Investigation of Corticosteroid Versus Placebo Injection in Patients With Syndesmotic Ligament Injury or High Ankle Sprain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of Corticosteroid Versus Placebo Injection in Patients With Syndesmotic Ligament Injury or High Ankle Sprain (NCT02892500), a randomized phase 2 study. The primary outcome is Compare Between the Two Groups the Time to Return to Previous Levels of Activity.

2. Clinical Question

The trial was designed to compare two ultrasound-guided injection regimens in patients with syndesmotic ligament injury or high ankle sprain. Its primary question concerned the time needed to return to previous levels of activity, with a one-year timeframe. The registry also lists patient-reported foot and ankle ability as a secondary comparison. However, the record states that no participants were randomized and treated; it therefore contains no observed comparison of outcomes between the groups.

3. Trial Design

The registry describes a phase 2, randomized, parallel-group investigation at a single site. Its official title calls the study double blinded, while the masking classification in the record is quadruple. The record does not explain the difference between those descriptions or identify which roles were masked. It describes an ultrasound-guided injection in each group and names Sanford Health as the sponsor.

The intended comparison was between bupivacaine hydrochloride with betamethasone sodium phosphate and bupivacaine hydrochloride alone. For both groups, the arm descriptions say that a licensed provider under the direction of the principal investigator would use ultrasound to identify the inferior tibiofibular ligament. The injection provider was not to take part in follow-up visits or return assessments, according to the arm descriptions. Further details of allocation procedures, treatment delivery, or follow-up conduct are not reported in the registry record.

The registry lists enrollment as 1 and gives the study status as terminated. It also states that no participants were randomized and treated. These entries do not establish that the listed enrollment represents a treated or analyzed participant, and the record does not explain the enrollment entry. The recorded start is 2016-04 and primary completion is 2016-09-21. The intended primary outcome was time to return to previous levels of activity, assessed over one year; the listed secondary outcome compared Foot and Ankle Ability Measure results. No comparative outcome analysis is listed.

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.

Before assignment: No participants were randomized or treated during the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: No participants randomized and treated.

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.

Population: No participants were randomized or treated therefore no baseline characteristics were collected for this study.

6. Primary Endpoint

The registry lists the primary outcome as Compare Between the Two Groups the Time to Return to Previous Levels of Activity, measured over One year.

The primary endpoint is the time to return to previous levels of activity. In general, a time-to-event endpoint measures the interval between a defined starting point and the occurrence of a specified event. For this trial, the event is return to the participant’s previous activity level. Such an endpoint can describe not only whether an event occurs, but also how its timing differs between groups.

To interpret this measure, readers need a clear definition of the event and the time origin. For example, the record would need to specify what counted as previous activity and how return was assessed. Those operational details are not reported in the registry record. The timeframe is listed as one year, but the record does not give an endpoint unit, a summary parameter, or a dispersion measure.

The registry states that no participants were randomized and treated. It therefore gives no observed times to return, group-level summaries, or comparative estimate for this endpoint. The endpoint explains the question the study was designed to address, not a result about the relative timing of return in the two groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a randomized, parallel-group design. In general, random allocation is intended to make group assignment independent of participant characteristics, reducing the risk that those characteristics systematically determine which intervention a participant receives. A parallel design assigns each participant to one group for the comparison. These design labels describe the intended structure; they do not establish that allocation took place. In this trial, the registry states that no participants were randomized and treated.

What does masking mean?

In general, masking means keeping treatment assignment unknown to specified people involved in a study. This can reduce the influence of expectations on care, outcome assessment, or reporting. The record classifies masking as quadruple, while its official title says double blinded. It does not describe which people were meant to be masked, how masking was maintained, or how it might have been assessed. The difference between the two descriptions is not explained, so the masking procedures cannot be reconstructed from the registry record.

How should the primary endpoint be analyzed?

