Maribavir Versus Oral Ganciclovir For The Prevention of Cytomegalovirus (CMV) Disease in Liver Transplant Recipients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Maribavir Versus Oral Ganciclovir For The Prevention of Cytomegalovirus (CMV) Disease in Liver Transplant Recipients (NCT00497796), a randomized phase 3 study. The primary outcome is Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group Phase 3 study comparing prophylactic maribavir with oral ganciclovir in recipients of orthotopic liver transplants. The study was listed as completed, with enrollment of 307. The registry lists triple masking; the public record does not identify which roles were masked in the masking designation.

The interventions were maribavir 100 mg BID and ganciclovir 1000 mg TID. The brief summary describes administration for up to 14 weeks. The primary outcome was assessed within 6 months post-transplantation, and the primary analysis population was modified Intent-to-Treat. That population required randomization, at least one dose of study drug, and participation for at least 14 weeks or the potential to receive 14 weeks of therapy by 12-Feb-2009.

The primary endpoint was not simply a laboratory-positive CMV test. It concerned CMV disease adjudicated by an independent, blinded Endpoint Committee. Secondary outcomes covered CMV infection or disease, timing of onset, graft-related outcomes, and acute graft rejection. The registry lists 13 outcome measures and 14 analyses, with 12 secondary outcomes posted.

The registry lists the study start as 2007-07-23 and primary completion as 2009-09-14. It does not report the original sample-size justification, the planned statistical analysis details, or the allocation ratio. Although the design is described as randomized, parallel, and triple-masked, further procedural details are 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The modified Intent-to-Treat (ITT-M) population, defined as all randomized subjects who received at least one dose of study drug and had participated in the study for at least 14 weeks or had the potential to receive 14 weeks of therapy by 12-Feb-2009.

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: The Intent-to-Treat Safety (ITT-S) population, defined as all randomized subjects who received at least one dose of study drug, regardless of whether they had any post-baseline evaluations.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation, measured over 6 months post-transplant.

The primary endpoint counted participants with Endpoint Committee-confirmed CMV disease within 6 months post-transplantation. The registry says investigator-determined, protocol-defined cases were adjudicated by an independent, blinded Endpoint Committee. The endpoint included symptomatic CMV infection or CMV organ disease.

For symptomatic CMV infection, the registry definition required a positive central laboratory CMV assay along with fever on repeated occasions and at least one listed clinical or laboratory feature. The listed features included new or increased malaise, repeated measurements of leucopenia, atypical lymphocytosis, or thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002; further detail about that definition is not reported in the registry record.

As a general statistical point, an adjudicated clinical endpoint can apply consistent criteria across groups and reduce reliance on an investigator’s unreviewed classification. The endpoint is therefore a count of participants meeting the specified disease definition, not a measure of all CMV laboratory detection. Its time window also matters: the primary question concerns disease occurring within 6 months after transplantation, while some secondary outcomes use other windows.

7. Results Posted in the Registry

• Ganciclovir 1000 mg TID: 8.3% (10/120) versus 12.4% (14/113) on control; risk difference -4.1 percentage points (95% CI -11.9 to 3.8), risk ratio 0.67 (0.31–1.45); unadjusted two-proportion z-test p = 0.309.

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.

Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Maribavir 100 mg BID vs Ganciclovir 1000 mg TID: hazard ratio 2.25 (95% CI 1.62–3.14), reported p < 0.001 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically higher for Maribavir 100 mg BID vs Ganciclovir 1000 mg TID than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ganciclovir 1000 mg TID: 0.0% (0/120) versus 8.8% (10/113) on control; risk difference -8.8 percentage points (95% CI -14.1 to -3.6); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Ganciclovir 1000 mg TID than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants Who Died Within 6 Months Post-Transplantation

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ganciclovir 1000 mg TID: 3.8% (6/156) versus 6.1% (9/147) on control; risk difference -2.3 percentage points (95% CI -7.2 to 2.6), risk ratio 0.63 (0.23–1.72); unadjusted two-proportion z-test p = 0.361.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ganciclovir 1000 mg TID and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the primary question to different CMV definitions and follow-up windows, including CMV infection or Endpoint Committee-confirmed disease, onset timing, investigator-determined disease, and disease within 100 days. Other outcomes concern retransplantation, graft failure-related death, acute graft rejection, and death. They address related but distinct aspects of post-transplant outcomes rather than serving as interchangeable measures of the primary endpoint.

