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 Topical Phenylephrine Solution in Preventing Oral Mucosa in Bone Marrow Transplant Patients Receiving Cyclophosphamide and Total Body Radiation Therapy (NCT02434146), a na phase 1, phase 2 study. The primary outcome is Area Under the Curve (AUC) for the Oral Mucositis Severity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02434146 |
| Phase | Phase 1, Phase 2 |
| Condition | Neoplasm, Oral Mucosa, Transplant-Related Disorder |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Wisconsin, Madison |
| Results posted | Yes |
2. Clinical Question
Population
Patients undergoing bone marrow transplantation after a regimen of cyclophosphamide and total body irradiation were the intended population. The record lists neoplasm, oral mucosa, and transplant-related disorder among the conditions. The study closed prematurely because of decreased numbers of eligible subjects, and the full target accrual number was not achieved.
Intervention
The intervention was topical phenylephrine solution applied as a spray to the oral mucosa. The arm description states that application was scheduled around cyclophosphamide infusions, including before and after the beginning of an infusion. The description is incomplete in the registry record, so the complete dosing schedule cannot be reconstructed from it.
Comparator
This was a single-group study with no randomized comparison. The record describes an intended analysis involving historical controls, but does not provide their results or enough information to assess how those controls were selected or compared. The supportive-care arm label does not establish a separate control group.
Primary question
The planned primary question was whether oral mucositis severity, summarized over time by an area under the curve (AUC), could be evaluated in patients receiving topical phenylephrine during their transplant-conditioning regimen. The primary outcome was intended to cover up to 3 months. The record states that the AUC could not be estimated or analyzed because the study closed prematurely and did not reach its full target accrual.
3. Trial Design
NCT02434146 is recorded as a phase I/II study sponsored by the University of Wisconsin, Madison. Its official title describes a safety and efficacy study of topical phenylephrine applied to oral mucosa in bone marrow transplant patients receiving Cytoxan plus total body irradiation. The registry lists a single-group model, no masking, and allocation as not applicable. Thus, the design is not a randomized comparison between phenylephrine and a concurrently assigned control group.
The study began on 2015-05-14, had a primary completion date of 2016-04-27, and is listed as terminated. Enrollment is recorded as 3. The registry explains that the study closed prematurely because of decreased numbers of eligible subjects; the full target accrual number was not achieved. The planned primary outcome could consequently not be estimated or analyzed.
The intervention was topical phenylephrine solution applied to oral mucosa. The arm description places applications around cyclophosphamide infusions and refers to an application before each radiation treatment, but the recorded text is truncated. Details beyond the intact description are not reported in the registry record. The outcome description says that the planned AUC analysis would include both an extended cohort and historical controls. The record does not establish that historical controls were a randomized or concurrent comparison group, nor does it provide their results.
There are 9 listed outcome measures and 0 listed analyses. The record does not report a completed primary-outcome estimate, a treatment-effect estimate, or an inferential comparison. The distinction matters: the presence of a planned endpoint and an analysis description does not mean that the endpoint was successfully measured or that the planned analysis was carried out.
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 | Supportive Care (Topical Phenylephrine Solution) |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: This study was closed prematurely due to decreased numbers of eligible subjects. The full target accrual number was not achieved, and AUC could not be estimated or analyzed.
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 | Supportive Care (Topical Phenylephrine Solution) |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Curve (AUC) for the Oral Mucositis Severity, measured over Up to 3 months.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the area under the curve (AUC) for oral mucositis severity, with a timeframe of up to 3 months. An AUC combines measurements of severity across a period of observation into a single summary. In general, it can reflect both the level of severity and how that severity changes over time, rather than relying on a single measurement. Its interpretation depends on the measurements and timing used to construct it.
The registry describes estimating this AUC with the trapezoid method and summarizing it using the mean, standard deviation, median, and range. In general, the trapezoid method approximates the area under a curve by connecting observed values across time intervals and summing the resulting areas. It requires usable measurements over time; missing or sparse observations can affect the approximation and its interpretation.
