Herpes Simplex Type 1 Suppression in Hepatitis C: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Herpes Simplex Type 1 Suppression in Hepatitis C (NCT01580995), a randomized phase 2 study. The primary outcome is Change in HCV RNA Viral Load.

2. Clinical Question

3. Trial Design

NCT01580995, titled “Herpes Simplex Type 1 Suppression in Hepatitis C,” is a phase 2 randomized, double-masked, parallel-group trial. It enrolled 19 participants and is listed as completed. The registry records a start date of 2012-04 and primary completion in 2014-12. The study description says participation would take 16 weeks, with study visits every two weeks. The primary outcome, however, is specified at 12 weeks.

The target population was patients with chronic hepatitis C who had antibodies to HSV-1 but not HSV-2. Participants were assigned to valacyclovir or matching placebo. The recorded active regimen was valacyclovir 500 mg po bid, while placebo was taken twice daily. The description says participants and researchers would not know which medication was being received. The posted record does not give further details about how the random sequence was generated, how assignments were concealed, or how masking was maintained.

The primary outcome analysis population is described as patients who completed 12 weeks of follow-up. Posted arm summaries list 8 participants in the valacyclovir group and 7 in the placebo group. The registry does not report why the primary-outcome population differs from the enrollment figure, nor does it describe the follow-up status of participants absent from these arm summaries.

The sponsor is the VA Office of Research and Development. Study visits were planned at the G.V. Sonny Montgomery VA Medical Center in Jackson, Mississippi. The registry record does not report a sample-size justification or the planned statistical analysis in enough detail to determine how the study was designed to detect a clinically meaningful difference.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: patients who completed 12 weeks of follow up

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 Change in HCV RNA Viral Load, measured over Baseline, 12 weeks.

The primary endpoint is change in HCV RNA viral load, measured in log(IU/mL), from baseline to 12 weeks. HCV RNA is a measure of hepatitis C virus in the blood. The registry describes the endpoint as a comparison of change in viral load in the treatment group with change in the placebo group. The analysis population is patients who completed 12 weeks of follow-up.

Viral load is a continuous measure: it can take a range of values rather than representing a count of events or a yes-or-no outcome. The posted arm summaries identify the statistic as a mean and report standard deviations. A mean describes the central value of the observed measurements, while a standard deviation describes how spread out individual measurements are around that mean. General statistical interpretation: a mean alone does not show the full distribution of participant outcomes, and the standard deviation is not a confidence interval for the mean or for a treatment comparison.

The outcome is used to quantify a laboratory measure over the study period. It is not itself a report of symptoms, quality of life, or long-term clinical outcomes. The record gives the timing as baseline and 12 weeks but does not explain the detailed calculation used to derive each participant’s change score. It also does not report a clinically important threshold for interpreting the size of a change in log(IU/mL). Accordingly, the posted results describe the specified laboratory endpoint, not the broader course of hepatitis C or the effects of treatment beyond the observed follow-up.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is described as randomized, double-masked, and parallel-group. Randomization is intended, in general, to make assignment independent of participant characteristics, so that differences between groups can be interpreted as comparisons created by assignment rather than by deliberate selection. Masking is intended to reduce the influence of treatment knowledge on behavior, outcome assessment, and reporting. These are general purposes of the design; the registry record does not describe the randomization procedure, allocation concealment, or checks of masking.

A parallel-group design assigns participants to a treatment group that is compared with a separate control group over the study period. Here, the comparison was valacyclovir versus matching placebo. The posted primary outcome is change in a continuous laboratory measure between baseline and 12 weeks. General statistical explanation: for a continuous endpoint, a comparison can be framed as a difference between group means, with uncertainty estimated from the observed variability and the analysis model. The record reports each group’s mean and standard deviation, but it does not post a sponsor-reported mean difference or confidence interval. A recalculated comparison is also not available in the record’s results materials.

A standard deviation describes variation among observations within a group. It is not a measure of uncertainty in the estimated mean, and it does not directly express uncertainty about the difference between groups. A confidence interval is a range of values compatible with the data and an estimation procedure, under that procedure’s assumptions. Its width reflects statistical precision: a wider interval indicates greater uncertainty about the effect estimate. Since no treatment-effect confidence interval is reported and the continuous comparison is marked as not estimable for recalculation, the precision of the between-group effect cannot be assessed from a posted interval.

The registry lists Fisher Exact as the method for the reported analysis. General statistical explanation: Fisher’s exact test is commonly used for categorical data, where observations fall into discrete categories, and assesses evidence of association in a contingency table. The primary endpoint in this record is continuous, with a mean and standard deviation reported for each group. The registry does not explain how the Fisher Exact label relates to this endpoint, whether the continuous values were transformed into categories, or whether the method label is an error. Without those details, the p-value cannot be independently connected to a specified analysis of the continuous endpoint.

