Fungal Prophylaxis With Isavuconazole for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HCT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fungal Prophylaxis With Isavuconazole for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HCT) (NCT03149055), a na phase 2 study. The primary outcome is Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT).

2. Clinical Question

3. Trial Design

This was a phase 2, single-center, open-label trial of isavuconazole prophylaxis in patients undergoing allogeneic HCT. The registry identifies Memorial Sloan Kettering Cancer Center as the sponsor and lists the study as completed. The recorded start date is 2017-05-04, and the primary completion date is 2019-08-20. Enrollment was 99.

The study used a single group receiving isavuconazole, rather than a randomized allocation to separate treatment groups. Allocation is listed as not applicable, and masking as none. Thus, the design can describe outcomes among participants enrolled in the study, but it does not furnish a concurrent control group for estimating a between-group treatment contrast. The registry record does not report a comparator-based statistical analysis.

The intervention could be given intravenously or orally. The listed regimen was isavuconazonium sulfate 372 mg every 8 hours for 6 loading doses, followed by 372 mg daily as maintenance. The minimum duration of prophylaxis was through D +60. Discontinuation beyond day +60 was left to the treating physician’s discretion.

The primary outcome was clinical failure by week +14 after HCT, with a stated timeframe of 14 weeks post HCT. The registry record lists 2 outcome measures and 0 analyses. It does not report the primary-outcome result, a statistical analysis plan, a sample-size justification, or details of interim analyses. Those omissions limit interpretation of how the study’s observations were analyzed and how its design was intended to address uncertainty.

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:

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 Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT), measured over 14 weeks post HCT.

The primary endpoint is the count of participants with clinical failure of isavuconazole prophylaxis by week +14 after HCT. It is a participant-count outcome, not a time-to-event measure in the information recorded for the primary endpoint. The timeframe is 14 weeks post HCT.

Clinical failure includes any of four stated events: systemic antifungal therapy for more than 14 consecutive days for suspected fungal infection up to week 14; breakthrough proven or probable fungal infection during the prophylaxis phase; toxicity leading to permanent discontinuation of prophylaxis; or an adverse event requiring discontinuation. The registry defines the prophylaxis phase as the period from the first isavuconazole dose through 7 days after discontinuation.

In general, a composite endpoint combines multiple types of event into one outcome. This can capture several ways a prophylaxis course may fail, but the combined count does not by itself show which component occurred or how frequently each component occurred. The registry record does not report component-specific counts or the overall number meeting the primary endpoint. Therefore, the endpoint definition is available, but its observed result and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The reported primary outcome is a count of participants who met a binary definition of clinical failure by the stated follow-up point. For a binary outcome, each participant is classified as meeting or not meeting the endpoint according to the endpoint rules. A count describes how many participants had the event; a proportion would also require a defined denominator. The registry record gives the endpoint unit as participants, but does not report the primary-outcome count or the denominator used for its analysis.

What a confidence interval would describe

General statistical explanation: a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. For a single-group event proportion, an interval would describe the precision of the estimated event frequency in the population represented by the analysis. A narrow interval generally indicates greater precision than a wide interval, while neither interval width nor the estimate alone establishes a causal treatment effect. The registry record does not report a primary-outcome estimate or confidence interval, so the precision of the clinical-failure result cannot be evaluated.

Why the study design matters

General statistical explanation: random allocation to a concurrent comparator can help balance, on average, factors that might otherwise differ between groups. A single-group study has no such randomized contrast. Its outcomes can be reported descriptively, but a comparison with an external expectation or historical experience would require additional information and assumptions. No such comparator or comparative analysis is reported in the registry record.

The record labels the study open-label and lists masking as none. General explanation: when treatment assignment is known, decisions or assessments that involve judgment can potentially be influenced by that knowledge. The clinical-failure definition contains clinical events and treatment-discontinuation criteria, but the registry record does not describe blinded endpoint adjudication or other procedures for reducing assessment bias. It would be unwarranted to assume either that these procedures were used or that they were absent beyond what the registry records.

How to read the planning assumptions

The record describes a sample-size planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These statements describe the assumptions attached to a planning illustration; they are not a report of the trial’s own design, which is recorded as single-group. The numerical illustration results and the observed effect used as its reference are not reported in the registry record.