In general, time-to-event data require attention to when follow-up begins, how the event is defined, and whether each participant is observed through the event or leaves follow-up earlier. Some observations may be censored: the event has not been observed by the end of that participant’s available follow-up, but its later occurrence is unknown. Suitable methods account for the observed follow-up without treating an unobserved event time as if it were known. The record does not specify a time origin, censoring rules, a statistical method, or an effect measure for the return-to-activity endpoint. It also contains no outcome data to which such a method could be applied.

In general, a confidence interval gives a range of estimates compatible with the data under the method’s assumptions. Its width reflects precision: less precise data typically support a wider range of plausible values. A confidence interval is not a guarantee that the true effect lies within the interval, and it does not remove concerns about bias or study conduct. No confidence interval for the primary comparison is reported in this registry record.

What can a significance test establish?

In general, a significance test evaluates how compatible the data are with a specified null hypothesis under a statistical model. A p-value does not measure the size or clinical importance of an effect, and it cannot establish that a treatment works. Interpretation requires the estimated effect, its uncertainty, the analysis assumptions, and the study context. The registry lists no analysis for this trial, so it provides no comparative test result for the primary outcome.

The record’s sample-size assumptions describe planning illustrations using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the illustrated effect is a stated fraction of the observed effect; time-to-event illustrations use a total event count, and other illustrations use participants per arm. These are planning assumptions, not evidence of the trial’s planned enrollment or a reported analysis. The trial’s own sample-size justification is not reported in the registry record. No observed primary effect is available in the record on which to base an interpretation of those illustrations.

Why does over-dispersion matter in general?

For count outcomes, over-dispersion occurs when the variability in the data is greater than a model assumes. If ignored, the model may understate uncertainty and make estimates appear more precise than they are. Analysts may use methods that allow extra variability when the outcome and data support them. This is a general consideration, not a method reported for this trial: the registry does not identify a count outcome analysis or specify an approach for over-dispersion.

Finally, statistical methods depend on an analysis population and rules for handling missing measurements. A prespecified intention-to-treat analysis, for example, is intended to retain participants according to their randomized groups, while other analysis populations may use different inclusion criteria. No analysis population, missing-data procedure, or statistical analysis plan is reported in the registry record. With no participants randomized and treated and no listed analyses, those omissions leave no basis for assessing how an observed estimate would have been produced.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of time to return to previous levels of activity and a secondary outcome comparing Foot and Ankle Ability Measure results. It does not report a multiplicity strategy. In general, when researchers evaluate several outcomes or contrasts, the chance of finding at least one apparently unusual result can depend on how many tests are conducted. A prespecified hierarchy or adjustment can help clarify how multiple findings should be interpreted. The absence of a reported strategy does not establish that any particular adjustment was required or used.

Missing-data handling is not reported in the registry record. In general, incomplete outcome observations can reduce precision and may introduce bias if the reasons for missingness are related to outcome or group assignment. Appropriate interpretation depends on the amount and pattern of missingness, the assumptions used, and any sensitivity analyses. Here, the record states that no participants were randomized and treated, so it gives no treated-participant outcome observations from which to assess missingness or follow-up completeness.

The analysis population is also not reported. The record gives no statistical analysis plan or analysis-specific inclusion rules. Although enrollment is listed as 1, the registry states that no participants were randomized and treated; it does not explain the enrollment entry. The record lists no analyses. Thus, neither the intended analytic population nor the handling of any outcome data can be evaluated from the registry record.

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

The record documents a planned comparison of two injection regimens and identifies time to return to previous activity levels as the primary question. It does not document a comparative result. In particular, it provides no estimate of how return timing differed between groups and no measure of precision for such an estimate. The planned question and the evidence available to answer it are therefore distinct.

The absence of an analysis should not be interpreted as a finding of no difference. It also does not show that one regimen is better or worse, that the endpoint could not have been measured, or that the interventions caused no adverse events. The registry reports no participants randomized and treated, zero participants at risk in the adverse-event groups, and no analyses. Those entries describe the lack of an evaluable treated comparison, not a reassuring or unfavorable safety finding.

