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 Investigating the Use of Prolia (Denosumab) in the Treatment of Acute Charcot Neuroarthropathy (NCT03174366), a na phase 3 study. The primary outcome is Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03174366 |
| Phase | Phase 3 |
| Condition | Charcot Joint of Foot |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 7 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Western University of Health Sciences |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with acute Charcot neuroarthropathy, a condition affecting the foot, and the registry lists Charcot Joint of Foot. The registry summary describes Charcot neuroarthropathy as primarily affecting poorly controlled diabetic patients with peripheral neuropathy. Enrollment was 7. The registry does not report further details about participants’ characteristics, eligibility criteria, disease severity, or how many participants had each characteristic. Those omissions limit how specifically the population represented by this study can be described.
Intervention
The intervention was denosumab, identified in the registry as a drug. The study description says participants in the intervention group received medication, denosumab, and frames the study as a pilot investigation of its potential for acute-stage Charcot neuroarthropathy. The registry record does not report a dosing schedule or other administration details. This study therefore provides a description of the intervention under investigation, but the record does not give enough information to characterize its administration beyond the drug name.
Comparator
No comparator group is listed. The design is single-group, allocation is recorded as not applicable, and masking is none. Consequently, the posted safety counts describe the intervention group without a like-for-like control group in this trial. There is no within-trial comparison that could distinguish the observed event experience from what might have occurred under another treatment or without denosumab. This is a design feature, not evidence that a comparison found no difference.
Primary question
The primary endpoint concerns the incidence of treatment-emergent adverse events for safety and tolerability, measured as participants and assessed over 1 year. The registry also reports serious and other adverse-event counts. These counts describe observed safety events in the treated group; they do not establish whether events were caused by treatment. The record does not report an efficacy primary endpoint. A secondary outcome concerns change in skin temperature difference between the affected and non-affected limb at 6 months, but a result for that outcome is not reported in the registry record.
3. Trial Design
NCT03174366 is a completed phase 3 study sponsored by Western University of Health Sciences. Its title is “Investigating the Use of Prolia (Denosumab) in the Treatment of Acute Charcot Neuroarthropathy.” The registry lists a single-group model, allocation as not applicable, and no masking. It describes one intervention group receiving denosumab, with enrollment of 7. The study began on 2017-05-16, and primary completion was recorded as 2018-06-18. The record status is completed.
In a single-group design, outcomes are observed among participants receiving the intervention, without a concurrent comparison group within the trial. This can describe what happened to participants in the group, but it does not by itself estimate a treatment contrast. The absence of a randomized comparison is particularly important when interpreting event counts: events may reflect the condition, other circumstances, treatment, or several influences, and the design does not separate those possibilities.
The primary outcome is the incidence of treatment-emergent adverse events, measured as participants over 1 year. The registry also lists a secondary outcome: change in the skin temperature difference, in degrees Celsius, between the affected and non-affected limb at 6 months. The record lists 2 outcome measures and 0 analysis records. It does not report a result for the skin-temperature outcome or an inferential analysis of the primary endpoint.
The study summary calls the investigation a pilot study of denosumab’s potential in acute-stage Charcot neuroarthropathy. That description does not supply a detailed protocol or a justification for the enrollment size. A sample-size justification is not reported in the registry record. Nor does the record specify a control condition, masking procedure, or allocation process beyond the listed design classifications. The completed status indicates the study is recorded as completed; it does not, on its own, supply missing outcome analyses or establish what conclusions can be drawn.
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 | Intervention Group, Receiving Medication |
|---|---|
| STARTED | 7 |
| COMPLETED | 7 |
| 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 | Intervention Group, Receiving Medication |
|---|---|---|
| Participants analysed | 7 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 |
| Age, Categorical: >=65 years | Participants | 1 |
| Age, Continuous | years | 50 (SD 10.14) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 3 |
| Race/Ethnicity, Customized: Race/Ethnicity – Hispanic | Participants | 4 |
| Race/Ethnicity, Customized: Race/Ethnicity – African-American | Participants | 1 |
| Race/Ethnicity, Customized: Race/Ethnicity – Mixed Hispanic/Native American | Participants | 1 |
| Race/Ethnicity, Customized: Race/Ethnicity – Pacific Islander | Participants | 1 |
| Region of Enrollment: United States | participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], measured over 1 year.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the incidence of treatment-emergent adverse events, described as a safety and tolerability outcome. It is measured as participants, with a timeframe of 1 year. In general, an incidence endpoint asks whether participants experienced an event during a defined observation period. Reporting participants rather than only event episodes can make clear how many people were affected, although interpretation also depends on the event definition, ascertainment procedures, and completeness of follow-up.