General statistical explanation: a planning calculation estimates how much information a hypothetical design might require under chosen assumptions about the effect, variability, significance threshold, and allocation. Changing those assumptions can change the planning result. A planning calculation is not an observed result, and it is not observed power. In particular, a calculation based on an observed effect should not be treated as a prespecified justification for the study or as evidence that the study had a given probability of detecting an effect.

What is not available for reanalysis

The registry record lists 0 analyses and does not report a primary-outcome count, effect estimate, confidence interval, or test result. It also does not provide participant-level data or enough primary-outcome summary information to recalculate an estimate. No recalculated result can therefore be interpreted. The record does not state whether any analyses were adjusted, what model or test was used, or how covariates were selected. Those details are not reported in the registry record.

General statistical explanation: model choice should follow the outcome type, design, and analysis question. For a count of participants meeting a binary endpoint, methods commonly focus on an event proportion or a contrast between proportions when a valid comparison group exists. In a single-group study, there is no internal between-arm contrast to estimate. Selecting a different model cannot create a concurrent comparator or recover results that have not been reported.

The endpoint is composite, so an overall result would need interpretation alongside its components. General explanation: a combined endpoint can summarize whether any qualifying event occurred, but components may differ in clinical meaning and frequency. Component-level results help readers understand what drives a composite count. The registry record does not report component-specific counts, so it is not possible to determine which criteria contributed to clinical failures.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures and identifies clinical failure by week +14 as the primary outcome. It lists 0 analyses. No multiplicity procedure, hierarchy of statistical tests, or adjustment for testing multiple outcomes is reported in the registry record. Therefore, the effect of any multiplicity strategy on interpretation cannot be assessed.

General statistical explanation: when multiple outcomes or hypotheses are tested, the chance of at least one apparently notable result can increase if the analyses are treated as independent opportunities without an appropriate plan. A prespecified hierarchy or adjustment can address some multiplicity concerns. The record does not state whether such methods were planned or used, so none should be inferred.

The registry record does not report the number of participants with missing primary-outcome data, reasons for missingness, or methods for handling missing observations. It also does not describe an analysis population, such as whether results were based on all enrolled participants or a narrower group. The enrollment of 99 and the safety denominator of 95 do not establish the primary-outcome denominator. Their relationship is not reported in the registry record.

General statistical explanation: missing outcome data can affect both the number of participants contributing to an estimate and the interpretation of that estimate, particularly if missingness is related to outcome status. Analysis-population definitions clarify who contributes to each result. Without the registry’s missing-data and population details, neither the possible impact of missing observations nor the population represented by a primary-outcome estimate can be evaluated.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 95 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 95 at risk and 7 affected. It also records 6 deaths. These are the safety counts entered in the registry; they should be read as separate reported categories rather than combined into a new total.

The record does not list top serious adverse-event terms. It also does not provide details in this information about event timing, duration, severity grades, relatedness to isavuconazole, or whether events led to discontinuation. The 6 deaths are reported as a count, without further characterization in the registry information. The relationship between the safety denominator of 95 and the enrollment of 99 is not reported in the registry record.

These safety counts are descriptive. They do not, by themselves, establish a comparison with another treatment or explain the cause of an event. The serious-adverse-event count is also distinct from the primary clinical-failure endpoint: that endpoint includes specific infection, antifungal-treatment, toxicity, and discontinuation criteria. No primary-endpoint count is reported in the registry record.

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

The record identifies a completed, phase 2, open-label, single-group study of isavuconazole prophylaxis in people undergoing allogeneic HCT. It specifies the regimen and a primary clinical-failure endpoint assessed by week +14. It also records safety counts. These details describe the study question and some recorded observations, but the primary outcome result is not reported.

Because the registry record does not report the number of participants meeting clinical failure, it does not establish the observed frequency of that endpoint or its precision. The safety counts provide limited descriptive information, but they do not indicate how outcomes compare with an alternative strategy. No randomized comparator group is listed, and no comparative analysis is reported.

General statistical explanation: an observed outcome in a single group can reflect the intervention, participant characteristics, clinical care, follow-up, and other influences. Without a suitable comparison, those influences cannot be separated by a treatment contrast within the study. This limitation does not make descriptive results meaningless; it defines the narrower question they can answer.

