Platelet Rich Plasma Injection in Pilon Fractures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Platelet Rich Plasma Injection in Pilon Fractures (NCT02481869), a randomized na study. The primary outcome is Intra-articular Inflammatory Biomarkers at the Time of Definitive Fixation.

2. Clinical Question

The trial’s official question also asks whether early PRP decreases the risk of post-traumatic arthritis in pilon fractures. The listed primary outcome, however, is inflammatory biomarkers at definitive fixation, rather than an arthritis diagnosis or arthritis-risk measure. Biomarkers are being used to assess inflammation in the joint; they are not themselves a direct measure of later arthritis or patient experience.

The registry lists patient-reported outcomes among secondary outcomes, including the Ankle-Hindfoot Scale (AOFAS), Short Form Health Survey (SF-12), and Visual Analog Scale (VAS). Numerical results for these outcomes are not reported in the registry record. The record therefore describes the question and planned outcome domains, but it does not provide results that answer whether biomarker levels differed between the assigned groups or whether later arthritis differed.

3. Trial Design

This was a randomized, single-masked, parallel-group trial. The registry lists 11 participants enrolled and describes two interventions: arthrocentesis with PRP and arthrocentesis with saline. Random allocation means assignment to the intervention groups was intended to occur by chance. The record does not report the allocation method or how the random sequence was generated.

Single masking indicates that the registry identifies one masking level, but it does not identify who was masked. The identity of the masked party is not reported in the registry record. The parallel model means the record describes participants assigned to one intervention group rather than a crossover design.

The intervention descriptions place the injection at surgery. In each description, the injured and uninjured ankles are cleaned, synovial fluid is drawn from the injured ankle joint, and the assigned substance is delivered using the same needle. The available descriptions end before giving a complete account of the injection procedure, so further procedural details are not reported in the registry record.

The registry identifies the study as completed. Its listed dates are a start in 2015-06 and primary completion in 2019-11. The phase is recorded as NA. These record details describe the study’s design and status; they do not establish whether its planned comparisons were completed or how participants were analyzed. The analysis count is listed as 0, and the primary outcome has not been reduced to a single comparison because it has several categories or time points. Numerical primary outcome results are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Plan for total enrollment of n=40 with n=20 in the PRP arm and n=20 in the saline arm

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 Intra-articular Inflammatory Biomarkers at the Time of Definitive Fixation, measured over 2 weeks after external fixation.

The primary endpoint is titled “Intra-articular Inflammatory Biomarkers at the Time of Definitive Fixation.” It measures inflammatory biomarkers in the ankle joint, with units of pg/ml. The registry describes the measure as a mean with standard deviation and gives the timeframe as 2 weeks after external fixation, at definitive fixation.

Joint biomarkers can serve as measures of biological processes associated with inflammation. In this trial, they provide a way to examine a biological response after injury and injection. In general, a biomarker endpoint is not equivalent to a clinical outcome: a difference in a laboratory measure would not by itself establish a difference in pain, function, or later post-traumatic arthritis.

The registry does not identify the biomarker names, the number of categories or time points, or numerical group results. The record notes that the primary outcome has several categories or time points and was not reduced to one comparison. It therefore does not support a specific estimate of the PRP-versus-saline contrast, its uncertainty, or its statistical significance. The stated endpoint and timing define what was intended to be measured, but without numerical results they cannot show the direction or precision of any group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

General: A mean is the arithmetic average of measured values. It can describe the center of a continuous outcome, such as a biomarker concentration. It does not show how individual measurements are distributed, and it can be influenced by unusually high or low values. The registry specifies a mean and standard deviation for the primary endpoint, but does not report the observed means or standard deviations.

What does a standard deviation describe?

General: A standard deviation describes the spread of measurements around their mean. It is a measure of variability among observations, not the precision of the estimated mean and not a confidence interval. The standard deviations for the biomarker groups are not reported in the registry record, so the amount of observed variability cannot be assessed.

Why does the unit matter?

The primary outcome is expressed in pg/ml. Units make clear that the endpoint is a concentration measure and are essential when interpreting a numerical value or comparing measurements. The registry record does not identify the biomarkers or give their measured concentrations. Therefore, the scale and biological interpretation of any particular biomarker result cannot be discussed from the record.

How should a group comparison be read?

General: A comparison of group means describes the observed difference between average measurements in the assigned groups. A confidence interval, when reported, gives a range of values compatible with the data and the statistical procedure used. Its width conveys precision: a wider interval indicates less precise estimation than a narrower one. A confidence interval does not show the probability that a particular value is true.

No group means, between-group estimate, or confidence interval for the primary endpoint is reported in the registry record. The record also indicates that the primary endpoint has several categories or time points, rather than one reduced comparison. Without a specified comparison and its results, readers cannot determine which time point or category an estimate would describe, or how uncertain it would be.

