This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Single Dose Population Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients (NCT02968134), a na phase 4 study. The primary outcome is Posaconazole Exposure Described as Area Under the Total Plasma Concentration-time Curve From Time Zero to Infinity After a Single Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02968134 |
| Phase | Phase 4 |
| Condition | Systemic Fungal Infections |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Royal Brisbane and Women's Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Critically ill patients admitted to an intensive care unit with presumed or confirmed systemic fungal infections. The registry record describes an enrollment of 8 patients. It does not report further eligibility details or a breakdown of participant characteristics.
Intervention
A single intravenous dose of posaconazole. The primary outcome description specifies a dose of 300 mg. Serial blood sampling was planned to describe posaconazole concentrations over time after administration.
Comparator
There was no comparator group. The registry identifies a single-group study, with allocation and masking listed as not applicable and none, respectively. Consequently, the design does not support a direct treatment contrast with another drug, dose, or untreated group.
Primary question
What is the plasma exposure to posaconazole after a single intravenous dose in this critically ill population, expressed as the area under the total plasma concentration-time curve from time zero to infinity? This is a pharmacokinetic question about measured drug exposure. The registry record does not report the numerical exposure estimate or its interquartile range.
3. Trial Design
This was a phase 4, completed, single-group pharmacokinetic study sponsored by Royal Brisbane and Women's Hospital. The registry lists an enrollment of 8 and describes patients admitted to intensive care with presumed or confirmed systemic fungal infections. The study was not randomized, had no comparator arm, and was unmasked. These features define a descriptive design rather than a comparative trial.
The registry dates the study start to 2017-01-16 and primary completion to 2017-05-21. Its status is listed as completed. The intervention was posaconazole, administered intravenously as a single dose; the primary outcome description specifies 300 mg. The intended purpose was to characterize how critically ill patients process the drug and to examine whether recommended dosing achieves adequate blood concentrations. The record does not provide a concentration threshold for adequacy, and it does not report a result that answers that question.
Blood concentrations were to be sampled before dosing and at specified times during and after infusion: 15, 45, and 75 minutes during infusion, then 3, 5, 8, 12, 18, 24, 30, 36, and 48 hours. These serial measurements are relevant because pharmacokinetic exposure is described across time rather than by a single concentration alone. The registry does not report how many samples were obtained from each participant, whether any planned samples were missed, or how missing concentration measurements were handled.
The record lists 2 outcome measures but gives a detailed description only for the primary posaconazole exposure endpoint. Details of the other outcome measure are not reported in the registry record. No statistical analysis is listed in the registry. The analysis population, protocol deviations, and any analysis decisions made after data collection 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
| Stage | Posaconazole |
|---|---|
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | Posaconazole |
|---|---|---|
| Participants analysed | 8 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 7 |
| Race and Ethnicity Not Collected | Participants | — |
| BMI | kg/m^2 | 22.6 (20.2 to 29.7) |
| Acute Physiology and Chronic Health Evaluation II Score | units on a scale | 17 (17 to 24) |
| Serum creatinine | umol/L | 106 (78 to 179) |
| Urinary creatinine clearance | mL/min | 74 (53 to 109) |
| Serum albumin | g/L | 20 (18 to 20) |
| ALT | IU/mL | 53 (28 to 60) |
| AST | IU/mL | 47 (38 to 130) |
| ALP | IU/mL | 75 (63 to 108) |
| Total bilirubin | umol/L | 11 (10 to 20) |
| INR | ratio | 1.3 (1.3 to 1.4) |
6. Primary Endpoint
The registry lists the primary outcome as Posaconazole Exposure Described as Area Under the Total Plasma Concentration-time Curve From Time Zero to Infinity After a Single Dose, measured over 48 hours.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | ng*h/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is posaconazole exposure, expressed as the area under the total plasma concentration-time curve from time zero to infinity after a single 300 mg intravenous dose. An area under the curve (AUC) represents overall drug exposure across time: concentrations are considered together with the time over which they are measured. It differs from a concentration measured at one particular sampling time.
Pharmacokinetic studies use exposure measures to describe how a drug enters and moves through the body, and how it is eliminated. In critically ill patients, illness can affect these processes; the study description identifies that concern as its rationale. AUC can therefore be useful when the question is how much drug exposure follows a dose, rather than whether one isolated blood concentration is high or low.
The endpoint specifies exposure through infinity, while the stated sampling schedule extends to 48 hours. AUC to infinity can include an extrapolated portion beyond the observed sampling period, but the registry does not report the calculation method or how much of the endpoint relied on extrapolation. The registry specifies that exposure is to be described by a median and interquartile range. The numerical median and interquartile range are not reported in the registry record, so the observed exposure level and its spread cannot be assessed from that record.
