complete-case summaries describe participants with observed measurements, while imputation or other approaches make additional assumptions about unobserved outcomes. The registry record does not report how missing SVR12 measurements, early discontinuations, or unevaluable assessments were handled.

Multiplicity concerns arise when a study examines multiple outcomes or comparisons. General explanation: testing many hypotheses can increase the chance of at least one false-positive result if no adjustment or hierarchy is used. The registry lists a primary outcome and secondary outcomes, but a multiplicity strategy and the order of hypothesis testing are not reported. Since results and analyses are not listed, there is no basis to judge whether multiplicity adjustments were made.

Sample-size planning is distinct from observed results. A planning illustration based on an observed effect is not the trial’s original design justification and is not observed power. The registry does not report the study’s original sample-size assumptions or justification. Such illustrations should be understood only as hypothetical planning scenarios, not as evidence that the study had a particular probability of detecting an effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists SVR12 as the primary outcome and lists secondary outcomes that include SVR24, rapid and extended rapid viral response, on-treatment virologic failure, relapse, pharmacokinetics, immunosuppressant dose titration, and biopsy-confirmed and treated rejection. The record lists 13 outcome measures overall. The results for these outcomes are not reported in the registry record.

Having a designated primary outcome helps identify the main clinical question, but it does not by itself explain how multiple outcomes or comparisons were handled statistically. A plan for controlling the chance of false-positive findings across outcomes, or a hierarchy for interpreting secondary results, is not reported in the registry record. No analyses are listed, so the record does not support a review of any multiplicity adjustment.

The primary outcome population is described as the Safety Set, including participants who received at least one dose. The record also says that the number evaluable for a specified category can vary by group. It does not report the endpoint-specific denominators or the number of missing SVR12 measurements. The approach to missing values, discontinuations, or participants without an assessment at the required follow-up is not reported in the registry record.

These omissions matter because a percentage depends on which participants contribute to its denominator, and conclusions can depend on how missing outcomes are treated. General explanation: if outcome availability is related to prognosis or treatment experience, restricting analysis to participants with observed measurements can produce a biased estimate. Different missing-data methods also rely on different assumptions. Without the analysis population details and missing-data rules, the primary endpoint cannot be fully assessed.

The record does not report interim analyses, the statistical analysis plan, or the original sample-size justification. These should not be inferred from the enrollment figure or from any planning illustration.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: herpes zoster (10.0%), pneumonia (10.0%), coronary artery disease (10.0%), pleural effusion (10.0%), nausea (7.8%).

The registry reports serious adverse event counts for the listed immunosuppressant groups. In the tacrolimus group, 11 participants were affected among 51 at risk; in the cyclosporine group, 3 were affected among 10 at risk. These figures describe participants with serious adverse events in the registry’s group summaries. They are not event totals and do not establish that the groups had comparable follow-up or participant characteristics.

The record also lists Herpes zoster, Pneumonia, Coronary artery disease, and Pleural effusion at 10.0%, and Nausea and Vomiting at 7.8%, among its top serious terms. The record does not state in this list how those terms were distributed by immunosuppressant group. The percentages should therefore be read as reported term summaries, not as a group-specific comparison.

For other adverse events, the record reports 51 affected among 51 at risk in the tacrolimus group and 10 among 10 at risk in the cyclosporine group. A participant may experience multiple events, so affected-participant counts do not convey the number of events or their severity distribution. The death fields are not populated; deaths are not reported in the registry record. That is not equivalent to a reported finding of no deaths.

Because the study was non-randomized and open-label, these safety summaries are descriptive. They cannot establish that a treatment caused or prevented an event, or support a direct safety ranking of the groups.

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

The registry record establishes that a phase 2, open-label, non-randomized study was conducted to assess telaprevir with pegylated interferon alfa-2a and ribavirin for chronic genotype 1 HCV infection following liver transplantation. It identifies SVR12 as the primary endpoint and provides its laboratory definition and follow-up time. It also provides selected serious adverse event counts.

The record does not report the SVR12 result. It therefore does not show what percentage met the primary endpoint, how precise that estimate was, or whether outcomes differed between the listed immunosuppressant groups. It also does not report the results for the listed secondary outcomes. The missing result should not be interpreted as a finding of no response or as proof that the regimen did not have an effect.