The overall pattern is not uniform across these outcome types. The time-to-onset result and the 100-day Endpoint Committee-confirmed disease result have reported analyses that favor ganciclovir in the direction of fewer or later events, while the primary endpoint’s unadjusted interval includes no difference. The secondary outcomes also include broader infection measures and graft-related outcomes, for which findings cannot be assumed to mirror the primary endpoint. The registry lists 12 secondary outcomes as posted, but not every listed outcome has a corresponding detailed result in the record summarized for this analysis.

As a general statistical point, examining many outcomes creates more opportunities for apparently notable results to arise by chance. Unless multiplicity is addressed, a secondary p-value should be treated as exploratory rather than as independent confirmation of the primary result. The registry does not report a multiplicity-adjustment strategy. Secondary endpoints can help describe the range of observed outcomes and generate questions for further study, but their evidential weight depends on their prespecification, analysis methods, missing-data handling, and relationship to the primary endpoint. Those details are not fully reported in the registry record.

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

• Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation
• Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation
• Number of Participants With Investigator-determined CMV Disease
• Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation
• Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation
• Number of Participants With Retransplantation
• Number of Participants With Graft Failure Related Death
• Number of Participants With Acute Graft Rejection

9. Statistical Interpretation

10. Statistical Methods Explained

What does a risk difference represent?

As a general statistical explanation, a risk difference compares the proportion of participants with an event in one group with the proportion in another. It is expressed on the probability scale, so a value of zero represents equal observed risks. The recalculated risk difference for the primary endpoint is -0.041 when the order is ganciclovir minus maribavir. Its negative sign means the observed event proportion was lower in the ganciclovir group. The estimate is unadjusted and is calculated from the posted summary counts.

The registry reports a rate difference of 0.041 in the opposite group order, maribavir then ganciclovir. The sign change is a consequence of reversing the order of subtraction, not a different direction of the underlying comparison. The registry’s reported result and the recalculation should not be treated as interchangeable methods: the former is the sponsor’s analysis, while the latter is a simple unadjusted calculation from the posted group summaries.

What does an odds ratio represent?

As a general statistical explanation, an odds ratio compares event odds between groups. An odds ratio of one is the null value, indicating equal odds. The sponsor reports an odds ratio of 1.586 from a Cochran-Mantel-Haenszel analysis, with a 95% confidence interval from 0.682 to 3.690 and p = 0.275. The registry presents this analysis with maribavir first and ganciclovir second. Because the interval includes one, it does not establish a difference in odds at the stated confidence level. Odds ratios and risk differences use different scales and need not have matching numerical magnitudes.

The Cochran-Mantel-Haenszel method is a method for estimating an association across strata. The registry names the method, but does not report the stratification variables or further details of its implementation. Those details should not be inferred from the method name alone.

How should the time-to-event result be read?

The secondary time-to-onset analysis reports a median time of 45.0 days for maribavir and 127.0 days for ganciclovir. The registry reports an adjusted hazard ratio of 2.25 for maribavir versus ganciclovir, with a 95% confidence interval from 1.62 to 3.14 and p < 0.001, using a Log Rank method. In this comparison, the event is onset of CMV infection or Endpoint Committee-confirmed CMV disease. A hazard ratio concerns the relative event rate over follow-up, not a direct comparison of medians or a risk difference at a single time point.

As a general statistical point, time-to-event methods can account for differing follow-up times and censoring, but their interpretation depends on the analysis and assumptions. The registry does not report further details of censoring or the adjustment variables for this analysis. The reported hazard ratio should therefore be described as the registry’s adjusted estimate rather than as a result that can be reconstructed from the posted medians.

Why distinguish reported analyses from recalculations?

