Effect of Febuxostat on Joint Damage in Hyperuricemic Subjects With Early Gout: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Febuxostat on Joint Damage in Hyperuricemic Subjects With Early Gout (NCT01078389), a randomized phase 2 study. The primary outcome is Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 2 study comparing febuxostat with placebo in people with elevated serum urate and early gout. The registry record lists enrollment of 314. It describes quadruple masking and identifies the study as completed. The start was recorded as 2010-03 and primary completion as 2013-09.

Participants assigned to febuxostat received capsules orally once daily for up to 24 Months. The dose was 40 mg or 80 mg based on serum urate levels at Day 14. The comparator group received placebo-matching capsules on the same once-daily schedule, also for up to 24 Months. These descriptions establish the intended treatment contrast, but the record does not provide further detail about adherence, treatment changes, or the number of participants who completed follow-up.

The study’s stated purpose was to assess the effect of once-daily febuxostat on joint damage. The primary outcome focused on the modified Sharp/van der Heijde erosion score for a single affected joint. Other listed outcomes included imaging-based measures of total scores and erosion scores from full hands and feet radiographs, a RAMRIS score for the single affected joint, and a total score for that joint.

The record does not report the rationale for the enrollment target, details of sequence generation or allocation concealment, or a full statistical analysis plan. It also does not provide the primary outcome’s numerical results. The design features alone cannot show whether the groups differed in joint damage or how precisely any difference was estimated.

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: Participants with a diagnosis of gout were enrolled equally in 1 of 2 treatment groups, once a day placebo or febuxostat 40 mg or 80 mg based on serum urate levels.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set included all randomized participants who received at least one dose of study medication. Participants were analyzed according to the treatment group to which they actually received. Participants with data available for analysis and missing values at Month 24 imputed using linear extrapolation are included in the analysis.

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 Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint, measured over Baseline and Month 24.

The primary endpoint was mean change from baseline to Month 24 in the modified Sharp/van der Heijde erosion score of the single affected joint. That joint was defined as the joint with the history of the first acute gout flare. Radiographs of the joint in the hands or feet were assessed using the modified Sharp/van der Heijde method.

Each erosion was scored on a scale from 0, meaning no erosion, to 3, meaning a large erosion passing the mid-line. The component erosion scores were summed. The maximum erosion score was 5 for joints in the hands and 10 for joints in the feet. Higher scores indicated more joint damage; a negative change from baseline indicated improvement. These are properties of the measurement, not evidence of a treatment effect.

In general, an imaging score can provide a structured way to quantify joint changes over time, rather than relying only on a broad clinical impression. The single-joint definition also ties assessment to the joint associated with the first acute gout flare. However, interpreting the endpoint requires the observed group results, their variability, and an estimate of the between-group contrast. Those numerical results are not reported in the registry record, so the magnitude and precision of the primary comparison cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean change represent?

The endpoint is a continuous score, and the registry record identifies the parameter as a mean. In general, a mean change describes the average difference between measurements at the start of follow-up and the specified later assessment within a group. Comparing those average changes between treatment groups addresses whether their average trajectories differed over that interval. The endpoint is specifically the change from baseline to Month 24, not a comparison of all possible changes over time.

The direction of the score matters. Higher erosion scores indicate more joint damage, and a negative change from baseline indicates improvement. A mean alone does not describe how individual measurements vary around it. The record identifies standard deviation as the dispersion measure, which in general describes the spread of observations around a mean. The primary result values for the mean and standard deviation are not reported in the registry record.

What would a treatment contrast tell the reader?

In general, a between-group contrast in mean change would express how far apart the average changes were for febuxostat and placebo. The estimate would be interpreted in the score’s units and direction. Its uncertainty would matter: a confidence interval, if reported, would show a range of values compatible with the data and the method used to calculate it. A narrow interval would indicate greater precision than a wide interval, while neither interval width nor statistical significance alone determines clinical importance.

The registry record does not report a numerical contrast or confidence interval for the primary endpoint. It also does not report a p-value for that endpoint in the registry entries. Therefore, no treatment-effect estimate, precision assessment, or significance interpretation can be made from the posted results. In general, a p-value is a measure tied to a specified statistical model and null hypothesis; it is not the probability that a treatment works or that the null hypothesis is true.

Why can variation and distribution matter?