The registry record reports serious and other adverse-event counts separately, as well as deaths. It records 0 participants with serious adverse events among 7 at risk, and 2 participants with other adverse events among 7 at risk; deaths are recorded as 0. The record does not name the other events or provide enough detail to determine how the categories were defined or whether any individual experienced events in more than one category. These category counts should therefore not be added together or treated as a complete description of all event episodes.
Safety and tolerability endpoints are used to document potential harms observed during a study. They are important even when a study is not designed to estimate efficacy. However, an event occurring after treatment begins is not automatically caused by treatment. Attribution would require information and methods not described in the registry record. The primary endpoint is also not a measure of improvement in Charcot neuroarthropathy. The record does not report a primary efficacy endpoint or a result showing a change in the condition.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety data describe a single denosumab group. The record reports 0 participants with serious adverse events among 7 at risk, 2 participants with other adverse events among 7 at risk, and 0 deaths. These are descriptive counts, not estimates from a comparison between treatment groups. Because there is no comparator group, the data cannot show whether the frequency of events was higher or lower than it would have been under another treatment or no study treatment.
The zero count for serious adverse events means that no serious events were recorded in the reported group during the relevant observation. It does not establish that the underlying risk is zero. With a small enrolled group, observed event counts can be imprecise indicators of the event experience that might be seen in a broader population. A confidence interval, when reported, expresses uncertainty around an estimate; no confidence interval for these adverse-event counts is reported in the registry record. The absence of such an interval prevents a numerical description of that uncertainty using the registry’s posted results.
The 2 participants recorded with other adverse events provide a descriptive signal that such events were reported. The registry does not name these events, describe their severity, provide event-level timing, or state whether they were considered related to treatment. It is therefore not possible to characterize their clinical nature or attribute them to denosumab from this record. The serious and other event categories are reported separately, and the record does not establish whether they are mutually exclusive. They should not be combined to create a new overall count.
These results do not answer whether denosumab changes skin temperature or improves the underlying condition. The secondary outcome concerns change in skin temperature difference between the affected and non-affected limb at 6 months, but its results are not reported in the registry record. No analysis records are listed. The primary endpoint is safety-focused, and the registry summary describes the investigation as a pilot study of potential use. Neither the study title nor its completed status substitutes for an outcome analysis.
The design also constrains interpretation. Without a control group, differences over time cannot be separated from natural changes, concurrent care, measurement variation, or other influences. The record does not report participant-level baseline characteristics, follow-up completeness, event definitions, or statistical analyses that might further inform the counts. The appropriate reading is therefore narrow: the registry reports the stated counts in the treated group, while the precision, event attribution, comparative safety, and efficacy remain unresolved in this record.
9. Statistical Methods Explained
What does a participant count describe?
The primary outcome is defined in terms of participants with treatment-emergent adverse events. In general, a binary outcome classifies each participant according to whether the specified event occurred during the observation period. The reported count is a direct description of how many participants met that classification, while the number at risk identifies the group relevant to that count. The registry’s safety record gives counts for serious events, other events, and deaths. These should be read as distinct reported categories, not as event rates unless the record supplies an appropriate rate calculation and follow-up information.
Participant counts do not necessarily equal event episodes. A participant could experience more than one event, while a participant-level count records whether the person was affected under the relevant definition. The registry does not provide event-level detail or definitions sufficient to reconstruct episode counts. It also does not state whether serious and other events overlap at the participant level. For that reason, the listed counts should be interpreted within their reported categories rather than combined or expanded into unreported totals.
Why does uncertainty matter?
In general, a confidence interval gives a range of estimates compatible with the observed data under a specified statistical method. It communicates uncertainty that a single count or estimate cannot convey. For a binary safety outcome, the observed proportion can be unstable when the study group is small, especially when events are uncommon. A zero observed count does not mean that the underlying event probability is known to be zero. The registry record does not report a confidence interval or an inferential analysis for the safety counts, so the uncertainty cannot be quantified from the posted results.
The record’s reported counts are descriptive. A p-value would address a specified statistical hypothesis under a specified analysis, but no p-value or analysis record is listed. It would not be appropriate to infer a statistical test, a significance finding, or an adjusted estimate from the counts alone. The registry record does not report an analysis plan, adjustment strategy, or method for estimating treatment effects.
What does the single-group design allow?
In general, an uncontrolled single-group study can describe outcomes observed among participants receiving an intervention. A comparison against a concurrent control group is needed to estimate a between-group contrast within a trial. This study has no like-for-like control comparison: its model is single-group, allocation is recorded as not applicable, and masking is none. Thus, the posted event counts cannot be interpreted as a relative risk, risk difference, or other comparative treatment effect. No such quantities are reported in the registry record.
