Valacyclovir in Neonatal Herpes Simplex Virus Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Valacyclovir in Neonatal Herpes Simplex Virus Disease (NCT04448392), a na phase 1 study. The primary outcome is Area Under the Curve Following Administration of Oral Valacyclovir Suspension 20 mg/kg Every 8 Hours.

2. Clinical Question

In general, a pharmacokinetic study characterizes how drug concentrations change over time in the body. It can describe exposure and related measures without establishing whether a treatment improves a clinical outcome. This study’s posted outcomes include pharmacokinetic measures and a creatinine-clearance measure; the registry record does not report a clinical efficacy endpoint. The question is therefore about drug exposure and safety in the studied group, not whether valacyclovir is better than another treatment.

3. Trial Design

The registry record identifies NCT04448392 as a phase 1 study titled “Valacyclovir in Neonatal Herpes Simplex Virus Disease.” It is recorded as completed, with an enrollment of 7, and as a single-group, open-label study. The sponsor is the University of Alabama at Birmingham. The listed study dates are 2021-07-01 for study start and 2024-07-24 for primary completion.

The brief description calls the study open-label and single center. Eligible infants with virologically confirmed neonatal herpes simplex virus disease were to receive valacyclovir after completing standard-of-care acyclovir treatment. The arm description specifies oral valacyclovir at 20 mg/kg every 8 hours for 2 (up to 7) days. The broader objective describes neonates 2-12 weeks of age and 34 weeks gestation or more.

There is no randomized control group in this design. The record lists allocation as not applicable and identifies a single group. A preceding acyclovir course provides context for a listed secondary pharmacokinetic comparison, but it does not make the study a randomized or concurrent comparison. Differences between measurements before and after treatment, if analyzed, would not by themselves separate treatment effects from other explanations such as changes over time or differences in measurement conditions.

The record lists 7 outcome measures and 0 analyses. It names the primary outcome as area under the curve following oral valacyclovir suspension. Secondary outcomes include measures following parenteral acyclovir and a comparison of area under the curve for intravenous acyclovir and oral valacyclovir. Outcome details include a specified collection window for the primary measure. The registry record does not report an analysis plan, a sample-size justification, interim analyses, or the results for these outcomes.

As general context, an early-phase pharmacokinetic study can characterize exposure and inform later research questions. Its single-group structure and enrollment describe the scope of this record; they do not establish comparative treatment effects.

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

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 Area Under the Curve Following Administration of Oral Valacyclovir Suspension 20 mg/kg Every 8 Hours, measured over Between Day 2 and Day 7 of valacyclovir administration: 0, 1-2, 3-5 hours..

The primary endpoint is the area under the curve following oral valacyclovir suspension at 20 mg/kg every 8 hours. The unit is mgxh/l, and the stated summary measure is the mean with standard deviation. The timeframe is between Day 2 and Day 7 of valacyclovir administration, with collection points listed as 0, 1-2, and 3-5 hours. The description says blood will be collected to determine the concentration of acyclovir, the metabolite of valacyclovir, and that the measure will include area under the curve.

In general, area under the concentration-time curve represents drug exposure across a measurement interval. It is used in pharmacokinetic research because it combines information about concentrations over time rather than relying on a single concentration reading. A mean describes the central value across participants, while standard deviation describes the spread of participant-level values around that mean.

The registry record does not report the observed mean, standard deviation, number of participants contributing endpoint data, or an inferential analysis. Thus, the endpoint definition and intended summary are available, but the size and precision of the observed exposure estimate cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that can be described are limited by what the registry record reports. It specifies a continuous primary endpoint summarized by a mean and standard deviation, but it does not report the endpoint result, a confidence interval, a p-value, or an analysis procedure. The record lists 0 analyses. The concepts below explain the named measures in general and should not be mistaken for a description of unreported methods used in this study.

What does area under the curve represent?

In general, a drug concentration-time curve plots concentration against time after dosing. The area under that curve summarizes exposure over the selected interval. Its interpretation depends on the sampling schedule, the units, and how the area is estimated. Here, the record identifies blood concentration of acyclovir, the metabolite of valacyclovir, and lists collection times of 0, 1-2, and 3-5 hours within the stated timeframe. It does not report the calculation method, individual concentration readings, or participant-level area-under-the-curve values.

Area under the curve is a pharmacokinetic measure, not a direct measure of clinical benefit. It may be useful for characterizing exposure and for comparing exposure measures in a defined setting. A difference in exposure alone would not establish a difference in clinical outcomes or establish that one treatment is preferable.

Why report a mean and standard deviation?

In general, the mean is the arithmetic average of observed values and provides a measure of their central location. The standard deviation describes the spread of individual observations around that average. Reporting both can help readers understand typical exposure and participant-to-participant variability. Neither statistic alone conveys the precision of the mean; a confidence interval can provide that inferential information when its method and analysis population are known.