This endpoint is pharmacokinetic, not a direct measure of fungal clearance, clinical recovery, or comparative treatment benefit. The registry does not provide a clinical efficacy result or a threshold against which the reported exposure could be judged.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study asks a focused descriptive question: what plasma exposure follows a single intravenous dose of posaconazole in critically ill patients with presumed or confirmed systemic fungal infections? A single-group design can describe exposure in the enrolled participants, but it cannot establish how that exposure differs from a control group or from another dose. There is no randomized comparison in the registry record.
The record identifies the primary measure as AUC from time zero to infinity and specifies that it is to be summarized by a median and interquartile range. Those statistics would convey the central exposure and its distributional spread. However, neither the numerical estimate nor the interquartile range is reported in the registry record. Without those values, the posted record does not allow a reader to judge the magnitude or precision of the observed exposure. It also does not state a target concentration or exposure level for adequate treatment, so the study rationale about adequate concentrations cannot be converted into a conclusion from the registry information.
The reported endpoint is not an outcome comparison. No control arm, treatment contrast, or inferential test is listed. No analyses are listed in the registry record. This absence does not establish that no analyses were conducted; it means the registry record does not describe them. An effect estimate, confidence interval, p-value, covariate-adjusted result, or model-based exposure estimate is not reported in the registry record.
General statistical interpretation: a confidence interval, when reported, expresses uncertainty around an estimate under the assumptions of the method used. It is not a guarantee that the true value lies in a particular interval. No confidence interval is reported for the primary endpoint in this record. Similarly, a small enrollment can make estimates sensitive to the observations included, but no numerical uncertainty measure is available to quantify that concern.
The registry describes serial sampling through 48 hours and an AUC endpoint extending to infinity. The sampling schedule clarifies the intended observation window, but the record does not explain how concentrations after the final scheduled sample contribute to the endpoint. It also does not report whether all planned samples were collected. Those omissions prevent assessment of the completeness of concentration-time profiles and the role of any extrapolation.
The safety information is descriptive and should be read separately from the pharmacokinetic endpoint. The record reports a serious adverse event and a death in the posaconazole group, but does not establish whether either was caused by posaconazole. Overall, the registry supports describing the study's design, intended exposure measure, and listed safety counts; it does not provide a numerical pharmacokinetic result or a basis for a causal treatment conclusion.
9. Statistical Methods Explained
What does a single-group design tell us?
The study is registered as a single-group study, with allocation listed as not applicable and masking listed as none. In this design, the stated aim is to characterize pharmacokinetics after posaconazole administration in the enrolled population. There is no concurrent comparator group. The results therefore cannot estimate a between-group treatment difference or separate the effect of posaconazole from other influences by comparing trial arms.
General explanation: a descriptive study can estimate quantities such as concentration or exposure in the participants observed. A comparison design is needed to estimate a contrast between interventions, subject to its design and analysis assumptions. Since the registry has no comparator arm, any claim about relative efficacy or relative safety would go beyond this study design.
How are serial concentrations related to AUC?
The registry describes blood sampling before dosing, during infusion, and at later times through 48 hours. Concentration measurements at multiple times form a concentration-time profile. AUC combines information across that profile to represent exposure over time. The primary outcome is specified as AUC from time zero to infinity after a single 300 mg intravenous dose.
General explanation: when concentrations are observed only at scheduled times, an analysis method is needed to estimate the area between measurements. For an endpoint extending beyond the last observation, a method may also estimate the remaining area. The registry record does not report the interpolation, extrapolation, or model-fitting method, nor the fraction of the AUC estimated beyond the last scheduled sample. Those details matter for judging how much the result depends on observed concentrations versus assumptions about the concentration curve.
Why summarize exposure with a median and interquartile range?
The primary outcome description specifies a median and interquartile range. The median describes the central value when observations are ordered; the interquartile range describes spread among observations around that center. These summaries can be useful when a distribution is not well represented by a mean and standard deviation. The registry does not report the actual median or interquartile range, so no specific distributional pattern can be described.
General explanation: pharmacokinetic measurements can vary between people, and a distribution may be skewed. A median is less influenced by very high or low observations than a mean, while the interquartile range gives information about the spread of central observations. Whether this study's data were skewed, or whether other summaries were also calculated, is not reported in the registry record.
What analysis details are available?