Masking, in general, can reduce the influence of expectations on outcome assessment or reporting. Here, the registry records no masking. That classification does not reveal how adverse events were collected or adjudicated, and the collection procedures are not reported in the registry record. The registry also does not state whether participants or investigators used a standardized event-reporting process.
What do the planning assumptions mean?
General sample-size planning uses assumptions about the outcome, the effect a study aims to detect, the significance level, allocation, and statistical model. The planning assumptions stated for this record specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial had a control arm. The actual study is single-group. Any sample-size illustration based on those assumptions is not an observed power calculation and should not be read as a result of the trial or as the study’s own design rationale. A sample-size justification is not reported in the registry record.
In general, a normal approximation simplifies calculations by approximating a sampling distribution with a normal distribution. Its suitability depends on the outcome and data structure. For sparse binary events, approximate methods can be less reliable than methods designed for small samples; however, the registry record does not state that a normal-approximation analysis was used for the adverse-event results. The planning assumptions alone do not establish the method used to analyze observed outcomes.
Over-dispersion is a general concern for count data when variability exceeds what a chosen model expects. It can make standard errors too small if the model does not allow for the extra variability. That issue should not be presumed to apply to these participant-level binary safety counts, and no over-dispersion model is reported. More broadly, no statistical analysis method for the posted adverse-event counts is reported in the registry record. Any method-specific interpretation beyond the descriptive counts would therefore be unsupported.
The secondary endpoint is a change in skin temperature difference, measured in degrees Celsius, between the affected and non-affected limb at 6 months. In general, a change endpoint compares a follow-up measurement with a baseline measurement, but the registry does not report the analysis definition, summary statistics, or result for this outcome. It is also not clear from the record whether the reported measure would be analyzed as a paired change or by another method. No such method should be assumed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures: the primary treatment-emergent adverse-event endpoint and the secondary skin-temperature endpoint. It lists 0 analysis records. Multiple outcomes can raise a multiplicity issue because testing several hypotheses may increase the chance of at least one false-positive finding if each is assessed separately. In general, a prespecified strategy may address this through a hierarchy, adjustment, or a clear distinction between primary and exploratory outcomes. No multiplicity strategy is reported in the registry record, and no inferential results are available to evaluate how such a strategy might have been applied.
Missing data can affect both the numerator and the population represented by an outcome. In general, interpretation depends on how many participants contributed data, when follow-up ended, and how missing observations were handled. The registry gives safety counts with participants at risk, but does not report follow-up completeness, withdrawal information, or a missing-data method. The result for the secondary skin-temperature outcome is not reported in the registry record, and the reason it is absent is not stated. It should not be assumed that there were no missing data or that all enrolled participants completed follow-up.
Analysis populations also matter. A trial may define groups such as all enrolled participants, all treated participants, or participants with observed outcome data, but the record does not identify an analysis population for the endpoints. It does not describe exclusions or how participants were handled if their treatment or follow-up differed from plan. Since no analysis records are listed, the population underlying any inferential analysis cannot be established from this record. The safety counts can be described as posted, but broader claims about analysis populations, missingness, or multiplicity are not supported.
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 |
|---|---|---|---|
| Intervention Group, Receiving Medication | 0 | 7 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Intervention Group, Receiving Medication | 0 of 7 |
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 |
|---|---|
| Intervention Group, Receiving Medication | 2 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Intervention Group, Receiving Medication |
|---|---|---|
| Muscle pain, upper extremity | Musculoskeletal and connective tissue disorders | 1 of 7 |
| Cellulitis | Infections and infestations | 1 of 7 |
The registry reports 0 participants with serious adverse events among 7 at risk, 2 participants with other adverse events among 7 at risk, and 0 deaths. These are the recorded safety counts for the intervention group. The serious-event count and other-event count are separate categories; the record does not establish whether they overlap. They should not be added to produce a combined count. It also does not name the other events or give event-level descriptions.
In general, an adverse event is an occurrence observed during a study, and its timing alone does not establish that the intervention caused it. The registry does not report attribution assessments, definitions, severity details for the other events, or the process used to collect and classify events. The counts therefore describe what was recorded, not a causal estimate of denosumab’s safety effect.
A zero count is not proof that the underlying risk is absent. It means no event in that category was recorded in this group, while uncertainty about the risk remains. The registry does not report confidence intervals or a comparative safety analysis. Because the study has a single group and no like-for-like control, the reported counts cannot establish how the event experience compares with another treatment or with no treatment.
12. What the Result Does, and Does Not, Mean
The result establishes a limited descriptive point: in this completed single-group study, the registry records 0 participants with serious adverse events among 7 at risk, 2 with other adverse events among 7 at risk, and 0 deaths. Those numbers describe the safety data as recorded. They do not establish that denosumab caused, prevented, or changed the likelihood of any event. The registry does not provide enough detail to characterize the other events or their relationship to treatment.