What does randomization contribute?

General: Random assignment is intended to reduce systematic differences between groups at the point of assignment. It does not guarantee that groups will be similar in every characteristic, especially in a small study. Randomization also does not eliminate the need to report how allocation was generated, how participants were handled after assignment, and which analyses were conducted. The registry identifies the study as randomized but does not report the sequence-generation method or an analysis population.

What does masking tell readers?

The study is listed as single-masked. In general, masking can reduce the influence of knowledge of treatment assignment on some aspects of trial conduct or outcome assessment. The registry does not identify who was masked or describe how masking was maintained. This prevents a more specific assessment of the masking procedure from the record alone.

What are the planning illustrations?

The registry describes sample-size planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. The illustrations are planning scenarios, not evidence about the trial’s actual power and not observed results. They must not be interpreted as “observed power.” The record does not provide numerical planning values in the registry record for this analysis.

General: A sample-size calculation estimates how many participants might be needed under stated assumptions to detect an effect using a specified statistical approach. Its conclusions depend on those assumptions, including the effect size and variability. A planning illustration based on an observed effect is not a substitute for a prespecified design justification, and the trial’s own sample-size justification is not reported in the registry record.

Why can over-dispersion matter?

General: Over-dispersion occurs when outcome variability is greater than a statistical model assumes. If a model underestimates variability, its uncertainty estimates can be too small and its intervals too narrow. The primary outcome is described as a continuous measure summarized with a mean and standard deviation; the registry record does not report a model or enough numerical results to assess over-dispersion. It would not be appropriate to assume that a particular correction was used.

What can be concluded from the posted analysis details?

The record lists 0 analyses and does not provide numerical primary outcome findings. It does not report the statistical test, model, adjustment variables, missing-data method, or analysis population. These details are not reported in the registry record. Accordingly, the intended endpoint and design can be described, but the statistical evidence for a PRP-versus-saline difference cannot be reconstructed from these details.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is described as having several categories or time points, and the record explicitly indicates that it was not reduced to one comparison. When a study examines multiple outcomes, time points, or categories, the chance of observing at least one apparently notable result can increase if each is tested separately. General approaches to multiplicity include prespecifying a primary comparison or adjusting inference across tests. The registry record does not report a multiplicity procedure, a hierarchy of tests, or which comparison was intended to be primary among the categories or time points.

The record lists 7 outcome measures and identifies patient-reported outcomes among the secondary outcomes. It does not report which analyses were conducted for these measures. The analysis count is 0. Numerical outcome results, p-values, and confidence intervals are not reported in the registry record, so neither the extent of multiplicity in the analyses nor its handling can be evaluated.

Missing-data counts and methods are not reported in the registry record. It is not possible to tell whether all enrolled participants contributed primary outcome data, whether any measurements were unavailable, or how any missing values were handled. The analysis population is also not reported: the record does not identify whether results would be based on participants as randomized, those who received the assigned procedure, or another group.

These omissions matter because the interpretation of an estimate depends on which participants and measurements were included and how multiple comparisons were treated. They do not establish that data were missing or that multiplicity was mishandled; the relevant details are simply not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infection (40.0%), hardware loosening (20.0%), painful implants (20.0%).

The registry reports serious adverse event figures separately for PRP and saline. For PRP, 5 participants were at risk and 4 were affected by serious adverse events; for saline, 6 were at risk and 0 were affected. The record lists 0 deaths in each group. For other adverse events, 1 participant was affected in each group, with 5 at risk in PRP and 6 in saline.

These are counts, not adjusted comparisons or estimates of causal effect. The registry record does not report event timing, participant-level details, exposure duration, or whether events were judged related to the assigned intervention. It also does not report statistical uncertainty around the counts. With the reported numbers, the figures describe what was recorded but do not establish why an event occurred or how reliably the groups’ underlying risks can be compared.

The record lists Infection, Hardware Loosening, and Painful Implants among the top serious-event terms, with percentages of 40.0%, 20.0%, and 20.0%, respectively. It does not specify in the available details how those percentages were calculated or connect each term to a particular intervention group. They should therefore be read as listed event terms and percentages, not as group-specific risk estimates.

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

The registry record establishes that a randomized, single-masked, parallel trial compared PRP injection with saline injection in people with pilon fractures, and that it enrolled 11 participants. It identifies intra-articular inflammatory biomarkers at definitive fixation as the primary endpoint, with the measurement described in pg/ml and summarized as a mean and standard deviation. These are design and outcome specifications, not evidence of a treatment effect.

