Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant (NCT02945150), a na phase 4 study. The primary outcome is Number of Participants With Undetectable HCV RNA at SVR12.

2. Clinical Question

The study’s stated purpose was proof of concept for accepting HCV-positive kidneys for HCV-negative recipients while using preemptive treatment to prevent HCV transmission after transplantation. The intervention was initiated in relation to the transplant rather than described as treatment begun after a documented period of infection. That timing is central to the question: the endpoint concerns whether viral RNA was undetectable at a specified follow-up point after treatment.

The registry record does not report the observed number of participants with undetectable HCV RNA at SVR12. It also does not report a treatment-effect estimate or a comparison with recipients managed without the study intervention. The clinical question can therefore be described from the registered objective and endpoint, but the posted record does not give the primary outcome needed to assess the observed virologic result.

3. Trial Design

This was a Phase 4, open-label, single-group study described as a single-center proof-of-concept investigation. The registry lists enrollment of 8 and status as completed. The start date is 2017-02-01, and the primary completion date is 2019-08-20. Massachusetts General Hospital is listed as the sponsor.

All participants were in the elbasvir/grazoprevir treatment group for recipients of HCV-positive kidney transplants. The intervention was the fixed-dose combination of elbasvir 50mg and grazoprevir 100mg. The arm description states that the first dose was given on-call to the operating room and treatment continued daily for 12 weeks. The primary endpoint description, however, refers to treatment lasting 12–16 weeks. The registry record does not explain this difference, so the treatment duration should not be treated as fully consistent across the record.

Allocation is listed as NA, and masking is listed as none. There is no randomized allocation or masking scheme described. Because there is a single treatment group, the study can describe outcomes observed among enrolled recipients, but cannot by itself separate the intervention’s effects from other factors that might influence outcomes after transplantation. No like-for-like control group is reported.

The listed primary endpoint is the number of participants with undetectable HCV RNA at SVR12, with a timeframe of 12 weeks post-treatment and 24 weeks post-transplant. A secondary outcome tracks undetectable serum HCV RNA at several stated study days, from Study Day 7 through Study Day 365. The registry record identifies these outcome measures but does not report their observed results or the details of how participants were analyzed.

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: 33 patients signed consent for the study. Of those, 23 patients were deemed "ready" for transplant and were put on the waitlist for a HCV kidney (10 patients did not meet the "readiness" criteria for kidney transplantation). Of those, 8 patients were transplanted with an HCV+ kidney.

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 Number of Participants With Undetectable HCV RNA at SVR12, measured over 12 weeks post-treatment (24 weeks post-transplant).

The primary endpoint is the number of participants with undetectable HCV RNA at SVR12. The registry defines sustained virologic response at 12 weeks post-treatment as a negative HCV viral load. The stated timeframe is 12 weeks post-treatment, or 24 weeks post-transplant. This endpoint focuses on a laboratory measure of viral RNA at a specified follow-up point rather than on symptoms or a broader clinical outcome.

As a general statistical concept, a binary endpoint classifies each participant according to whether the defined condition is present or absent at the assessment point. Reporting the count of participants meeting the endpoint describes how often the recorded outcome occurred in the studied group. It does not, on its own, establish what would have happened to comparable participants under another treatment strategy. In a single-group study, that distinction matters because there is no concurrent control group to provide a direct contrast.

The registry record’s primary endpoint description refers to 12–16 weeks of elbasvir/grazoprevir treatment, while the arm description says daily treatment continued for 12 weeks. The registry does not clarify the difference. Most importantly, it does not report the observed primary endpoint count. The endpoint is specified, but its result and the precision of any estimated response proportion are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The information recorded describes a single-group study with a binary primary outcome. The outcome is whether a participant had undetectable HCV RNA at SVR12. For a binary endpoint, the basic descriptive result is the number of participants meeting the definition, considered in relation to the participants assessed. That description is meaningful only when the result and the relevant analysis population are reported. The registry record names the endpoint but does not report its observed count or the number assessed for it.

What can a single-group design estimate?

In general, a single-group study can estimate the frequency of an outcome among the participants who received the intervention and were assessed. It does not directly estimate a difference between intervention and control groups because no control group is included. A before-and-after or external comparison would require additional information and assumptions; neither is described in this record. The study’s open-label status also means that masking is not part of the listed design. The record does not explain whether outcome assessment involved any separate safeguards against assessment bias.

The single-group structure is not necessarily a defect for a proof-of-concept objective. It does, however, limit the kinds of statistical conclusions that can be drawn. An observed event count can describe the enrolled group, but cannot establish the counterfactual outcome that would have occurred under a different strategy. Interpretation should distinguish a descriptive response frequency from a comparative treatment effect.

Why does precision matter?