The design does not provide a randomized control comparison. The tacrolimus-based and cyclosporine-based groups are not like-for-like controls by virtue of being listed separately; assignment was non-randomized and the model is classified as single-group. Even if group-specific outcomes were available, differences would need cautious interpretation because they could reflect baseline differences or other factors.

The safety counts describe participants recorded with serious adverse events, but do not establish cause. The record does not report deaths in those group summaries, and a missing field cannot establish that no deaths occurred. The listed serious-event terms likewise do not provide enough information for a group comparison.

General explanation: statistical evidence is strongest when the endpoint, population, analysis method, and uncertainty are all clear and when the design supports the intended comparison. Here, the endpoint definition and some design details are available, but the primary result, uncertainty, analysis details, and reason for termination are not reported in the registry record. The defensible interpretation is therefore limited to describing the study and the posted safety counts, not drawing conclusions about efficacy or comparative safety.

13. Why This Trial Matters Statistically

This study raises statistical issues that are especially important in clinical research involving transplantation. The primary outcome is a laboratory-defined response after treatment, while the participants were also receiving immunosuppressant regimens. That setting makes it important to distinguish the treatment question from differences associated with baseline clinical management. The registry lists tacrolimus-based and cyclosporine-based groups, but non-randomized allocation does not make them exchangeable comparison groups.

The record also illustrates why a clear endpoint definition is necessary but not sufficient. It specifies the timing of SVR12 and the assay threshold, so the target outcome is understandable. Yet the result, denominator, uncertainty, and missing-data approach are not reported. Without these elements, readers cannot judge the response frequency or its precision.

Safety interpretation requires similar care. The registry gives serious-event participant counts and at-risk counts, but those descriptive summaries do not control for differences between groups or exposure. The serious-event term list adds clinical detail, but does not support a group-specific contrast. Counts and percentages are informative only when their population and meaning are clear.

The terminated status makes transparent reporting particularly relevant, but it does not explain why the study stopped or what analyses were completed. The reason for termination and the primary endpoint result are not reported in the registry record. A status label cannot substitute for outcome reporting.

More broadly, the record shows how design, endpoint definition, analysis population, missingness, and multiplicity all shape interpretation. A complete account would need to connect those elements to the observed results. In their absence, statistical restraint is essential: the study’s purpose and some safety information can be described, but the efficacy question remains unanswered by the posted registry results.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is that the registry record does not report the primary SVR12 result or results for the listed secondary outcomes. It also provides no primary endpoint estimate, confidence interval, or p-value. The study’s efficacy findings therefore cannot be assessed from the record.

The study was open-label, non-randomized, and classified as single-group. Its tacrolimus-based and cyclosporine-based groups should not be treated as randomized controls. The record does not describe an adjusted comparison, and it does not report enough information to assess whether group differences in participant characteristics were addressed.

The record describes the Safety Set and notes that the number evaluable can vary by outcome category, but does not give the SVR12 denominator or explain missing-data handling. It also does not report the statistical analysis plan, multiplicity approach, interim analyses, or original sample-size justification. These omissions limit assessment of how the endpoint was analyzed and how secondary outcomes should be interpreted.

The arm descriptions are incomplete, and the reason for termination is not reported in the registry record. The safety summary does not report deaths in its group fields; this does not establish that no deaths occurred. Serious adverse event terms are listed with percentages but are not attributed to a particular group in that list. Safety findings should consequently remain descriptive and should not be read as causal or comparative conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients — NCT01467505.
• Registry record last updated 2015-06-18; status last verified 2015-06.
• Results first posted 2015-06-18.
• 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.

18. Record Summary

The registry record describes a phase 2, open-label study of telaprevir, pegylated interferon alfa-2a, and ribavirin in participants with chronic genotype 1 HCV infection following liver transplantation. It is classified as non-randomized and single-group, with tacrolimus-based and cyclosporine-based immunosuppressant groups listed. Enrollment is 61, and the status is terminated.

The primary outcome is SVR12, defined using HCV RNA below the assay’s lower limit of quantification 12 weeks after the last planned dose. The primary result and the results of the listed secondary outcomes are not reported in the registry record. Some serious adverse event counts are reported by group, but they do not establish comparative or causal safety findings.

Important details—including the reason for termination, endpoint-specific denominators, missing-data methods, and the statistical analysis plan—are not reported in the registry record. Interpretation is therefore limited to the study design, endpoint definition, and descriptive safety information.