General statistical considerations apply to continuous scores. When measurements vary substantially among participants, a group mean may conceal a range of individual changes. Distributional shape can also affect how well a chosen model describes the data. If the analysis uses a method that assumes a particular distribution or variance structure, departures from those assumptions can affect standard errors and inferential conclusions. The primary analysis method and diagnostic checks are not reported in the registry record, so it is not possible to say which assumptions were used or assessed.

Over-dispersion is a general concern when observed variability is greater than a model allows. In that situation, standard errors can be too small if the model does not account for the extra variation, which can make uncertainty appear less than it is. This is a general methodological point, not a claim that over-dispersion occurred in this trial. The record names standard deviation as the dispersion measure but does not give the observed values or describe a model for the primary comparison.

What can be inferred from the analysis population?

The stated Full Analysis Set included all randomized participants who received at least one dose of study medication. Participants were analyzed according to the treatment group they actually received. In general, analysis populations define which participants contribute to a result and how their treatment exposure is classified; these choices affect the interpretation of a comparison. The record's wording differs from a simple statement that all randomized participants were analyzed according to assignment, so it is important not to assume that convention was used.

The population description also says participants with data available for analysis and missing values at Month 24 were imputed using “linear ex” before the description cuts off. The complete imputation method is not reported in the registry record. Without the full method, assumptions, and amount of missing data, readers cannot assess how missing endpoint measurements were handled or how sensitive the result might be to that handling.

What do planning illustrations mean?

In general, sample-size planning asks how much information a proposed study might need to detect a chosen effect under stated assumptions. The registry record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Such illustrations are planning calculations, not observed power and not a description of the study's original sample-size justification. The record does not report that justification. A planning calculation also cannot recover a missing treatment estimate or establish the outcome result.

The analysis method, model specification, handling of multiple outcomes, and any interim analyses are not reported in the registry record. General explanations of means, uncertainty, assumptions, and planning therefore should not be mistaken for the statistical procedure actually used for this endpoint.

10. Multiplicity, Missing Data and Analysis Populations

The record lists five outcome measures and seven analyses. The primary outcome is described as having several categories or time points and is not reduced to one comparison. The numerical primary results are not reported in the registry record. The listed secondary outcomes cover full hands and feet radiographs, erosion and total scores, and MRI scoring of the single affected joint, but their numerical estimates are also not included in the registry entries.

In general, evaluating multiple outcomes or multiple comparisons raises a multiplicity issue: the chance of at least one apparently unusual result can increase when many tests are conducted. Statistical plans may address this through a prespecified hierarchy, adjustment, or other strategy. The registry record does not report whether any such strategy was used, which analyses were primary or supportive beyond the named primary endpoint, or how interpretation across outcomes was controlled. It would be inappropriate to assume either that adjustment was used or that it was not used.

The analysis population is described as randomized participants who received at least one dose, analyzed according to the group actually received. The record says missing Month 24 values were imputed using a phrase beginning “linear ex,” but the method is truncated. The amount and pattern of missing data, assumptions behind imputation, and sensitivity analyses are not reported in the registry record. Those details matter because conclusions from a longitudinal endpoint can depend on how unavailable measurements are treated.

The record also does not report the full statistical analysis plan or interim analyses. Without those details and the numerical results, it is not possible to assess how multiplicity, missingness, or analysis-population choices affected the primary inference.

11. Safety Results

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

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: dyspnoea (1.3%), cardiac failure congestive (0.6%), acute myocardial infarction (0.6%), angina pectoris (0.6%), mitral valve incompetence (0.6%).

The registry record reports serious adverse events for the febuxostat 40 mg or 80 mg group as 13 affected among 157 at risk, and for the placebo group as 11 affected among 157 at risk. It also reports other adverse events as 73 affected among 157 at risk in the febuxostat group and 67 affected among 157 at risk in the placebo group. These are reported counts and denominators; no percentages are calculated.

Serious adverse event terms listed include Dyspnoea at 1.3%, Cardiac failure congestive at 0.6%, Acute myocardial infarction at 0.6%, Angina pectoris at 0.6%, Mitral valve incompetence at 0.6%, and Left ventricular dysfunction at 0.6%. The record does not assign these term-specific percentages to a treatment group in the registry entries, so they should not be attributed to either group.

These safety figures do not by themselves establish comparative risk. The registry record does not provide event timing, recurrent-event details, definitions beyond the serious/other categories, or death counts. Death data are not reported in the registry record.

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

The registry record establishes that a randomized, masked, parallel-group phase 2 study compared once-daily febuxostat with matching placebo in people with elevated serum urate and early gout. It specifies a primary imaging outcome, its assessment time, the score’s direction, and the stated analysis population. These design and measurement details clarify what the study intended to examine.