A longitudinal summary can be useful when the clinical question concerns the overall course of mucositis rather than only its severity at one time. However, the AUC is not a direct measure of a treatment effect by itself. A comparison or other interpretive context is needed to assess what a given value means. The registry explicitly states that the AUC could not be estimated or analyzed because the study closed prematurely and did not reach its full target accrual. No primary AUC estimate or associated summary statistics are reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the planned primary endpoint was not estimated or analyzed. The registry states that the study closed prematurely because of decreased numbers of eligible subjects and did not achieve its full target accrual. Enrollment is recorded as 3. This leaves no reported primary AUC result with which to describe the observed course of oral mucositis severity in the study population.
The study was single-group, with allocation listed as not applicable and masking listed as none. It therefore does not provide a randomized, like-for-like comparison of topical phenylephrine with a concurrent control. Although the outcome description mentions an extended cohort and historical controls, no historical-control results or comparison estimates are reported. Historical comparisons, in general, can be affected by differences in patient selection, clinical practice, measurement, and follow-up; the registry record does not provide enough detail to assess those issues for this study.
The posted results include adverse-event counts, but these are not substitutes for the missing primary endpoint. Serious adverse events were recorded for 0 of 3 at risk, while other adverse events were recorded for 3 of 3 at risk. These counts describe the registered safety categories and do not establish an effect on mucositis severity. The record lists no serious adverse-event terms. It also records 0 deaths. The limited enrollment and absence of a primary outcome estimate constrain how much can be concluded from the safety counts, especially about events that might not appear in a small study.
The registry lists 9 outcome measures but 0 analyses. It does not report a treatment-effect estimate, confidence interval, p-value, or completed analysis of the primary outcome. Without an estimated AUC or a valid comparison, there is no statistical estimate of the magnitude or precision of any effect on mucositis severity in this record. These missing results should not be interpreted as evidence that the intervention had no effect; the endpoint was not analyzed.
In statistical terms, the evidence recorded is chiefly about study conduct and the availability of results: a small enrollment, early termination, and failure to estimate the planned primary endpoint. It does not support a precise estimate of efficacy, and it does not permit a randomized treatment comparison. The registry record does not report whether any interim analysis was planned or performed, or whether a formal sample-size justification was used. Those omissions limit evaluation of the original statistical plan, but do not change the key interpretive point that the primary outcome is unavailable.
9. Statistical Methods Explained
The registry describes a planned analysis of oral mucositis severity using an area under the curve (AUC). AUC is a way to reduce a sequence of measurements over time to a single summary. In general, a larger AUC can reflect greater severity, longer duration, or both, depending on how severity is measured and how the observation period is defined. It cannot reveal every feature of the course on its own: different patterns over time can produce similar summaries.
How would the trapezoid method work?
The outcome description specifies the trapezoid method. In general, this method approximates a curve by joining observed measurements at adjacent time points with straight lines. The area between each pair of observations is approximated as a trapezoid, and those areas are combined into an AUC. The calculation depends on having severity measurements and their timing. The registry record does not report the actual measurement sequence, the number or timing of observations, or an estimated AUC. It states directly that the AUC could not be estimated or analyzed.
What do the planned summaries describe?
The registry says the AUC would be summarized by the mean, standard deviation, median, and range. In general, the mean describes the average, while the median describes the midpoint of the observed distribution. The standard deviation describes spread around the mean, and the range gives the lowest and highest observed values. These summaries answer different descriptive questions; none alone establishes a treatment effect. With enrollment recorded as 3 and no primary AUC estimate, these planned summaries are not available for interpreting mucositis severity.
What can a single-group design establish?
A single-group design records outcomes among participants receiving the intervention but lacks a randomized concurrent group for direct comparison. General changes over time, background risk, other aspects of care, and participant characteristics can all contribute to observed outcomes. A comparison with historical controls may offer context, but it is not equivalent to random assignment. The registry mentions historical controls in the planned AUC description without reporting their results or the details needed to assess comparability. The record also specifies no masking.
How should uncertainty be assessed?
In general, a confidence interval expresses the range of estimates compatible with the data under a specified statistical model and procedure. Its width conveys precision: wider intervals indicate less precise estimates. No confidence interval for the primary AUC or a treatment contrast is reported in the registry record, so precision for the primary question cannot be evaluated. A missing estimate is not the same as an estimate with a wide interval, and it should not be treated as a precise null finding.