The registry contains sponsor-reported analyses as well as group counts from which simple unadjusted comparisons can be recalculated. A recalculation using summary counts cannot reproduce an adjusted or stratified analysis without its underlying data and specifications. The primary recalculation is useful for describing the posted counts and their unadjusted uncertainty, but it does not replace the sponsor’s own analysis. When the sponsor’s reported analysis and a recalculation differ, the sponsor’s analysis takes precedence as the trial’s reported analysis.

As a general statistical point, a p-value describes how compatible the observed data are with a specified null hypothesis under a statistical model. It does not state the probability that the null hypothesis is true, nor does it measure clinical importance. Confidence intervals give a range of estimates compatible with the data and model at the stated confidence level. Both should be read alongside the endpoint definition, analysis population, and limitations of the available record.

11. Confidence Intervals and Precision

The recalculated risk difference for the primary endpoint is -0.041, with a 95% confidence interval from -0.119 to 0.038. This interval includes zero, so the unadjusted summary data do not locate the risk difference precisely enough to rule out no difference at that confidence level. It also spans values on both sides of zero, leaving uncertainty about the direction and size of the underlying difference.

The sponsor’s reported rate difference is 0.041, with a 95% confidence interval from -0.038 to 0.119, in the maribavir-minus-ganciclovir order. The sponsor’s odds ratio is 1.586, with a 95% confidence interval from 0.682 to 3.690. The risk-difference interval includes its null value of zero, and the odds-ratio interval includes its null value of one. These intervals do not establish a primary-endpoint difference in the reported analyses.

As a general statistical point, a confidence interval is a range of estimates compatible with the observed data under the analysis model. It is not a guarantee that the true effect lies in the interval, and it does not assign probabilities to individual values within the range. A wide interval signals limited precision relative to the range of effects it permits; it does not by itself identify why precision is limited.

For the secondary time-to-onset analysis, the reported adjusted hazard ratio is 2.25, with a 95% confidence interval from 1.62 to 3.14. The interval excludes one, the null value for a hazard ratio. That result concerns time to the secondary event and does not change the uncertainty attached to the primary endpoint estimate. Differences in endpoint, analysis population, and statistical method mean the confidence intervals answer different questions.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations are not the trial’s original design calculations. The original sample-size assumptions are not reported in the registry record. For binary outcomes, the figures are participants per arm; for time-to-event outcomes, the figures are total events. The primary endpoint planning values therefore refer to participants per arm, while the time-to-onset planning values refer to total events.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row uses the stated fraction of the observed effect as the effect to detect. The 80% power column gives the illustrated number of participants per arm, or total events for a time-to-event calculation, for an 80% chance of detecting that assumed effect under those assumptions. The 90% power column gives the corresponding requirement for a 90% chance.

Smaller effects require more information to detect under the same assumptions. Thus the planning rows for a smaller fraction of the observed effect require more participants or events than the rows based on the full observed effect. These figures are planning illustrations, not a description of the enrollment target or analysis plan that governed the completed study.

These calculations are not observed power. They do not measure the probability that the completed trial detected an effect, and they should not be used to reinterpret the primary confidence interval. The trial’s own sample-size rationale, target effect, and original planning assumptions are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.124; treatment proportion p₁ = 0.083; average p̄ = 0.104.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4310 = 0.8447.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4300 = 0.3619.
4. n = (0.8447 + 0.3619)² / (-0.0406)² = 885.0, rounded up to 886 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.123893805309735                          # control proportion
p1 <- 0.0833333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(497796)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 886 (80% power), 1,185 (90% power)
 75% of observed effect: n per arm = 1,643 (80% power), 2,198 (90% power)
 50% of observed effect: n per arm = 3,847 (80% power), 5,150 (90% power)
power.prop.test: 885 
Simulated power at n = 886 per arm: 0.806 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s primary-endpoint analyses include a reported rate difference and a Cochran-Mantel-Haenszel odds ratio. The rate difference is 0.041, with a 95% confidence interval from -0.038 to 0.119, for maribavir minus ganciclovir. The odds ratio is 1.586, with a 95% confidence interval from 0.682 to 3.690 and p = 0.275. Both reported intervals include their respective null values.