As a general statistical concept, a point estimate is the value calculated from the observed sample, while a confidence interval conveys uncertainty around that estimate under a statistical model. The interval’s width depends in part on the amount of information in the data and on the outcome frequency. With a limited enrollment, estimates may be uncertain even when the observed count is clearly stated. The registry record does not provide a point estimate or confidence interval for the primary endpoint, so neither the magnitude nor precision of that result can be assessed.

For a binary outcome, uncertainty is often expressed for a proportion or for a contrast between proportions. A contrast would require data for a comparator group, which this trial does not have. A proportion would require the observed endpoint count and an analysis denominator; these are not reported for the primary endpoint. No new estimate can be recovered from the endpoint title or the enrollment entry alone.

What do the planning assumptions mean?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the study was designed with those assumptions or that a particular sample size was justified by them. The registry record does not report the trial’s own sample-size justification.

A planning sample size is a prospective illustration of how much information a hypothetical future study might need under chosen assumptions. It is not an outcome of the present trial and must not be interpreted as observed power. The described planning approach assumes two arms, whereas this trial is recorded as single-group with allocation listed as NA. Its planning assumptions therefore do not create a comparator in the trial or convert its results into a randomized comparison. The record does not report numerical planning estimates or the observed effect on which they would depend.

In general, a significance level sets a decision threshold for a specified statistical test; it does not measure the probability that a treatment works. A two-sided test considers departures in either direction. The normal approximation is a mathematical method used in some sample-size calculations. Its suitability depends on the quantities and design being modeled, but those numerical details are not reported. No inferential test for the primary outcome is reported in the registry record.

How should repeated outcome assessments be understood?

The secondary outcome lists serum HCV RNA assessments at Study Day 7, 14, 28, 56, 84, 112, 168, 252, and 365. As a general matter, repeated measurements can describe how an outcome changes over time, but the method depends on the data structure and analysis objective. The registry record does not provide the results at these visits, the number of participants assessed at each visit, or an analysis approach for repeated measurements. Therefore, no pattern over time can be inferred from the list of assessment points alone.

The record lists 2 outcome measures and 0 analyses. The absence of analyses in the registry record means that adjusted estimates, test statistics, and model-based results are not available there. It would be inappropriate to substitute an unadjusted calculation or a planning illustration for a sponsor analysis that is not reported. The record also does not state whether any interim analyses took place, or describe a statistical analysis plan in enough detail to identify prespecified models or decision rules.

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("Elbasvir/Grazoprevir for HCV+ Kidney Transplant Re")
n      <- c(8)
events <- c(8)
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  Elbasvir/Grazoprevir for HCV+ Kidney Transplant Re  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7

11. Multiplicity, Missing Data and Analysis Populations

The record lists 2 outcome measures: the primary SVR12 endpoint and a secondary outcome assessing undetectable serum HCV RNA at multiple study days. It does not report analyses for these outcomes. How the study handled multiplicity across endpoints or repeated assessment times is not reported in the registry record. In general, testing multiple outcomes or time points can increase the chance of a chance finding if each is evaluated separately. Statistical approaches to address that issue depend on the study’s prespecified objectives and analysis plan, which are not described.

The registry record does not report a statistical analysis plan, a hierarchy for interpreting the listed endpoints, or any adjustment for multiple testing. It also does not state whether interim analyses took place. These details should not be inferred from the fact that repeated outcome times are listed or from the study’s completed status.

Missing-data handling is not reported in the registry record. The number of participants with available primary endpoint data, any reasons for missing assessments, and any method for handling missing outcomes are not stated. The analysis population is also not reported: the record does not specify whether the endpoint was analyzed among all enrolled participants, among those who received treatment, or under another definition. Without these details, a reader cannot determine how incomplete follow-up might affect the reported endpoint result. Since the result itself is not reported, there is no registry-based estimate to assess for sensitivity to missing data.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lymphocele (12.5%), renal vein thrombosis (12.5%), delayed graft function (12.5%), acute kidney injury (aki) (12.5%).

The adverse-event record lists 8 participants at risk for serious adverse events, with 4 affected, and 8 at risk for other adverse events, with 4 affected. It lists deaths as 0. These are participant counts in the treatment group, not a comparison between treatment strategies. The record also lists Lymphocele, Renal vein thrombosis, Delayed graft function, and Acute kidney injury (AKI) among the top serious adverse-event terms, each with 12.5%.

These figures should be read descriptively. The listing does not establish that elbasvir/grazoprevir caused an event, nor does it show whether an event was related to the transplant, the underlying condition, or another factor. The registry record does not provide event timing, duration, severity beyond the serious-event classification, outcomes, or attribution. It also does not clarify the relationship between the listed terms and the participant counts. The listed 0 deaths is a reported count, not a general estimate of mortality risk beyond this study group.