General statistical methods also depend on the data structure and distribution. Over-dispersion, for example, occurs when observed variability is greater than a model assumes; accounting for it can prevent uncertainty from being understated. The registry does not report a completed primary-outcome model, its assumptions, or any assessment of over-dispersion. No particular model or adjustment should therefore be inferred.
What do planning calculations represent?
Any sample-size illustrations associated with the record are planning calculations, not observed results or evidence that the study had a particular probability of detecting an effect. The record describes those illustrations as based on an observed effect and states assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are generic planning assumptions, not the trial's own design; the trial itself is listed as single-group. Because the primary AUC could not be estimated or analyzed, the record does not provide a usable primary-endpoint effect estimate to interpret as a completed trial finding. A sample-size illustration cannot replace the missing endpoint analysis.
The registry records 0 analyses. It does not report the analysis populations, handling of missing observations, model specification, or a completed comparison with historical controls. Without those details and without the primary endpoint estimate, the planned statistical methods describe intentions rather than an analysis that can be assessed from results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 9 outcome measures and 0 analyses. It does not report whether the outcomes were organized into primary and secondary families beyond identifying the primary AUC endpoint, or whether any multiplicity procedure was planned. In general, evaluating multiple outcomes can increase the chance of finding an apparently notable result by chance when many statistical tests are performed. The record does not report a multiplicity adjustment, and no inferential analyses are listed to evaluate.
The primary outcome description states that the AUC could not be estimated or analyzed because the study closed prematurely and the full target accrual number was not achieved. The registry does not report the number or pattern of missing mucositis measurements, reasons for missing observations beyond early closure and reduced eligible-subject numbers, or a method for handling missing data. It is therefore not possible to assess whether missingness might have affected an AUC calculation or any other outcome.
Analysis populations are not reported in the registry record. The description refers to an extended cohort and historical controls, but does not provide population definitions, inclusion rules, or results for either group. The record also does not report an interim analysis or a statistical plan for selecting observations for analysis. These omissions leave uncertainty about which participants and measurements were intended for each analysis. They do not support an assumption that a particular missing-data method, multiplicity correction, or analysis population was used.
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 |
|---|---|---|---|
| Supportive Care (Topical Phenylephrine Solution) | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Supportive Care (Topical Phenylephrine Solution) | 0 of 3 |
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 |
|---|---|
| Supportive Care (Topical Phenylephrine Solution) | 3 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Supportive Care (Topical Phenylephrine Solution) |
|---|---|---|
| Grade 2/3 mucositis | Gastrointestinal disorders | 3 of 3 |
The safety results distinguish serious adverse events from other adverse events. In the supportive-care group receiving topical phenylephrine solution, 0 of 3 at risk had a reported serious adverse event, and 3 of 3 at risk had a reported other adverse event. The record lists 0 deaths. No serious adverse-event terms are listed.
These are counts for the registry's recorded categories, not estimates of comparative risk: the study has a single group and no randomized control arm. The counts also do not establish whether an event was caused by phenylephrine or by the underlying treatment context. The registry record does not provide event descriptions for the other adverse events, their timing, severity, duration, or relationship to study treatment. It is therefore not possible to interpret what those events were or how they affected participants from these figures alone.
In general, absence of a recorded serious event in a small study does not rule out uncommon harms or precisely characterize safety. The available counts should be read as a limited description of events recorded in this study, not as proof of safety or as a comparison with another regimen. They also do not address the unreported primary mucositis AUC.
12. What the Result Does, and Does Not, Mean
The record documents a phase I/II, single-group study of topical phenylephrine solution in bone marrow transplant patients receiving cyclophosphamide and total body irradiation. It records enrollment of 3 and a terminated status. The stated reason for premature closure was decreased numbers of eligible subjects, and the full target accrual number was not achieved.
The planned primary outcome was an AUC for oral mucositis severity over up to 3 months. The registry says that this AUC could not be estimated or analyzed. As a result, the record does not establish the observed severity course through a primary endpoint estimate, and it supplies no estimate of the magnitude or precision of an effect on mucositis. The absence of an estimate is not evidence that there was no effect.
