Safety and Efficacy Study of Posaconazole vs. Fluconazole for Prevention of Invasive Fungal Infection (P05387 AM1)(COMPLETED): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Posaconazole vs. Fluconazole for Prevention of Invasive Fungal Infection (P05387 AM1)(COMPLETED) (NCT00811928), a randomized phase 3 study. The primary outcome is Number of Participants With Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, open-label, parallel-group, multicenter study comparing posaconazole with fluconazole. The registry reports an enrollment of 252 participants and lists the study as completed. The start is recorded as 2008-11 and primary completion as 2010-05. Further details about the sites are not reported in the registry record.

Participants were assigned to one of the two study drugs. The study was open label, meaning masking was not used according to the registry record. The posaconazole regimen was an oral suspension of 200 mg TID, while the fluconazole regimen was a 400 mg capsule QD. The registry identifies leukopenia as the condition and characterizes the target group as high-risk leukopenic patients. It does not provide more detailed eligibility criteria in the record summarized for this analysis.

The primary outcome was the number of participants with a proven or probable IFI during treatment, with assessment extending to the last dosage date and up to 12 weeks (84 days) plus 7 days. The primary analysis population was the full analysis set: randomized participants who received at least one dose and had at least one post-treatment follow-up datum for the primary efficacy variable. Each group had 117 participants in that analysis. The registry does not report the trial’s original sample-size justification, its detailed statistical analysis plan, or the reasons that the full analysis set differs in size from the overall enrollment.

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 full analysis set (FAS) included all of those randomized participants who received at least one dose of study drug, and had at least one post-treatment follow-up data of primary efficacy variable.

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 Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period, measured over Up to 12 Weeks (84 days) plus 7 days.

The primary endpoint counts participants who developed a proven or probable invasive fungal infection during the treatment period. The registry defines the assessment window as up to 12 weeks (84 days) plus 7 days, from randomization to the last dosage date. Its description says IFI diagnosis criteria may include persistent fever, failure of appropriate broad-spectrum antibiotic treatment with lower respiratory tract infection symptoms, and microbiological criteria accompanied by corresponding clinical signs and symptoms.

This endpoint is used to summarize whether an infection occurred during the specified period. A participant contributes to the event count if a qualifying diagnosis is recorded; the endpoint does not describe how quickly an event occurred or how long it lasted. Those questions are addressed by separate outcomes in the registry, including time to first proven or probable IFI. Counts are straightforward to interpret, but they do not preserve the timing of events or account for differing follow-up time in the way a time-to-event analysis can.

The primary analysis population was the full analysis set, requiring randomization, at least one dose, and at least one post-treatment follow-up datum for this outcome. The registry’s definition therefore excludes randomized participants who did not meet those analysis-population requirements. Further detail about the handling of participants with incomplete endpoint information is not reported in the registry record.

7. Results Posted in the Registry

• Fluconazole: 9.4% (11/117) versus 3.4% (4/117) on control; risk difference 6.0 percentage points (95% CI -0.2 to 12.2), risk ratio 2.75 (0.90–8.39); unadjusted two-proportion z-test p = 0.062.

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.

Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization

• 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:
  • Fluconazole: 13.7% (16/117) versus 4.3% (5/117) on control; risk difference 9.4 percentage points (95% CI 2.2 to 16.6), risk ratio 3.20 (1.21–8.45); unadjusted two-proportion z-test p = 0.012.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Fluconazole than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants With Clinical Failure During Treatment

• 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:
  • Fluconazole: 43.6% (51/117) versus 31.6% (37/117) on control; risk difference 12.0 percentage points (95% CI -0.4 to 24.3), risk ratio 1.38 (0.98–1.93); unadjusted two-proportion z-test p = 0.059.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Fluconazole and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants in Whom All-cause Mortality Occurred Within 100 Days From Randomization

• 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:
  • Fluconazole: 6.8% (8/117) versus 2.6% (3/117) on control; risk difference 4.3 percentage points (95% CI -1.1 to 9.7), risk ratio 2.67 (0.73–9.80); unadjusted two-proportion z-test p = 0.123.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Fluconazole and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the picture beyond the primary treatment-period endpoint. The registry lists outcomes covering IFI within 100 days, time to first IFI, time to first systemic intravenous antifungal therapy, clinical failure during treatment, all-cause mortality within 100 days, and mortality considered related to fungal infection within 100 days. Numerical results are posted for some of these outcomes, but not all listed outcomes have detailed numerical results in the registry record.