No analyses are listed in the registry record. It does not describe an analysis population, statistical model, covariate adjustment, approach to missing measurements, or planned handling of protocol deviations. It also does not report whether interim analyses were conducted. These are not grounds to assume a particular method; they are items whose details are not reported in the registry record.
General explanation: an analysis population states which participants or measurements contribute to a result. Missing-data methods matter when scheduled observations are unavailable, especially for a time-dependent measure that uses a concentration profile. Model choices and assumptions can also affect an estimated exposure. Without these details and the primary numerical result, the registry information is insufficient to reproduce or evaluate the endpoint calculation.
How should planning illustrations be understood?
The registry's planning description specifies a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It says the effect to detect is a stated fraction of an observed effect. Those assumptions describe a planning illustration, not the design used in this single-group study. The trial itself has no two-arm allocation in the registry record.
General explanation: a sample-size calculation asks how many participants a future study might need under stated assumptions about the effect, variability, significance level, and desired power. If the assumed effect is smaller, planning generally requires more information to distinguish it from chance variation. Such calculations are conditional on the assumptions and are not a measure of the probability that this completed study detected an effect. The planning description says the illustrations are not the trial's own design; they should not be read as observed power. Numerical planning outputs and the observed effect used for them are not reported in the registry record.
Over-dispersion is a general concern when observed variation exceeds what a chosen statistical model assumes. In that situation, model-based uncertainty can be understated if the extra variation is ignored. The registry does not report a model for the primary endpoint, a dispersion estimate, or an assessment of over-dispersion, so no conclusion about its presence or handling is possible.
No recalculated comparison is available to interpret from the registry information. The record does not give the primary estimate, its dispersion, or a comparator result. A numerical recalculation would require those inputs and would not substitute for a sponsor's prespecified analysis if the two differed. The registry does not report a sponsor analysis of the primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures, but it provides a detailed description only for the primary posaconazole exposure endpoint. The description of the other outcome measure is not reported in the registry record. No analysis methods are listed, and no multiplicity adjustment or hierarchy among outcomes is reported. It is therefore not possible to determine whether multiple outcomes or analyses were considered together when interpreting statistical evidence.
General explanation: multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. If many tests are conducted, the chance of at least one apparently noteworthy result can increase. A prespecified primary endpoint and an explicit analysis plan can help make the interpretation clearer. The registry identifies a primary endpoint, but does not provide a statistical plan or explain any adjustment for multiple analyses.
Missing-data handling is also not reported in the registry record. The study description specifies a series of planned blood samples, but does not say whether all measurements were obtained, how unavailable samples were handled, or whether any participants were excluded from the primary analysis. These details can affect a concentration-time profile and the resulting AUC.
The registry does not identify an analysis population, such as whether the primary analysis included everyone enrolled or only participants with a complete profile. It does not report the number of participants contributing to the primary endpoint. Interim analyses and rules for stopping or changing analyses are not reported in the registry record. These gaps prevent assessment of how the registered outcomes were translated into analyzed results; they should not be filled by assuming a particular protocol or statistical practice.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Posaconazole | 1 | 8 | 12.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Posaconazole | 1 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Posaconazole | 0 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Posaconazole |
|---|---|---|
| Death | Gastrointestinal disorders | 1 of 8 |
Serious events with the highest arm-level rate: death (12.5%).
The registry reports safety counts for the posaconazole group. Serious adverse events were recorded for 1 participant among 8 at risk. The serious-event term listed is Death, with a reported value of 12.5%. The record also reports 1 death. Other adverse events were recorded for 0 participants among 8 at risk.
These are descriptive counts from a small, single-group study. They do not by themselves show whether an event was caused by posaconazole, whether it arose from the underlying critical illness, or whether another factor contributed. The registry does not provide event narratives, timing, severity details beyond the serious-event classification, or an assessment of relatedness. It also does not report a comparison group against which to interpret the event frequency.
General explanation: an adverse event occurring during a study is not automatically an adverse reaction caused by the study treatment. Attribution requires clinical and temporal information and is not established by a count alone. The safety figures should therefore be read as events recorded in the study, not as proof of causation or as a comparative risk estimate.
12. What the Result Does, and Does Not, Mean
The registry record describes a completed investigation of posaconazole pharmacokinetics in critically ill patients with presumed or confirmed systemic fungal infections. Its central question concerns plasma exposure after a single intravenous dose, with the primary measure defined as AUC from time zero to infinity. It also provides a planned blood-sampling schedule and descriptive safety counts.
The record does not report the numerical primary endpoint result, its interquartile range, or a concentration threshold for adequate exposure. As a result, it cannot establish from the registry information whether the observed exposure was high, low, variable, or sufficient relative to a clinical target. The study purpose mentions assessing recommended doses, but a stated purpose is not itself a reported finding.