The registry names mean and standard deviation as the summary format, but does not report their values. It also does not report a confidence interval or explain whether the distribution of the endpoint was assessed. No claim about normality, skewness, transformations, or alternative summaries can be made from the registry record.

What does a single-group design allow?

In general, a single-group study can describe measurements in participants who received the study intervention. It does not have a concurrent control group against which to distinguish an intervention-related change from other causes. This record describes valacyclovir after a standard acyclovir course and lists a secondary comparison of area under the curve for intravenous acyclovir and oral valacyclovir. The registry record does not explain the measurement or analysis structure for that comparison. It therefore does not support assumptions about pairing, adjustment, or the statistical test used.

Open-label describes the absence of masking in the listed design. It does not establish that a particular outcome was biased, but it means the record does not describe blinded treatment assignment. The outcome is a laboratory-based pharmacokinetic measure; details about laboratory blinding or assay procedures are not reported in the registry record.

How should planning calculations be read?

In general, a sample-size calculation describes the amount of information a proposed design is intended to collect under specified assumptions. It is not an observed treatment effect or a measure of what the completed study actually established. The planning assumptions associated with this record specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions describe a hypothetical two-arm planning illustration and do not match the recorded single-group design.

Any sample-size illustration is not observed power. Power is a design quantity calculated under assumed effects and variability; after a study is completed, it does not replace reporting the estimate and its uncertainty. The registry record does not report the study’s own sample-size justification, the assumed variability for its endpoint, or analysis details that would connect a planning calculation to the actual study.

What information is needed for a full statistical reading?

A full interpretation would require outcome values, the number of participants analyzed for each outcome, a description of missing measurements, and the methods used to summarize and compare observations. For inferential claims, it would also require the estimate and an appropriate measure of uncertainty. Those details are not reported in the registry record. The available design and endpoint descriptions identify the intended scientific question, but they do not establish the results or precision of the study’s pharmacokinetic estimates.

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("Neonatal HSV Disease Requiring Suppressive Therapy")
n   <- c(7)
m   <- c(28.8)
sp  <- c(16.8)
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  Neonatal HSV Disease Requiring Suppressive Therapy  7  28.800  16.800  13.263  44.337

11. Multiplicity, Missing Data and Analysis Populations

The record lists 7 outcome measures, including the primary area-under-the-curve endpoint and secondary pharmacokinetic and creatinine-clearance measures. It lists 0 analyses, and no multiplicity strategy is reported in the registry record. Multiplicity refers, in general, to the interpretive issue created when several outcomes or comparisons are assessed: the chance of obtaining at least one apparently notable result can depend on how many analyses are performed and how they are handled. No adjustment method, hierarchy among secondary outcomes, or prespecified testing strategy is reported.

The primary outcome is identified, but the record does not report a statistical analysis plan or results. It is therefore not possible to determine whether analyses followed a prespecified plan, how any multiple comparisons were handled, or whether outcome definitions changed. Interim analyses are not reported in the registry record.

Missing-data details are also absent. The enrollment is 7, but the number of participants with evaluable data for each outcome is not reported. The record does not state whether measurements were missing, how missing observations were handled, or whether any participants were excluded from particular analyses. Analysis populations—such as all enrolled participants or a subset with available measurements—are not described.

In general, these details matter because the number and characteristics of participants contributing to an estimate affect how it should be interpreted. Without outcome-specific denominators and missing-data methods, readers cannot assess whether the reported population, if results were available, would represent everyone enrolled. These gaps limit evaluation of both the statistical findings and the completeness of reporting.

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 0% reporting threshold.

The registry record lists one group, with 7 participants at risk for serious adverse events and 0 affected. It also lists 7 at risk for other adverse events and 0 affected, with 0 deaths. These are the posted counts for the group identified as neonatal herpes simplex disease requiring suppressive therapy.

In general, an at-risk count is the number of participants included in the record’s denominator for a safety outcome, while an affected count is the number recorded as having that outcome. The figures indicate that no serious adverse events, other adverse events, or deaths were recorded among the listed participants. They do not establish that the risk of an adverse event is absent. A small group can provide limited information about events that occur infrequently, and the registry record does not describe event definitions, severity grading, relatedness assessments, or the time period used for these safety counts.

The figures should also be kept separate from the pharmacokinetic outcomes. They do not provide the concentration data or answer the primary area-under-the-curve question. Further safety details, including descriptions of individual events or additional analyses, are not reported in the registry record.

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

The record describes an early-phase, open-label, single-group study of valacyclovir in neonates who had completed standard-of-care acyclovir treatment. Its primary outcome is a pharmacokinetic exposure measure based on blood concentrations of acyclovir, the metabolite of valacyclovir. The study enrolled 7 participants, and the registry record lists 0 analyses.