The recalculation from the posted counts gives a risk difference of -0.041, with a 95% confidence interval from -0.119 to 0.038, for ganciclovir minus maribavir. Its sign is reversed because the subtraction order is reversed. It is an unadjusted calculation, whereas the registry identifies the odds-ratio analysis as Cochran-Mantel-Haenszel. A direct comparison of point estimates must account for both the change of direction and the difference in statistical measure.

The sponsor’s own analysis takes precedence over a simple recalculation when describing the trial’s reported result. The recalculation is a supplementary check based on posted summary counts; it cannot reproduce analysis details that are not reported. The registry labels the reported rate-difference analysis as a legacy non-inferiority or equivalence analysis, but does not report a margin in the information available for this endpoint. A non-significant result in the superiority analysis, or an interval containing the null, should not be interpreted as proof of equivalence.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 14 analyses, with 12 secondary outcomes posted. Multiple endpoints and analyses create a multiplicity issue: when many statistical tests are conducted, the chance of at least one small p-value can increase even if there is no underlying effect across the outcomes. As a general statistical point, a prespecified strategy can control or describe that issue, but the strategy used for this trial is not reported in the registry record.

The primary population is described as modified Intent-to-Treat. It included randomized subjects who received at least one dose of study drug and participated for at least 14 weeks or had the potential to receive 14 weeks of therapy by 12-Feb-2009. This definition differs from a population that automatically includes every randomized participant regardless of treatment exposure or follow-up eligibility. The primary group sizes reported for the endpoint are 113 and 120.

The registry does not report the extent or reasons for missing outcome data, the method used to handle missing data, or sensitivity analyses for missingness. It also does not report a detailed protocol for treatment of participants who discontinued or had incomplete follow-up. These omissions limit assessment of whether missingness could have influenced the endpoint comparisons.

The registry identifies some methods, including Cochran-Mantel-Haenszel for the primary odds ratio and Log Rank for the time-to-onset analysis, but does not provide a complete statistical analysis plan. The original sample-size justification, interim-analysis plan, multiplicity procedure, and detailed allocation procedure are not reported in the registry record. Their absence from the record is not evidence that a procedure was or was not used; it means that the available information does not permit those design and analysis choices to be evaluated.

16. 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: cytomegalovirus infection (8.2%), liver transplant rejection (7.7%), hepatic enzyme increased (5.4%), pyrexia (4.5%), bile duct stenosis (2.7%).

The registry reports serious adverse events for 71 of 147 participants in the maribavir group and 76 of 156 in the ganciclovir group. Other adverse events were reported for 127 of 147 and 140 of 156, respectively. These are counts of participants with events in the listed safety groups; they are not the primary efficacy endpoint and should be interpreted separately from the CMV disease analysis.

The registry lists Cytomegalovirus Infection at 8.2%, Liver Transplant Rejection at 7.7%, Hepatic Enzyme Increased at 5.4%, Pyrexia at 4.5%, Bile Duct Stenosis at 2.7%, and Post Procedural Bile Leak at 2.7% among the top serious terms. The listing does not give arm-specific figures for those terms in the information, so they cannot be used to compare the groups term by term.

As a general statistical point, adverse-event counts describe observed events over the recorded safety follow-up; interpretation also depends on event definitions, exposure, follow-up, and handling of repeated events. Further details on those matters are not reported in the registry record. The serious-event figures alone do not establish a comparative safety advantage.

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

The primary endpoint counts participants with Endpoint Committee-confirmed CMV disease within 6 months after transplantation. The observed counts were 14 in the maribavir group and 10 in the ganciclovir group. The unadjusted risk-difference interval includes zero, and the sponsor’s reported primary analyses also have confidence intervals that include their null values. These results leave uncertainty about the size and direction of a primary-endpoint difference.

That uncertainty does not establish that the groups are equivalent, nor does it prove that their outcomes are identical. A conclusion of equivalence or non-inferiority requires an appropriate prespecified margin and analysis. Although the registry labels one reported analysis as a non-inferiority or equivalence legacy analysis, the margin and supporting design details are not reported in the registry record.