The study design also limits causal interpretation. A single-group study does not provide a randomized comparison, and historical controls mentioned in the endpoint description are not reported as results. No treatment contrast, confidence interval, or p-value is available. The safety counts describe reported adverse-event categories in the study group, but do not show whether an event was caused by the intervention or how those counts compare with outcomes under another treatment.
Accordingly, the record supports a description of the study's design, early closure, and limited safety counts. It does not support a quantitative conclusion about efficacy or a comparative conclusion about safety. The registry does not report a completed analysis of the primary outcome, the analysis populations, or the handling of missing data. Those limits should remain central when interpreting the study rather than treating the planned analysis as if it had produced results.
13. Why This Trial Matters Statistically
This study illustrates an important distinction between a registered clinical question and an answer supported by analyzed results. The primary endpoint was specified as an AUC for oral mucositis severity, with a defined general approach for estimation and descriptive summaries. Yet the record states that the AUC could not be estimated or analyzed after premature closure. The planned outcome therefore cannot be treated as an observed finding.
The registry also illustrates why study design matters to interpretation. A single-group study can describe outcomes among participants receiving an intervention, but it does not create the balance that random allocation is intended to achieve between treatment groups. Historical controls may supply context, but the registry does not report their results or enough details to evaluate comparability. Without a completed endpoint analysis and an appropriate comparison, a treatment effect cannot be quantified from this record.
Finally, the study highlights the difference between safety counts and a broad safety conclusion. The posted counts include no recorded serious adverse events, other adverse events among all participants at risk, and no deaths. Those observations are informative as recorded, but the limited enrollment and absent event details leave substantial uncertainty about the safety profile. The statistical lesson is not that the intervention has a particular effect; it is that incomplete accrual and unavailable primary results sharply limit what can be learned from the study.
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 most direct limitation is that the planned primary endpoint was not estimated or analyzed. The registry attributes this to premature closure because of decreased numbers of eligible subjects and failure to achieve the full target accrual. Enrollment is recorded as 3, which offers little basis for precise characterization of outcomes. No primary AUC summary statistics or effect estimate are reported.
The single-group design does not include a randomized comparator. Although historical controls are mentioned in the endpoint description, their data and the methods for selecting or matching them are not reported. The lack of masking is also recorded. The registry does not provide enough information to determine how outcome assessment was conducted or whether knowledge of treatment could have influenced measurement.
The intervention description is truncated, and the complete application schedule is not reported in the registry record. Measurement details for the primary endpoint—including the observed measurement times and the mucositis severity data—are also unavailable. The record does not report missing-data methods, analysis populations, statistical model details, a multiplicity plan, or whether interim analyses occurred. These gaps prevent assessment of the planned analysis beyond its stated use of the trapezoid method and descriptive summaries.
Safety interpretation is limited by the small enrollment and lack of detailed descriptions for other adverse events. The record does not report the events' timing, severity, or relationship to treatment. Taken together, these limitations mean that the posted record is informative about the study's intended question and early termination, but does not provide a completed efficacy analysis or a comprehensive comparative safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Topical Phenylephrine Solution in Preventing Oral Mucosa in Bone Marrow Transplant Patients Receiving Cyclophosphamide and Total Body Radiation Therapy — NCT02434146.
- Registry record last updated 2019-12-09; status last verified 2017-09.
- Results first posted 2017-04-27.
- 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
NCT02434146 was a phase I/II, single-group study of topical phenylephrine solution applied to oral mucosa in bone marrow transplant patients receiving cyclophosphamide and total body irradiation. The study is listed as terminated, with enrollment of 3. The registry states that it closed prematurely because of decreased numbers of eligible subjects and did not reach its full target accrual.
The primary endpoint was oral mucositis severity AUC over up to 3 months. Although the planned method was the trapezoid method, the registry states that the AUC could not be estimated or analyzed. There are 9 listed outcome measures and 0 listed analyses. No primary effect estimate or randomized comparison is reported.
The safety record lists 0 serious adverse events among 3 at risk, other adverse events among 3 at risk, and 0 deaths. These counts are descriptive and do not establish comparative safety or causation. The record does not report detailed event descriptions or the completed analysis methods.