In general, adverse-event counts are most informative when read alongside definitions, follow-up duration, event-level details, and an appropriate comparison group. Those details are not reported in the registry record. The figures therefore describe reported events in the treated group but do not establish comparative safety or causation.

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

The registry record documents a proof-of-concept study of preemptive elbasvir/grazoprevir in recipients of kidneys from HCV-infected deceased donors. It specifies an endpoint based on undetectable HCV RNA at SVR12 and lists a secondary outcome with repeated viral RNA assessment times. Those details identify the question the study was intended to address and the way the primary virologic outcome was defined.

The record does not report the observed primary endpoint count, its denominator, or an estimate of uncertainty. It therefore does not show how many participants met the primary endpoint or how precisely any response frequency was estimated. The absence of a reported endpoint result should not be interpreted as a zero response, a failure, or evidence of success. It is a reporting gap in the registry record.

The design also sets limits on what a result could mean. With a single treatment group and no comparator, an observed outcome would describe the enrolled recipients but would not show how outcomes compare with an alternative approach. The open-label design and single-center description further define the setting in which the observations were collected. The record does not report additional analyses that could address these limitations.

The serious and other adverse-event counts provide descriptive safety information, including the listed serious-event terms and a death count of 0. They do not demonstrate that the intervention caused or prevented any event. Nor do they provide a comparison of safety with another transplant or treatment strategy.

Accordingly, the record can be used to understand the study’s design, intervention, endpoint, and some recorded adverse-event counts. It does not provide the primary outcome result needed to assess the observed virologic response, and it cannot support a comparative treatment conclusion.

14. Why This Trial Matters Statistically

This study raises a statistical question that is distinct from a conventional randomized comparison: whether a specified virologic outcome was observed in a group receiving preemptive treatment around transplantation. A proof-of-concept design can be useful for describing feasibility and observed outcomes in a defined setting. Its statistical interpretation nevertheless depends on clear endpoint reporting, an analysis denominator, and transparent treatment of uncertainty.

The study’s single-group structure makes that distinction especially important. A count of participants with undetectable HCV RNA could describe the group, but would not provide a direct estimate of how outcomes differ from a control strategy. Statistical language should not imply a comparative effect when the design has no comparator. The record’s allocation entry of NA and single-group model make this limitation explicit.

The registry record also illustrates why endpoint definitions and outcome reporting need to be read together. It defines SVR12 and gives a follow-up timeframe, but the observed primary endpoint count is not reported. Without that result, readers cannot assess the outcome’s magnitude or precision. Listing repeated secondary assessment times does not substitute for the measurements or their analysis.

Finally, planning illustrations and observed results answer different questions. Planning assumptions describe a hypothetical design calculation; they do not constitute observed power and do not repair the absence of a reported outcome. The record gives some assumptions for such an illustration but does not provide the trial’s own sample-size justification or numerical planning estimates. Separating design, analysis, and reporting information helps prevent an illustrative calculation from being mistaken for evidence about the trial’s outcome.

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 are specific to the information recorded for this study. Enrollment is listed as 8, and the design is single-group with allocation listed as NA. There is no concurrent control group, so the record cannot support a direct comparison with another treatment strategy. The study is open-label, and the registry does not describe masking of outcome assessment.

The primary endpoint is specified, but its observed count and analysis denominator are not reported in the registry record. This prevents assessment of the primary result, its precision, and the amount of missing outcome information. Results for the secondary outcome at the listed assessment times are also not reported. The record lists 0 analyses, and does not state the analysis population, missing-data approach, or handling of multiplicity.

The treatment duration is not fully consistent across the record: the arm description says daily treatment continued for 12 weeks, while the primary endpoint description refers to 12–16 weeks of treatment. The registry does not explain this difference. The record also does not provide detailed event-level information for adverse events, including timing and attribution. The listed adverse-event counts therefore have limited interpretive detail.

These limitations concern both study design and registry reporting. They do not establish that the underlying study lacked analyses or that outcomes were not collected; those matters are not reported in the registry record. They define what can be concluded from the posted record itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant — NCT02945150.
• Registry record last updated 2020-06-09; status last verified 2020-05.
• Results first posted 2020-02-26.
• 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 registry record describes a completed Phase 4, open-label, single-center, single-group proof-of-concept study sponsored by Massachusetts General Hospital. Enrollment is listed as 8. Participants received fixed-dose elbasvir 50mg / grazoprevir 100mg in the setting of kidney transplantation from an HCV-infected deceased donor to an HCV-naive recipient.

The primary endpoint is the number of participants with undetectable HCV RNA at SVR12. Its observed result is not reported in the registry record. The record lists a secondary viral RNA outcome at several study days and reports adverse-event counts, including 4 participants affected by serious adverse events and 0 deaths. It does not report comparative efficacy results, endpoint precision, analysis populations, or missing-data methods.