Across the outcomes with detailed counts, the observed group differences generally have more events in the fluconazole group. This pattern is directionally consistent with the primary endpoint’s observed counts, but the outcomes are not interchangeable: their definitions, follow-up windows, and event types differ. The secondary results therefore offer context rather than an independent replication of the primary comparison. In particular, the 100-day IFI outcome extends beyond the primary treatment-period window, while clinical failure and mortality capture different events.

Unadjusted secondary comparisons carry less weight when several outcomes are examined. General statistical explanation: when many hypotheses are tested, the chance of at least one apparently noteworthy result arising by chance increases unless the analysis accounts for multiplicity or uses a prespecified hierarchy. The registry does not report a multiplicity adjustment or a hierarchical testing plan. Secondary estimates should therefore be interpreted as exploratory descriptions of the posted data, not as separate confirmatory findings. Missing numerical results for listed outcomes further limit any overall synthesis of the secondary evidence.

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

• Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization
• Time From Randomization to the First Onset of Proven or Probable IFI
• Time From Randomization to Administration of First Systemic Antifungal Intravenous (IV) Therapy
• Number of Participants With Clinical Failure During Treatment
• Number of Participants in Whom All-cause Mortality Occurred Within 100 Days From Randomization
• Number of Participants in Whom Mortality is Unlikely, Possibly, and Probably Related to Fungal Infection Occurred Within 100 Days From Randomization

9. Statistical Interpretation

10. Statistical Methods Explained

The central comparison is between the proportion of participants with a recorded primary endpoint event in each randomized group. General statistical explanation: a risk difference subtracts one group’s event proportion from the other’s. The sign depends on which group is placed first. The recalculated estimate uses fluconazole relative to posaconazole, whereas the sponsor analysis reports the difference in the reverse direction. The underlying counts are the same, but the direction of the contrast changes how a positive or negative estimate is read.

What does the risk difference describe?

The risk difference is an absolute comparison on the event-proportion scale. It indicates how far apart the observed event proportions are, rather than expressing a relative change. In this analysis, the recalculated risk difference is 0.060. Its confidence interval runs from -0.003 to 0.122. Because the interval crosses zero, it includes values corresponding to no difference as well as values on either side of zero. That uncertainty matters: the point estimate alone does not show how stable the comparison may be across plausible values.

The registry also includes relative measures, including a risk ratio and an odds ratio. General statistical explanation: relative measures compare event frequency by division, while an odds ratio compares event odds. They use different scales and should not be treated as interchangeable with an absolute risk difference. Rare events can make relative estimates especially sensitive to small changes in the event counts. The main interpretation therefore keeps attention on the actual counts, the absolute comparison, and the confidence interval.

What does the p-value add?

The recalculated unadjusted p-value is 0.062. General statistical explanation: a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be, if that null hypothesis and the statistical model were correct. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. It also does not summarize the full range of uncertainty; the confidence interval is useful for that. The registry’s own primary analysis does not include a p-value in the posted analysis record.

The label attached to the sponsor analysis is non-inferiority or equivalence. General statistical explanation: a non-inferiority analysis asks whether the data exclude a loss larger than a prespecified acceptable margin; an equivalence analysis asks whether the data lie within prespecified bounds in both directions. The margin, direction, and formal decision criteria are essential to those interpretations. They are not reported in the registry record, so the sponsor’s label and confidence interval cannot independently establish a non-inferiority or equivalence conclusion.

What is meant by an unadjusted recalculation?

The recalculation uses the posted group counts and is not presented as a substitute for the sponsor’s analysis. General statistical explanation: an unadjusted comparison does not account for other covariates or design features beyond the group contrast in the calculation. Adjustment can matter if the analysis plan prespecifies stratification, covariate adjustment, or another model. The method used for the sponsor’s primary comparison is not reported in the registry record, so the recalculation is best read as a transparent descriptive comparison rather than as a reconstruction of the full trial analysis.

Participant counts are the natural unit for this binary endpoint: each participant either had a qualifying event recorded or did not. General statistical explanation: time-to-event analyses instead use the timing of events and can incorporate censoring, where a participant’s event status is not observed throughout the whole period. The registry lists time-to-first-IFI and time-to-first-systemic-antifungal-therapy outcomes, but their numerical results and analysis methods are not reported in the detailed results available in the record.