The p-value is 0.05. General statistical explanation: a p-value is calculated under a null hypothesis and the assumptions of a statistical test; it indicates how unusual data at least as incompatible with the null would be if that model were correct. It is not the probability that the null hypothesis is true, and it is not a measure of clinical importance. Interpretation also depends on knowing the test, the hypothesis, and the analysis plan. Although the registry’s planning assumptions mention a two-sided significance level of 0.05, the record does not state that this was the prespecified threshold for the sponsor’s analysis.

The sample-size assumptions describe planning illustrations based on fractions of an observed effect, equal allocation, a normal approximation, and a two-sided significance level of 0.05. Such illustrations estimate how many participants per arm might be required under stated assumptions. They are not observed trial results and do not establish the study’s original design rationale. The registry does not report the trial’s own sample-size justification, and no planning estimates should be mistaken for observed power.

Over-dispersion is a general concern when the observed variability exceeds what an analysis model assumes. If a model underestimates variability, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. The registry record does not report an over-dispersion assessment, and the posted summary statistics do not permit a conclusion about whether it affected the reported test. More broadly, the record does not give sufficient methodological detail to evaluate model assumptions or reproduce the sponsor’s inferential result.

For clinical interpretation, the distinction between a group summary and an effect estimate matters. The group means and standard deviations describe the observed values in each arm, but the treatment contrast needs its own estimate and uncertainty. The record does not provide that pair for the primary endpoint. Nor does it state whether baseline values were adjusted for, how missing follow-up was handled, or whether any covariates were included. These are not details that can be inferred from the labels for randomization or masking; they are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Valacyclovir", "Placebo")
n   <- c(8, 7)
m   <- c(0.24, 0.08)
sp  <- c(0.2, 0.01)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Valacyclovir  8  0.240  0.200  0.073  0.407
CARM  Placebo  7  0.080  0.010  0.071  0.089

11. Analyses Reported by the Sponsor

The registry reports a sponsor analysis using Fisher Exact, with p = 0.05. It does not report a sponsor-estimated treatment difference, a confidence interval, or the test statistic. The primary endpoint is continuous and the arm summaries are means with standard deviations, but the record does not explain how Fisher Exact was applied to this outcome. The p-value therefore cannot be fully interpreted as a reproducible analysis of the posted continuous measurements.

A re-calculation of the two-arm continuous comparison is not available: the record identifies the values needed for that comparison as missing or not estimable. The reported group summaries do not supply a sponsor-reported contrast, and no re-calculated contrast or confidence interval can be stated from the registry record. The discrepancy flag is false, so there is no identified conflict between a re-calculation and the sponsor result requiring the sponsor analysis to take precedence. In practical terms, the sponsor’s p-value is the only posted inferential result, while its method and the relationship to the endpoint remain insufficiently described for independent verification.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no posted secondary outcomes. It also lists one reported analysis. This limits what can be said about multiplicity: the posted record does not show a collection of multiple outcome tests, but it does not establish that the study involved no other analyses or decisions. The analysis plan, any prespecified hierarchy among outcomes, and any multiplicity adjustment are not reported in the registry record. It is therefore not possible to determine whether the reported p-value was selected from a wider set of analyses or whether its interpretation was adjusted for multiple testing.

The primary outcome population is described as patients who completed 12 weeks of follow-up. The posted arm summaries report 8 participants for valacyclovir and 7 for placebo, while enrollment is listed as 19. The record does not explain the difference between enrollment and the outcome-analysis population. It does not give participant-level reasons for missing outcome data, describe imputation, or report sensitivity analyses for missingness. The handling of participants who did not complete follow-up is therefore not reported in the registry record.

The record does not state whether the analysis followed intention-to-treat principles, whether participants were analyzed according to assigned treatment, or whether a per-protocol population was used. The available description ties the primary outcome to completion of follow-up but does not provide enough detail to classify the analysis population further. As a result, the extent to which randomization was preserved in the endpoint analysis cannot be determined from the registry entry alone.

General statistical explanation: missing outcomes can affect a comparison when the chance of having an observed outcome is related to treatment assignment or to the outcome itself. The direction and size of any resulting bias depend on the missing-data process and the analysis approach. Because reasons for non-completion and sensitivity analyses are absent, the robustness of the posted means and p-value to missingness cannot be assessed.

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 1% reporting threshold.

The safety results list 10 participants at risk for serious adverse events in the valacyclovir group and 9 in the placebo group. The recorded serious adverse event count is 0 in each group. The other adverse-event counts are also recorded as 0 in both groups, with 10 at risk in the valacyclovir group and 9 at risk in the placebo group. No serious adverse event terms are listed.

Deaths are not reported in the registry record. The zero counts describe what was posted for the listed groups; they do not establish that no adverse events of any kind occurred outside the categories or reporting captured in this entry. The record does not provide event definitions, a detailed adverse-event collection method, severity grades, or an explanation of how the safety populations relate to the primary-outcome populations.

These safety figures should be read as counts within the registry’s stated at-risk groups, not as proof of absence of risk. The study description gives a planned duration of 16 weeks, and the primary outcome was assessed at 12 weeks; the record does not provide longer-term safety follow-up. The safety data alone cannot characterize uncommon events or establish comparative safety beyond the observations recorded.