The record does not establish whether denosumab improves acute Charcot neuroarthropathy. The primary endpoint is safety and tolerability, not efficacy. Although the registry lists a secondary change in skin temperature difference between the affected and non-affected limb at 6 months, it does not report that outcome’s result. No analysis records are listed. A completed study status does not fill these gaps or imply that an outcome met a target.
The absence of a comparator is consequential. A single-group observation cannot separate treatment effects from the condition’s course, other care, or measurement and reporting influences. Even an observed change over time would not, by itself, identify what would have happened without the intervention. The record also lacks a reported statistical analysis, uncertainty interval, detailed event definitions, and participant-level information that could refine interpretation.
The pilot-study framing indicates that the investigation was intended to examine denosumab’s potential, but the registry does not report a sample-size justification. The enrollment and safety counts should not be taken as evidence of a precise safety estimate or a treatment effect. The cautious conclusion is that the registry documents the stated adverse-event counts in the intervention group, while comparative safety, efficacy, event attribution, and the temperature outcome remain unresolved in the registry record.
13. Why This Trial Matters Statistically
This study matters statistically because it illustrates the difference between a descriptive safety count and a comparative estimate. The record reports adverse-event experience among participants receiving denosumab, but its single-group design does not provide a concurrent control. As a result, the counts can describe what was observed without answering whether the intervention changed event risk. That distinction is central when reading safety results from uncontrolled studies.
The small enrolled group also makes precision an important consideration. In general, an observed count is only one realization of an uncertain process; sparse events can leave substantial uncertainty about the range of outcomes that might occur in a larger population. The registry record gives no confidence interval or inferential analysis for the adverse-event counts. The zero serious-event count should therefore be understood as an observation in this group, not as a precise estimate that serious events cannot occur.
The record also shows why endpoint definitions and analysis reporting matter. The primary outcome is described as treatment-emergent adverse events, while the posted safety information distinguishes serious from other events and reports deaths. The registry does not name the other events or explain the event-classification procedures. Without those details, readers cannot fully assess how the posted categories relate to the primary endpoint.
Finally, the registry lists a secondary temperature outcome but reports no result for it, and it lists no analysis records. This leaves the reader with a narrow safety description rather than a complete statistical evaluation of the study’s stated aims. The case emphasizes that design, endpoint reporting, uncertainty, and analysis transparency jointly determine what conclusions a trial record can support.
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 is the single-group design. The record contains no randomized or other like-for-like control group, so it cannot support a within-trial comparison of safety or efficacy. Allocation is listed as not applicable and masking as none. These design features limit causal interpretation and leave the possibility of influences unrelated to treatment unresolved.
Enrollment was 7. With a small study group, event counts can provide only limited information about uncommon outcomes and their precision. The registry does not report confidence intervals for the safety counts, so their uncertainty is not quantified. The absence of a serious event in the observed group should not be interpreted as evidence of no underlying risk.
The adverse-event reporting is limited. The record gives counts for serious events, other events, and deaths, but does not identify the other events, explain event definitions, provide timing or severity details, or report treatment attribution. It also does not state whether serious and other event categories overlap. These gaps prevent fuller characterization of the observed safety experience.
The registry lists a secondary skin-temperature outcome at 6 months, but its result is not reported in the registry record. No analysis records are listed, and no analysis methods, analysis population, missing-data approach, or multiplicity strategy are reported. The record does not provide a sample-size justification or detailed participant characteristics. These limitations restrict interpretation of both the study’s safety findings and its broader purpose of investigating denosumab for acute Charcot neuroarthropathy.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Investigating the Use of Prolia (Denosumab) in the Treatment of Acute Charcot Neuroarthropathy — NCT03174366.
- Registry record last updated 2019-10-23; status last verified 2019-10.
- Results first posted 2019-10-23.
- 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
NCT03174366 is a completed phase 3, single-group study sponsored by Western University of Health Sciences. It investigated denosumab for acute Charcot neuroarthropathy and enrolled 7 participants. The registry records no masking and no comparator group. The study began on 2017-05-16, with primary completion on 2018-06-18.
The primary endpoint is incidence of treatment-emergent adverse events for safety and tolerability over 1 year. The registry reports 0 participants with serious adverse events among 7 at risk, 2 with other adverse events among 7 at risk, and 0 deaths. It lists a secondary skin-temperature outcome at 6 months, but that result is not reported in the registry record. The record lists 2 outcome measures and 0 analysis records. The posted safety counts are descriptive; comparative effects, event attribution, and the secondary outcome remain unreported.