Finally, interpretation depends on the analysis population and endpoint ascertainment. The full analysis set includes randomized participants who received at least one dose and had at least one post-treatment follow-up datum for the primary variable. The registry does not describe imputation, sensitivity analyses for missing outcomes, or a per-protocol analysis. Those omissions limit assessment of how robust the primary comparison is to analysis-population choices and incomplete follow-up.

11. Confidence Intervals and Precision

The recalculated primary risk difference is 0.060, with a 95% confidence interval from -0.003 to 0.122. The interval is broad enough to include zero and estimates on either side of zero. Thus the data are compatible with no difference under this unadjusted comparison, as well as with a positive risk difference when the contrast is expressed as fluconazole relative to posaconazole. The interval’s upper end also allows a larger difference than the point estimate. The estimate should therefore be read together with its uncertainty rather than as a precise fixed effect.

General statistical explanation: a confidence interval is a range produced by a method designed to have a stated long-run coverage rate under its assumptions. It is not a probability statement that the true effect lies in this particular interval. The registry’s sponsor analysis reports a 95% confidence interval from -12.21 to 0.25 for its incidence difference. The two intervals use oppositely directed contrasts, and the sponsor interval is reported on a different displayed scale. The methods and details needed to reconcile their construction are not reported in the registry record.

The primary group counts are 4 of 117 and 11 of 117. With relatively few observed events, each event has a noticeable influence on the group proportions and their comparison. General statistical explanation: sparse event counts often produce substantial uncertainty, even when the point estimates differ. The confidence interval makes that uncertainty visible. Neither the point estimate nor the interval gives information about whether the observed difference would be clinically important; that requires criteria not reported in the registry record.

The reported 95% intervals for the sponsor’s group-level percentages are 1.4 to 9.7 for posaconazole and 8.0 to 21.3 for fluconazole. These are intervals for each group separately, not a direct interval for the between-group contrast. Comparing overlap between separate intervals is not a substitute for a confidence interval on the contrast itself.

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 sample-size planning figures are illustrations based on the observed effect, not the trial’s original design calculation. For the binary outcomes shown, the figures are participants per arm. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. For time-to-event outcomes, the stated convention is total events; that is a different unit from participants per arm.

The 80% power column describes the planned number of participants per arm under the stated assumptions to provide an 80% chance of detecting the specified effect if that effect were the true one and the model assumptions held. The 90% power column describes the corresponding planning number for a 90% chance. These are prospective planning calculations based on assumed effects and analysis conditions. They do not describe the chance that the completed trial detected an effect, and they are not observed power.

Each planning row uses a different fraction of the observed effect: 100%, 75%, or 50%. A smaller effect is harder to distinguish from random variation at the same significance level and target power, so the planning figures increase as the assumed effect becomes smaller. For example, the primary endpoint’s figures are 262 participants per arm for 80% power when planning for 100% of the observed effect, and 819 participants per arm when planning for 50% of the observed effect. These illustrations should not be taken as evidence that the trial was designed around those assumptions. Its original sample-size assumptions and justification 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 = 0.034; treatment proportion p₁ = 0.094; average p̄ = 0.064.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.3464 = 0.6789.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.3438 = 0.2893.
4. n = (0.6789 + 0.2893)² / (0.0598)² = 261.9, rounded up to 262 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 <- 0.0341880341880342                          # control proportion
p1 <- 0.094017094017094                          # 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(811928)
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 = 262 (80% power), 351 (90% power)
 75% of observed effect: n per arm = 416 (80% power), 556 (90% power)
 50% of observed effect: n per arm = 819 (80% power), 1,096 (90% power)
power.prop.test: 261.9 
Simulated power at n = 262 per arm: 0.817 (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 sponsor analysis is labelled as a non-inferiority or equivalence analysis. It reports an incidence difference of -5.88, with a 95% confidence interval from -12.21 to 0.25. No p-value or analysis method is reported alongside that result. The registry record also does not report the non-inferiority margin or equivalence bounds, which are needed to evaluate a formal conclusion under either framework.

The simple recalculation uses the same posted primary group counts but expresses the contrast as fluconazole relative to posaconazole. It gives a risk difference of 0.060, with a 95% confidence interval from -0.003 to 0.122 and an unadjusted p-value of 0.062. Since the sponsor’s contrast runs in the opposite direction, its negative estimate and the recalculated positive estimate should not be read as conflicting directions. The registry does not give enough methodological detail to determine whether their estimates and intervals use otherwise identical methods or scales.