Numerical results for the primary outcome are not reported in the registry record. The record says the outcome has several categories or time points and was not reduced to one comparison, and it lists 0 analyses. Therefore, readers cannot determine whether biomarker measurements differed between groups, how large any difference was, or how precisely it was estimated. The record also does not provide numerical patient-reported outcome results or an arthritis outcome result.

The posted adverse-event counts document serious and other events in each group, as well as deaths. They do not by themselves establish that an intervention caused or prevented an event. Event-level detail and comparative uncertainty are not reported in the registry record.

In general, biological markers can help describe a process in tissue, but a biomarker result is not interchangeable with a patient-centered outcome or later diagnosis. A difference in biomarkers, if reported, would need to be interpreted alongside its uncertainty and the clinical outcomes relevant to the trial’s official question. Here, the record does not include the numerical findings needed for those judgments.

Thus, the registry entry describes a clinical question and trial design but does not provide enough outcome evidence to determine what the comparison found. This is a limitation of what is reported in the registry record; it is not proof that no analyses or other results exist elsewhere.

13. Why This Trial Matters Statistically

This trial raises a statistical distinction between a biological endpoint and a clinical question. Its official title asks whether early PRP decreases the risk of post-traumatic arthritis, while its listed primary endpoint is intra-articular inflammatory biomarkers at definitive fixation. Biomarkers can be informative about inflammation, but they do not directly measure later arthritis, pain, or function. Statistical interpretation must follow the endpoint that was actually measured and reported.

The record also highlights the importance of reporting a clear primary comparison when an endpoint has several categories or time points. Without a stated comparison, numerical estimate, and uncertainty measure, readers cannot assess the direction, size, or precision of a result. This is especially relevant when multiple outcomes and time points are listed, because transparent analysis plans help readers distinguish a primary inference from exploratory comparisons.

The trial’s enrollment of 11 and the sparse safety counts make careful description important. Counts show what the registry records, but they do not on their own yield precise comparative conclusions. Uncertainty, event definitions, timing, and analysis populations are relevant to interpreting both efficacy and safety findings.

Finally, the record’s listing of planning illustrations should not be confused with observed power or with evidence that an effect was detected. Sample-size scenarios depend on assumptions and serve as planning aids. In the absence of numerical outcome analyses, the key statistical contribution of this record is to define the intended comparison and expose what information is needed for a reliable interpretation: outcome estimates, uncertainty, analysis details, and transparent handling of multiple outcomes and missing data.

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 main limitation for interpreting this trial from the registry record is the absence of numerical primary outcome results. Although the record identifies the biomarker measure, unit, summary statistic, and timeframe, it does not give group values or a between-group estimate. It also states that the endpoint includes several categories or time points and is not reduced to one comparison. This prevents assessment of effect direction, magnitude, and precision.

The record lists 0 analyses, and statistical methods for the outcome comparisons are not reported in the registry record. The analysis population, handling of missing data, and multiplicity approach are also not reported. These omissions limit the ability to evaluate how the intended comparison was carried out; they do not establish that a particular method was or was not used outside the record.

The trial is described as single-masked, but the identity of the masked party and the masking procedures are not reported. The randomization method is likewise not reported. Eligibility criteria, participant characteristics, biomarker identities, and detailed intervention procedures are not reported in the registry record, which limits assessment of applicability and reproducibility.

The available safety information consists of group counts and listed event terms. Details such as timing, duration of observation, participant-level event histories, and attribution are not reported. The serious-event percentages are listed without enough detail in the available record to interpret their calculation or assign them to a specific group.

Finally, the listed secondary outcomes include patient-reported measures, but their numerical results are not reported in the registry record. The official question concerns post-traumatic arthritis, while no numerical arthritis result is listed. These limitations restrict conclusions to the trial’s design and the descriptive safety figures that are recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Platelet Rich Plasma Injection in Pilon Fractures — NCT02481869.
• Registry record last updated 2021-02-05; status last verified 2021-01.
• Results first posted 2021-02-05.
• 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

NCT02481869 is a completed, randomized, single-masked, parallel trial titled “Platelet Rich Plasma Injection in Pilon Fractures.” The registry lists enrollment of 11 and compares arthrocentesis with PRP against arthrocentesis with saline in pilon fractures undergoing two-staged open reduction with internal fixation.

The primary endpoint is intra-articular inflammatory biomarkers at definitive fixation, described as a mean with standard deviation in pg/ml at 2 weeks after external fixation. The record states that the primary outcome has several categories or time points and was not reduced to one comparison. It lists 7 outcome measures and 0 analyses.

Numerical primary and secondary outcome results, analysis methods, analysis populations, and missing-data procedures are not reported in the registry record. Serious adverse events affected 4 participants in the PRP group and 0 in the saline group; other adverse events affected 1 participant in each group, and deaths are recorded as 0 in each group. These counts are descriptive and do not establish causation.