They do not establish what the primary endpoint showed. No numerical mean changes, between-group estimate, standard deviation, confidence interval, or p-value for the primary comparison are reported in the available registry information. The absence of those values is not evidence of no difference, nor is it evidence of a difference. It leaves the direction, magnitude, and precision of the comparison unknown from the registry record.

Likewise, the listed secondary outcomes cannot be interpreted as findings without their numerical results. A named outcome indicates what was assessed, not what the assessment found. The serious and other adverse event counts are descriptive safety information, but the available details do not support a complete evaluation of comparative safety or event timing.

In general, a statistically detectable difference and a clinically meaningful difference are not interchangeable concepts. Statistical inference concerns compatibility of observed data with a model and a specified hypothesis; clinical meaning depends on the size and relevance of the change in context. The score description supplies direction and scale characteristics, but no observed treatment contrast is available to interpret either statistically or clinically.

The sample-size planning description should also be kept separate from a trial result. Planning illustrations are not observed power, and they do not substitute for a reported effect estimate. The record does not provide the original sample-size justification. Overall, the posted information describes the question and some design features, but does not provide enough primary outcome data to determine the result of that question.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a clearly defined endpoint and a reportable result. The endpoint is described in operational terms: a specified affected joint, an imaging-based erosion score, an assessment from baseline to Month 24, and a direction in which higher values indicate more damage. Those details make the intended measurement easier to understand and help readers identify what an eventual estimate would mean.

At the same time, outcome definition cannot replace outcome reporting. Without the numerical group results and a between-group estimate with uncertainty, readers cannot judge the size or precision of the primary comparison. This illustrates why a registry record’s design details and outcome definitions should be distinguished from evidence about the observed result.

The study also raises general issues that matter in longitudinal imaging analyses: the role of measurement variability, the definition of an analysis population, missing follow-up values, and interpretation across multiple outcomes. The registry record provides some information about each of these areas, but the imputation description is truncated and the multiplicity strategy and primary analysis method are not reported. These omissions limit scrutiny of how the endpoint was analyzed.

Finally, planning calculations and observed results answer different questions. A planning illustration depends on assumptions about an effect and analysis; it is not a measure of how much power the completed study actually had. This distinction is important when registry results are incomplete. The record can support a description of the trial’s question and design, but not a conclusion about the primary treatment contrast.

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 for interpreting this trial from the registry record is that numerical primary outcome results are not reported. The record does not provide the group mean changes, standard deviations, treatment contrast, confidence interval, or p-value needed to assess the primary comparison. The skip note indicates that the primary outcome has several categories or time points and was not reduced to one comparison, further limiting a concise numerical interpretation.

The analysis-population description is incomplete at the point where it describes imputation: it ends after “linear ex”. The complete missing-data method, the extent of missingness, and any sensitivity analyses are not reported in the registry record. The record also does not describe the primary statistical model, assumptions or diagnostics, multiplicity strategy, interim analyses, or the original sample-size justification.

The available safety information is limited to counts for serious and other adverse events and a list of serious event terms with percentages. The term-specific percentages are not assigned to an arm in the registry entries. Event timing and death counts are not reported in the registry record.

These limitations concern what can be evaluated from the registry information. They do not establish that an analysis was not performed or that a result was absent from other reporting. They mean that the posted registry entries alone do not support a complete assessment of the primary treatment effect, its precision, or the robustness of its analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Febuxostat on Joint Damage in Hyperuricemic Subjects With Early Gout — NCT01078389.
• Registry record last updated 2014-09-10; status last verified 2014-09.
• Results first posted 2014-09-10.
• 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

NCT01078389 is a completed randomized, quadruple-masked, parallel-group phase 2 study of febuxostat versus placebo for joint damage in people with elevated serum urate and early gout. Enrollment was 314. Febuxostat was given orally once daily at 40 mg or 80 mg based on serum urate levels at Day 14; placebo-matching capsules were given once daily for up to 24 Months.

The primary endpoint was mean change from baseline to Month 24 in the modified Sharp/van der Heijde erosion score of the single affected joint. The registry record describes the score and the Full Analysis Set but does not report the numerical primary outcome comparison. The description of imputation for missing Month 24 values is truncated. Serious and other adverse event counts are reported, while further safety details are limited. As a result, the registry record identifies the study question and selected design features but does not permit assessment of the magnitude or precision of the primary treatment contrast.