The registry’s sponsor analysis is the trial’s reported analysis and should anchor interpretation. The recalculation is a simple unadjusted comparison of the posted counts, not a replacement for the sponsor’s analysis. The record does not indicate a discrepancy between the posted sponsor result and the underlying counts. Without the margin, analysis method, and full statistical plan, the sponsor’s non-inferiority or equivalence label cannot be translated into a definitive conclusion from the posted interval alone.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and six secondary outcomes. It does not report whether the statistical analysis plan adjusted for multiple comparisons, used a hierarchy of outcomes, or designated which secondary analyses were confirmatory. General statistical explanation: multiple testing concerns arise when several hypotheses are assessed, because the chance of at least one false positive can increase across a family of tests. Adjustment or a prespecified testing order can address this concern, but neither approach should be assumed without documentation. For that reason, unadjusted secondary p-values or intervals, where available, warrant more cautious interpretation than a clearly prespecified primary analysis.

There is no reported description of interim analyses, stopping rules, or adaptations to the study design in the registry record. Those features cannot be inferred from the completed status or the reported results. The record also does not describe whether the primary analysis was stratified, adjusted for covariates, or conducted according to a separate prespecified protocol. The analysis method for the sponsor’s primary comparison is not reported.

The full analysis set included randomized participants who received at least one dose and had at least one post-treatment follow-up datum for the primary efficacy variable. The registry does not provide a detailed accounting of participants excluded from this set, the reasons for exclusion, or missing endpoint data by group. It does not report imputation methods, sensitivity analyses for missing data, or a per-protocol analysis. These omissions make it difficult to assess how incomplete follow-up or analysis-population choices might affect the reported comparison.

General statistical explanation: missing outcomes can affect a group comparison if the likelihood of missingness is related to event status or differs between groups. The direction and size of any such influence cannot be established from the registry information alone. A transparent account of missingness and sensitivity analyses would help readers judge the robustness of the result, but those details are not reported in the registry record.

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: death (1.7%), cerebral haemorrhage (1.6%), bone marrow depression (0.8%), intestinal haemorrhage (0.8%), sepsis (0.8%).

The safety summary uses groups of 124 participants for posaconazole and 121 for fluconazole. Serious adverse events affected 7 participants in the posaconazole group and 10 in the fluconazole group. Other adverse events affected 82 and 81 participants, respectively. These are participant counts, not a measure of event severity beyond the registry’s serious-adverse-event classification, and the posted summary does not give further detail about timing or duration.

The registry lists serious adverse event terms that include Death at 1.7%, Cerebral haemorrhage at 1.6%, Bone marrow depression at 0.8%, Intestinal haemorrhage at 0.8%, Sepsis at 0.8%, and Septic shock at 0.8%. The listed percentages are not presented by treatment group in the record, so they should not be attributed to one group. The safety death counts by group are not reported in the registry record. All-cause mortality is also listed as a separate secondary outcome, with 3 participants in the posaconazole group and 8 in the fluconazole group within 100 days.

These figures describe reported events in this trial; they do not establish a comparative safety profile. The registry does not provide enough detail about event-level definitions, exposure-adjusted rates, or the sponsor’s safety analysis to support broader conclusions.

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

The posted primary counts show fewer proven or probable IFI events in the posaconazole group than in the fluconazole group during the stated treatment-period window. The unadjusted comparison is uncertain: its 95% confidence interval crosses zero, and the unadjusted p-value is 0.062. The sponsor’s own analysis is labelled non-inferiority or equivalence, but the registry does not report the analysis method or decision margin needed to assess that label. The results therefore describe the observed data without establishing superiority, equivalence, or non-inferiority.

General statistical explanation: a trial result is not a direct statement about every patient or every setting. It is an estimate from a particular study population, treatment regimen, outcome definition, and follow-up period. The registry identifies high-risk leukopenic patients and the specified dosing schedules, but fuller eligibility and setting details are not reported in the registry record. The findings should be understood within those boundaries.

The primary endpoint counts participants with an event; it does not capture event timing, duration, severity, or all aspects of treatment experience. The secondary outcomes cover some additional event types and follow-up periods, but their results are incomplete in the detailed registry record. Safety figures also summarize affected participants rather than providing a complete account of each event. The posted results consequently do not answer every question about benefit and harm.