The secondary time-to-onset and 100-day disease analyses address different outcomes and time windows. They should not be substituted for the primary endpoint or treated as though they resolve its uncertainty. Likewise, the reported adverse-event counts describe safety observations and do not by themselves establish the overall balance of benefits and harms.

As a general statistical point, results apply most directly to the population, treatment regimens, endpoint definitions, and follow-up described in the trial record. They do not automatically answer questions about other regimens, populations, or periods. The record supports a description of the observed results and their statistical uncertainty; it does not, by itself, justify medical advice or a claim that either treatment works or does not work.

18. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition matters. The primary outcome was not all detection of CMV; it was disease determined under protocol criteria and reviewed by an independent, blinded Endpoint Committee. That distinction affects what the event count represents and what clinical question the comparison can address.

It also illustrates the importance of separating a point estimate from its precision. The primary counts differ, but the recalculated confidence interval includes zero. Reporting the observed direction without the interval could overstate what the data establish. Conversely, a non-significant p-value is not evidence that the groups are identical.

The registry also places several kinds of analyses side by side: an unadjusted recalculation, a sponsor-reported rate difference, a Cochran-Mantel-Haenszel odds ratio, and a Log Rank time-to-event analysis for a secondary outcome. These measures answer different statistical questions and may use different analysis details. Reading them requires attention to group ordering, endpoint, follow-up window, and method rather than comparing their numerical values as if they were on one scale.

Finally, the record demonstrates how incomplete reporting constrains evaluation. The primary analysis population and named methods are available, but original sample-size assumptions, multiplicity handling, and missing-data procedures are not reported. Statistical interpretation therefore includes not only estimates and intervals but also a careful account of what the record does not establish.

19. 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 primary endpoint analysis is reported for a modified Intent-to-Treat population rather than a population defined solely by randomization. The eligibility definition required at least one dose and a specified period of participation or potential treatment. The record does not describe how many randomized participants were excluded from this analysis or the reasons for any exclusions.

The registry does not report missing outcome counts, reasons for missingness, imputation procedures, or sensitivity analyses. Without those details, the potential influence of incomplete follow-up on the endpoint estimates cannot be assessed from the record. The original sample-size justification and detailed analysis plan are also not reported, including the non-inferiority margin associated with the legacy analysis label.

The recalculated primary comparison uses posted summary counts and is unadjusted. It cannot account for any stratification, covariate adjustment, or other features not represented in those counts. The sponsor’s reported analysis should be used as the trial’s own result, while recognizing that the registry does not provide all details needed to reproduce it.

Several secondary outcomes involve distinct definitions and time windows, and the registry does not report a multiplicity strategy. Their results therefore require caution, particularly when considered alongside the primary endpoint. Safety reporting includes group-level serious and other adverse-event counts and a list of top serious terms, but arm-specific figures for the listed terms and additional exposure details are not reported in the registry record.

The record describes randomization and triple masking but provides limited procedural detail. The masking roles, allocation procedure, and full conduct of follow-up are not reported. These reporting limits constrain assessment of bias and precision; they do not establish that any particular bias occurred.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Maribavir Versus Oral Ganciclovir For The Prevention of Cytomegalovirus (CMV) Disease in Liver Transplant Recipients — NCT00497796.
• Registry record last updated 2021-06-11; status last verified 2021-06.
• Results first posted 2015-06-04.
• 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.

23. Record Summary

The registry describes a completed, randomized, parallel-group Phase 3 study of oral maribavir versus oral ganciclovir for prevention of CMV disease in liver transplant recipients. Enrollment was 307, and the study was listed as triple-masked. The primary endpoint was Endpoint Committee-confirmed CMV disease within 6 months post-transplantation in a modified Intent-to-Treat population.

The posted primary counts were 14 of 113 for maribavir and 10 of 120 for ganciclovir. The recalculated unadjusted risk-difference interval includes zero; the sponsor’s reported primary analyses also have intervals including their null values. Secondary outcomes address other CMV definitions, timing, and post-transplant outcomes. Important design and analysis details, including missing-data and multiplicity procedures and the original sample-size rationale, are not reported in the registry record.