The registry record also does not report the primary-outcome analysis population, missing-data handling, or component-level results for the composite endpoint. These omissions prevent a fuller assessment of who contributed to the endpoint analysis and what types of events made up any clinical failures. The planning illustration cannot fill those gaps: its assumptions are not the observed outcome, and its numerical results are not reported.

Accordingly, the record supports a description of the study design, endpoint definition, intervention, and listed safety counts. It does not support a conclusion about the comparative effect of isavuconazole, the primary endpoint’s observed rate, or the statistical precision of that rate. Those conclusions require results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why design and result reporting need to be considered together. A clear endpoint definition tells readers what was intended to count as clinical failure, while the single-group design limits what can be learned about comparative effects. The registry record describes both features, so readers can distinguish an endpoint assessment from a randomized treatment comparison.

The endpoint is composite: it combines prolonged systemic antifungal treatment for suspected infection, breakthrough infection, and discontinuation related to toxicity or an adverse event. General statistical explanation: composite outcomes can capture multiple forms of failure, but a single combined count can conceal differences among components. Component-specific counts are important for understanding what the overall endpoint represents. Those counts are not reported in the registry record.

The safety information also demonstrates the importance of denominators and context. The record lists 95 at risk in two adverse-event categories, alongside enrollment of 99, but does not explain the denominator relationship. It reports 6 deaths without further detail in the recorded information. Readers should keep these counts descriptive rather than infer causes or comparisons that the record does not supply.

Finally, the planning illustration is not the same as a trial’s prespecified design or an observed treatment effect. The record states planning assumptions, but does not report the numerical planning results or primary-outcome analysis. Distinguishing planning from analysis prevents a hypothetical sample-size calculation from being mistaken for evidence about study precision or efficacy. In this case, the absence of a reported primary result is central to statistical interpretation.

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 primary limitation for interpreting the clinical question is that the registry record does not report the primary-outcome result. Although the endpoint and timeframe are defined, there is no event count, estimate, confidence interval, or test result to describe its observed frequency or precision. The record also does not provide component-specific clinical-failure results.

The study is recorded as single-group, open-label, and without masking. No concurrent control group is listed, so the design does not support a randomized comparison. The registry record does not report whether any external comparator was used in an analysis. It also does not describe endpoint adjudication procedures, making it unclear from this record how assessments were standardized.

Enrollment is recorded as 99, while safety categories list 95 participants at risk. The record does not explain the difference or state the primary-outcome analysis denominator. Missing-outcome counts, reasons for missingness, missing-data methods, and analysis-population definitions are not reported in the registry record.

The safety information is limited to counts: 0 affected among 95 at risk for serious adverse events, 7 affected among 95 at risk for other adverse events, and 6 deaths. The record does not provide event-level details or top serious-event terms. It therefore offers limited context for interpreting the safety counts.

Finally, the record lists 0 analyses and does not report a statistical analysis plan, multiplicity handling, a sample-size justification, or interim-analysis details. The planning illustration’s assumptions are described, but its numerical results are not. These reporting gaps constrain assessment of both the analysis and the strength of conclusions that can be drawn from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Fungal Prophylaxis With Isavuconazole for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HCT) — NCT03149055.
• Registry record last updated 2025-05-16; status last verified 2021-11.
• Results first posted 2020-08-20.
• 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.

18. Record Summary

NCT03149055 is a completed phase 2, single-center, open-label, single-group study sponsored by Memorial Sloan Kettering Cancer Center. It enrolled 99 participants undergoing allogeneic HCT and examined intravenous or oral isavuconazole prophylaxis. The listed regimen was a 372 mg loading dose every 8 hours for 6 doses, followed by 372 mg daily. The minimum duration was through D +60, with later discontinuation at the treating physician’s discretion.

The primary outcome was clinical failure by week +14 after HCT, defined by antifungal-treatment, breakthrough-infection, and discontinuation criteria. The registry record does not report the primary-outcome result. Safety counts include 0 serious adverse events among 95 at risk, 7 other adverse events among 95 at risk, and 6 deaths. The record lists 0 analyses and does not report a concurrent comparator, analysis population, or missing-data methods.