A statistically uncertain estimate is not proof that groups are identical, just as a numerical difference is not proof that one treatment is better. The interval indicates a range of estimates compatible with the recalculation’s assumptions, including values on both sides of zero. The registry does not report a threshold for clinical importance, so the practical meaning of any particular difference cannot be determined from these statistics alone. No treatment decision follows from the results by themselves.

18. Why This Trial Matters Statistically

This trial illustrates why event counts, effect estimates, and uncertainty need to be read together. The raw primary counts are easy to understand, but the comparison is based on relatively few events. The recalculated risk difference gives an absolute comparison, while the confidence interval shows that the estimate remains compatible with a range of effects that includes no difference. Reporting only the event counts or only the point estimate would leave out important information about precision.

It also illustrates that the direction and scale of a contrast matter. The sponsor reports an incidence difference in one direction; the simple recalculation is expressed as fluconazole relative to posaconazole. Recognizing that reversal prevents a misleading reading of the signs. Different scales, such as absolute risk differences and relative measures, answer related but distinct questions and should be interpreted with their definitions in view.

The registry’s non-inferiority or equivalence label highlights a further statistical principle: a conclusion depends on prespecified margins and methods, not only on the sign of an estimate or whether an interval crosses zero. Because the margin and sponsor analysis method are not reported in the registry record, readers cannot verify the formal criteria from the posted figures alone. This is a reporting limitation, not a basis for guessing the intended analysis.

Finally, secondary outcomes and safety summaries add context but do not remove uncertainty in the primary result. Multiplicity, missing outcome information, the full analysis set definition, and open-label ascertainment are all relevant to interpretation. The record demonstrates the value of a complete statistical report that makes the analysis plan and decision criteria visible alongside numerical results.

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 registry record does not report detailed eligibility criteria beyond describing the population as high-risk leukopenic patients. It also does not provide the original sample-size calculation or its assumptions, so the planning illustrations based on observed effects should not be mistaken for the trial’s own design rationale. The statistical method, non-inferiority margin, and formal decision rules for the sponsor’s primary analysis are not reported, limiting independent assessment of the analysis label.

The study was open label. General statistical explanation: when treatment assignment is known, it can potentially influence reporting, clinical management, or assessment of outcomes that require judgment. The registry description says IFI diagnosis criteria may include clinical, microbiological, and symptom-based elements. This creates a relevant potential concern for interpretation, but the record does not establish that assessments were biased or how diagnoses were adjudicated.

The primary full analysis set required at least one dose and at least one post-treatment follow-up datum. The record does not give a detailed participant flow, group-specific missing-data account, imputation approach, or sensitivity analyses. The reported enrollment and primary analysis group sizes are distinct summaries; reasons for the analysis-set membership are not reported in the registry record. Without those details, the impact of exclusions or incomplete follow-up cannot be evaluated.

Detailed numerical results are not available for every listed secondary outcome, and multiplicity handling is not reported. The registry also does not describe interim analyses or provide a complete statistical analysis plan. These reporting gaps constrain interpretation of secondary findings and the robustness of the primary comparison. The safety summary provides affected-participant counts and selected serious-event terms, but not a full event-level account or group-specific breakdown for the listed terms.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Posaconazole vs. Fluconazole for Prevention of Invasive Fungal Infection (P05387 AM1)(COMPLETED) — NCT00811928.
• Registry record last updated 2017-04-07; status last verified 2017-03.
• Results first posted 2011-09-13.
• 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

NCT00811928 is a completed phase 3 randomized, open-label, parallel, multicenter study of posaconazole versus fluconazole for prevention of IFI in high-risk leukopenic patients. The registry reports enrollment of 252. The primary endpoint counted participants with proven or probable IFI during treatment, with assessment up to 12 weeks (84 days) plus 7 days. In the full analysis set, the counts were 4 of 117 for posaconazole and 11 of 117 for fluconazole.

The unadjusted recalculation gives a risk difference of 0.060 for fluconazole relative to posaconazole, with a 95% confidence interval from -0.003 to 0.122 and p = 0.062. The sponsor analysis is labelled non-inferiority or equivalence, but its method and margin are not reported in the registry record. Secondary outcomes and safety summaries provide additional context, with limits arising from incomplete outcome detail and unreported analysis-plan information.