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

The results describe a randomized comparison of valacyclovir and placebo in patients with chronic hepatitis C who were HSV-1 seropositive and HSV-2 seronegative. The primary measure was change in HCV RNA viral load at 12 weeks among participants who completed follow-up. The posted means and standard deviations summarize the observed endpoint values by group, and the registry reports p = 0.05 from an analysis labeled Fisher Exact.

Those results do not provide a complete estimate of the treatment contrast. There is no reported between-group effect estimate or confidence interval, and a recalculated continuous comparison is not available. The method label is not explained in relation to the continuous endpoint. The reported p-value alone cannot establish the magnitude or precision of a difference, and cannot identify whether any observed change is clinically important. The registry does not report a threshold for clinical importance.

The entry also does not explain how missing follow-up data were handled or whether the analysis preserved the randomized groups. The outcome summaries are limited to participants who completed follow-up, and the reasons for the difference between enrollment and the outcome population are not reported. These features constrain how confidently the posted group summaries can be generalized to all randomized participants.

The trial’s question is specific to the study population, intervention, comparator, and follow-up described in the record. The findings do not establish effects on symptoms, long-term hepatitis C outcomes, or populations outside those described. The study summary explicitly says valacyclovir had not been approved to treat chronic hepatitis C. The record should therefore be read as a limited report of a laboratory endpoint and a sponsor p-value, not as a clinical recommendation or a definitive account of treatment benefit or harm.

15. Why This Trial Matters Statistically

This trial illustrates why the statistical description of an endpoint and its analysis needs to be internally clear. The primary outcome is a continuous change in HCV RNA viral load, and the registry posts group means and standard deviations. The reported analysis method is Fisher Exact, which is generally associated with categorical data. Because the registry does not explain the connection between the method and endpoint, readers cannot tell precisely what hypothesis was tested or reproduce the reported p-value.

It also illustrates the difference between describing each arm and estimating a treatment contrast. Arm summaries show the observed means and variability, but they are not a substitute for a between-group estimate with uncertainty. Without an effect estimate and confidence interval, readers cannot assess the precision or plausible range of the treatment comparison from the registry record. A p-value by itself does not fill that gap.

The population definition matters as well. The outcome is specified for participants who completed 12 weeks of follow-up, while enrollment is reported separately. Without an account of missing follow-up or the analysis population, readers cannot assess how the outcome summaries relate to the randomized groups. This is a general lesson in interpreting trial results: outcome availability and analysis choices are part of the statistical evidence, not administrative details.

Finally, planning illustrations based on an observed effect should not be confused with the trial’s original design justification or with observed power. The record describes assumptions for such illustrations but does not report the study’s own sample-size rationale. Keeping these distinctions clear helps prevent a sparse registry result from being read as more conclusive or precise than the posted information supports.

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.

The registry record leaves important details of the primary analysis unclear. It reports means and standard deviations for a continuous endpoint but identifies Fisher Exact as the analysis method. It does not explain how this test was used, state the exact statistical hypothesis, or provide a test statistic. The sponsor’s p-value is therefore difficult to evaluate in relation to the endpoint definition.

No sponsor-reported between-group estimate or confidence interval is posted, and no recalculation is available for the continuous comparison. The posted arm summaries cannot establish the precision of the treatment contrast. The record also does not report a clinically meaningful threshold for change in HCV RNA, so the clinical relevance of the observed means cannot be determined from the entry.

The outcome population is limited to participants who completed 12 weeks of follow-up. The registry does not report reasons for missing outcomes, whether analysis followed randomized assignment, or whether sensitivity analyses were conducted. Nor does it provide detailed baseline characteristics that would help readers assess the enrolled population and the distribution of baseline viral load.

Information about trial conduct is also limited. Although the study is described as randomized and double-masked, the sequence-generation and allocation-concealment methods are not reported. The protocol’s statistical analysis plan, sample-size justification, interim analyses, and any multiplicity procedures are not reported in the registry record. Safety reporting is limited to the posted counts, with no serious-event terms and no death counts reported. These gaps constrain independent assessment of the result and its generalizability.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Herpes Simplex Type 1 Suppression in Hepatitis C — NCT01580995.
• Registry record last updated 2016-09-21; status last verified 2016-08.
• Results first posted 2016-09-21.
• 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

NCT01580995 is a completed phase 2, randomized, double-masked, parallel-group study sponsored by the VA Office of Research and Development. It enrolled 19 participants with chronic hepatitis C who had antibodies to HSV-1 and not HSV-2. The intervention was valacyclovir 500 mg po bid; the comparator was matching placebo taken twice daily.

The primary endpoint was change in HCV RNA viral load, measured in log(IU/mL), from baseline to 12 weeks among patients completing follow-up. The registry posts group means and standard deviations and reports a Fisher Exact p-value of 0.05. It does not post a treatment-effect estimate or confidence interval, and the stated analysis method is not explained in relation to the continuous endpoint. Missing-data handling and the trial’s own sample-size rationale are not reported in the registry record.