The endpoint definition identifies what investigators intended to measure, the summary format, and the collection timeframe. It does not provide the observed mean or standard deviation. The registry record therefore does not show the magnitude or variability of the measured exposure, nor does it provide an estimate’s precision. It also does not report the results of the secondary pharmacokinetic measures or the listed comparison with intravenous acyclovir.

In general, pharmacokinetic findings describe drug exposure under the study conditions. They are not, by themselves, evidence of clinical effectiveness. The single-group design also does not provide a concurrent randomized comparison that would support a causal claim about differences between treatments. No such claim can be drawn from the design description alone.

The safety counts record 0 serious adverse events, 0 other adverse events, and 0 deaths among 7 participants at risk. These counts describe what is recorded for this group; they do not show that adverse events are impossible or quantify risk precisely. The registry record does not report further safety analyses.

Accordingly, the record establishes the study’s question, design, enrollment, endpoint definition, and posted safety counts, but not its primary pharmacokinetic result. It does not support a conclusion about the size or precision of exposure, a treatment comparison, or clinical outcomes. Those limits reflect missing result and analysis information in the registry record, not a statistical finding of no effect.

14. Why This Trial Matters Statistically

This study is statistically useful as an example of a focused pharmacokinetic question in a specialized population. It identifies a primary exposure measure, a summary approach using mean and standard deviation, and a defined collection timeframe. Such details clarify what an analysis would need to estimate and which measurements would contribute to the endpoint.

The record also illustrates why design and analysis must be read together. A single-group study can describe observed values in participants who receive valacyclovir, but it does not supply a randomized concurrent comparison. Although the record lists a comparison involving intravenous acyclovir and oral valacyclovir, it does not report how that comparison was conducted or analyzed. The distinction prevents a pharmacokinetic description from being mistaken for evidence of comparative clinical effect.

Another important statistical issue is the gap between an outcome definition and an outcome result. The endpoint and planned summary are identifiable, but the mean, standard deviation, participant count for the endpoint, and uncertainty are not reported in the registry record. Without those elements, readers cannot assess the observed exposure or its precision. A completed status and an enrollment count do not replace outcome reporting.

The record’s safety counts also show why a zero count should be interpreted in the context of the number at risk and the study’s scope. The absence of recorded events among the listed participants is a descriptive result, not proof that an event cannot occur. These considerations are particularly important when interpreting small pharmacokinetic studies, whose primary purpose is characterization rather than broad comparative testing.

Finally, planning assumptions need to be distinguished from the design actually recorded. A two-arm planning illustration is not the same as an analysis of this single-group study and is not observed power. Clear reporting of estimates, uncertainty, analysis populations, missing data, and methods would be needed for a more complete statistical interpretation.

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.

The most important limitation for interpreting results is that the registry record does not report the primary endpoint value or any statistical analysis. The mean and standard deviation are named as the intended summaries, but their values are absent. The number of participants contributing to that endpoint, the variability of measurements, and the precision of any estimate are not reported in the registry record.

The study is recorded as single-group and open-label, with no concurrent randomized comparator. The record describes valacyclovir after completion of acyclovir treatment and lists a secondary comparison of exposure after intravenous acyclovir and oral valacyclovir. It does not provide details of that comparison or its results. Accordingly, the design description alone cannot establish a comparative treatment effect.

Enrollment was 7, while the brief description states that 6 (up to 10 infants) would be enrolled. The registry record does not explain this difference between the stated enrollment target description and the recorded enrollment, or report whether all enrolled participants contributed to each outcome. Outcome-specific denominators, missing-data handling, and analysis populations are not reported.

The record lists 7 outcome measures but 0 analyses. A statistical analysis plan, sample-size justification, interim analyses, multiplicity approach, and handling of missing data are not reported in the registry record. The planned sampling details are named, but assay procedures and the method for calculating area under the curve are not reported.

The safety results are limited to counts: 0 serious adverse events, 0 other adverse events, and 0 deaths among 7 participants at risk. Event definitions, detailed descriptions, and additional safety analyses are not reported. These limitations restrict interpretation of both the pharmacokinetic evidence and safety record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Valacyclovir in Neonatal Herpes Simplex Virus Disease — NCT04448392.
• Registry record last updated 2025-06-24; status last verified 2025-06.
• Results first posted 2025-06-24.
• 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.

19. Record Summary

NCT04448392 is a completed phase 1, open-label, single-group study sponsored by the University of Alabama at Birmingham. It enrolled 7 participants and is described as a single-center study of valacyclovir in neonates with neonatal herpes simplex virus disease after standard-of-care acyclovir treatment.

The primary outcome is area under the curve following oral valacyclovir suspension at 20 mg/kg every 8 hours, summarized as a mean and standard deviation. The registry record lists 7 outcome measures and 0 analyses, but does not report the primary outcome value or its statistical precision. It records 0 serious adverse events, 0 other adverse events, and 0 deaths among 7 participants at risk. The record does not report a randomized comparison, an analysis plan, outcome-specific analysis populations, or missing-data methods.