In general, a treatment effect estimate applies to the population, interventions, outcomes, and analysis that generated it. Because no estimate is reported, this record cannot quantify an effect, assess its clinical importance, or establish how precisely it was measured. It also cannot support conclusions about whether the findings would apply to other patients or settings.

The registry status is terminated, but the reason is not reported in the registry record. The enrollment entry of 1 does not resolve the stated absence of participants randomized and treated. Readers should therefore distinguish the study’s design and intended endpoint from observed evidence: the record describes what the trial set out to compare, but does not supply outcomes that answer the comparison.

12. Why This Trial Matters Statistically

This trial matters statistically because its planned question is clinically concrete, but the registry record does not contain the observations needed for a treatment comparison. A time-to-return endpoint can be meaningful only when the event is operationally defined, follow-up is described, and an analysis accounts appropriately for event timing and incomplete observation. The record identifies the endpoint and timeframe but does not report those analysis details or any outcome estimates.

The distinction between a planned design and an analyzed trial is important. Randomization and masking are design features intended to support a fair comparison, but they cannot substitute for observed outcomes. The registry describes randomized allocation and masking, yet also states that no participants were randomized and treated. The record’s enrollment entry does not establish that either injection group contributed outcome data.

The absence of results also illustrates why uncertainty must be separated from a null finding. Without an estimate and its precision, readers cannot assess the direction or size of a possible contrast. Zero adverse events with zero participants at risk likewise cannot be interpreted as evidence of safety. The registry record leaves the central comparative question unanswered rather than showing equivalence or no effect.

Finally, the record exposes limits on what registry design labels alone can establish. It gives different masking descriptions in the title and classification, does not report the analysis plan, and does not explain termination. These gaps do not prove a methodological problem, but they restrict assessment of how the intended comparison would have been implemented and interpreted.

13. 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 that the registry states no participants were randomized and treated, and lists no analyses. There are consequently no outcome estimates for the primary or secondary comparison. The reason the trial was terminated is not reported in the registry record, so the status cannot be linked to a particular operational or scientific cause.

The registry lists enrollment as 1, but does not explain this entry alongside the statement that no participants were randomized and treated. It is not possible to determine from the record whether that enrollment entry represents screening, registration, or another stage. It should not be treated as evidence of a treated or analyzed population.

The primary endpoint is named and its timeframe is given, but the record does not specify the time origin, operational definition of return to previous activity, outcome-assessment procedure, effect measure, or statistical method. It also does not report the analysis population, missing-data rules, or multiplicity handling. The stated sample-size assumptions are planning illustrations; the trial’s own sample-size justification is not reported in the registry record.

The official title describes the study as double blinded, while the masking classification says quadruple. The record does not explain which participants or study personnel were intended to be masked. It also identifies the trial as single-site, which limits the range of settings directly represented by the intended design, though no analyzed population is available to assess generalizability.

Adverse-event entries show zero participants at risk and zero events for both groups. With no participants randomized and treated, these entries cannot characterize harms among treated participants. The record provides no basis for resolving these limitations through outcome data or protocol details.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Investigation of Corticosteroid Versus Placebo Injection in Patients With Syndesmotic Ligament Injury or High Ankle Sprain — NCT02892500.
• Registry record last updated 2024-02-13; status last verified 2024-01.
• Results first posted 2020-11-02.
• 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.

17. Record Summary

The registry describes NCT02892500 as a phase 2, randomized, parallel, single-site investigation of ultrasound-guided injection for syndesmotic ligament injury or high ankle sprain. The intended groups were bupivacaine hydrochloride with betamethasone sodium phosphate and bupivacaine hydrochloride alone. The primary outcome was time to return to previous levels of activity over one year; the listed secondary outcome compared Foot and Ankle Ability Measure results.

The record lists Sanford Health as sponsor, status as terminated, enrollment as 1, and primary completion as 2016-09-21. It also states that no participants were randomized and treated and lists no analyses. No comparative outcome estimate is reported. The reason for termination, trial-specific analysis plan, and explanation of the enrollment entry are not reported in the registry record.