The design does not include a comparator group. It therefore does not estimate a difference between posaconazole and another treatment, or between the study dose and another dose. It also does not establish that posaconazole improves clinical outcomes or prevents fungal resistance. Those are distinct questions from describing drug exposure after a dose, and the registry record does not report results that answer them.
The safety counts should likewise not be interpreted as proof of a drug-related harm or as a comparative safety estimate. The record lists a serious adverse event and a death, but does not report causality assessments or a control group. The numerical counts are useful as a description of what was recorded, with the stated limitations.
General explanation: a pharmacokinetic estimate can help characterize drug exposure, but translating exposure into a clinical conclusion requires additional context, such as a prespecified target and relevant clinical outcomes. Neither an unreported estimate nor the study rationale can establish whether a dose is suitable for an individual patient. The registry provides no individual treatment recommendation, and its information should be interpreted as a limited description of a small pharmacokinetic study rather than a comparative clinical-effect result.
13. Why This Trial Matters Statistically
This study illustrates why pharmacokinetic questions can be important in critical care. The registry description notes that serious illness may influence drug concentrations and that blood samples taken over time can be used to study how a drug is processed. For a drug exposure question, the relevant information is not only whether a dose was given, but also the resulting concentration-time profile and the method used to summarize it.
Statistically, the study highlights the distinction between estimating a quantity in a group and comparing interventions. A single-group design can be suited to describing exposure, but it cannot produce a randomized contrast with another treatment. Keeping that distinction clear prevents a pharmacokinetic description from being mistaken for evidence of comparative efficacy or safety.
The endpoint also makes analysis transparency important. AUC from time zero to infinity is based on a concentration-time profile, and the record states that planned sampling continued through 48 hours. Reporting how the profile was analyzed, how any portion beyond sampling was estimated, and how missing samples were handled would help readers evaluate the result. The registry record does not provide those details or the numerical endpoint estimate.
The study is also a reminder that small descriptive datasets can provide a focused account without resolving every clinical question. The registry reports an enrollment of 8 and a single-group design. It does not report a comparator, analysis plan, or numerical primary result. Reading those limits alongside the intended pharmacokinetic question helps distinguish what the study set out to measure from what the registry can support as a conclusion.
14. 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 principal limitation for interpreting the registry record is that it does not report the numerical primary exposure estimate or its interquartile range. Although the endpoint and summary form are specified, the reported material does not allow readers to assess the observed exposure or its variability. The second listed outcome measure is not described in detail in the registry record.
The study is a single-group investigation with an enrollment of 8. It has no comparator arm, so it cannot provide a direct treatment comparison. Its results, even if reported, would describe the enrolled participants and would not by themselves demonstrate a causal effect on clinical outcomes. The registry does not report participant characteristics beyond the description of critical illness and presumed or confirmed systemic fungal infection, limiting assessment of how the enrolled group relates to other populations.
The planned sample collection extends to 48 hours, while the endpoint is AUC from time zero to infinity. The registry does not report the calculation method, the contribution from beyond the sampling period, whether all planned samples were collected, or how missing measurements were handled. Those omissions limit evaluation of the endpoint's construction.
The registry does not list statistical analyses or describe the analysis population, model, covariate handling, multiplicity approach, or interim analyses. It also does not report a prespecified target exposure that could define adequacy. The safety listing lacks event narratives, relatedness assessments, and a comparison group. These limitations concern what can be concluded from the registry record; they do not establish that any particular method or procedure was or was not used outside the recorded information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Single Dose Population Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients — NCT02968134.
- Registry record last updated 2018-09-21; status last verified 2018-08.
- Results first posted 2018-07-09.
- 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.
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18. Record Summary
NCT02968134 is a completed phase 4, single-group study titled “Single Dose Population Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients,” sponsored by Royal Brisbane and Women's Hospital. The registry lists an enrollment of 8, a start date of 2017-01-16, and primary completion on 2017-05-21. The study was unmasked and had no comparator group.
The primary endpoint is posaconazole AUC from time zero to infinity after a single intravenous dose of 300 mg, summarized as a median and interquartile range. Blood sampling was planned from before dosing through 48 hours. The numerical primary result, its interquartile range, and details of the statistical analysis are not reported in the registry record.
The registry lists 2 outcome measures, but the second is not described in detail. Safety information includes 1 serious adverse event among 8 at risk, Death listed as a serious-event term at 12.5%, 1 death, and 0 other adverse events among 8 at risk. No causal attribution is reported.