Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome (NCT01654276), a na phase 4 study. The primary outcome is BMI.

2. Clinical Question

3. Trial Design

This is a phase 4, single-group study of febuxostat in adults with gout and hyperuricemia. The registry lists enrollment of 24 and identifies the University of Texas Southwestern Medical Center as sponsor. The recorded start is 2012-05, primary completion is 2015-03, and status is completed. These are registry entries; the record does not give further information about the conduct or timing of individual assessments.

The described population consists of adults older than 21 years with gout who require uric-acid-lowering therapy and meet sex-specific serum uric acid criteria: greater than 7.0 mg/dl in men and greater than 6.0 mg/dl in women. The study summary identifies febuxostat as the drug under evaluation. It describes interest in insulin resistance, high blood pressure, elevated insulin levels, excess body fat around the waist, and high cholesterol. The listed primary outcome, however, is BMI at 6 months.

The record identifies the model as single-group, allocation as not applicable, and masking as none. It therefore does not describe random assignment or a masked control comparison. The registry record does not report a comparator, dose, treatment schedule, co-interventions, protocol deviations, adherence, or the exact assessment schedule beyond the primary outcome timeframe. These omissions limit what can be inferred about how treatment was delivered and how measurements were obtained.

The record lists 15 outcome measures and 1 analysis, but detailed analysis methods and numerical primary-outcome results are not reported in the registry record. In particular, it is not possible from the posted information to determine whether the BMI result represents an endpoint value, a change from baseline, or another summary. A single-group design can describe outcomes within the studied group, but without a concurrent like-for-like control it does not provide the same protection against alternative explanations as a randomized comparison.

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

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 BMI, measured over 6 months.

The primary endpoint is BMI, reported as a mean with standard deviation and measured in kg/m^2 at 6 months. BMI expresses body mass relative to height and is commonly used as a broad measure related to body size. It is practical for summarizing a continuous outcome across a group, and the mean describes the group’s average while the standard deviation describes the spread of individual measurements around that average.

As a general statistical point, BMI is not a direct measurement of body fat or its distribution. It does not by itself describe waist circumference, insulin resistance, blood pressure, insulin levels, or cholesterol. Those features appear in the study’s stated rationale, but their presence in the summary does not establish that they were primary outcomes or that their results are available. The primary endpoint specifically listed in the registry is BMI.

The timeframe is 6 months, but the numerical mean and standard deviation are not reported in the registry record. Nor does the record specify whether the mean refers to BMI at that timepoint, a change from baseline, or another calculated quantity. Without those details and the outcome values, the magnitude, direction, and precision of the primary result cannot be assessed. The endpoint definition alone describes what was intended to be measured; it is not evidence of an observed effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary outcome summarized by a mean and standard deviation. As a general statistical explanation, a mean represents the arithmetic average of measured values, while a standard deviation describes how dispersed those values are around the mean. These summaries answer different questions: the mean locates the group average, and the standard deviation describes variation among measurements. Neither quantity is available numerically for BMI in the registry record.

What does a continuous endpoint mean?

A continuous measure can take a range of values rather than representing only a category or event count. BMI, listed in kg/m^2, is treated as continuous in this record. Analyses of continuous outcomes commonly estimate a mean or a difference in means, but the exact estimand and calculation depend on the analysis plan. The registry does not report whether the primary endpoint is an endpoint mean, a mean change from baseline, or another summary. It also does not report the analysis population, treatment of repeated measurements, or adjustment variables.

In general, a standard deviation is not the same as a standard error or a confidence interval. The standard deviation describes variation in individual observations. A standard error describes uncertainty in an estimated quantity under a statistical model, and a confidence interval expresses uncertainty around an estimate. These quantities are not interchangeable. Because the registry has no numerical BMI summary or interval estimate, neither observed variability nor precision of an estimated BMI effect can be reviewed.

What does the single-group design allow?

The design is listed as single-group, with allocation not applicable and no masking. In general, a single-group study can report measurements observed in the participants who receive the study intervention. If measurements are taken at more than one time, a within-group change may be calculated, but the record does not establish that the primary result is such a change. Even when a before-and-after difference is available, it is not the same as a randomized comparison against a concurrent control. Time trends, other care, participant characteristics, and measurement processes can also influence observed outcomes.

A randomized comparison generally uses allocation to create groups that can be compared under stated assumptions. No such comparator is recorded for this study. Thus any two-arm planning illustration associated with the posted material should not be interpreted as the design actually used. The registry lists no like-for-like control arm, so a between-group treatment effect cannot be obtained from the design description alone.

How should uncertainty and significance be understood?

As general concepts, a confidence interval helps communicate both the estimated effect and the range of values that remain compatible with the data and model. A p-value evaluates how surprising data would be under a specified null hypothesis and assumptions; it does not measure the probability that a hypothesis is true, nor does it measure clinical importance. Neither a p-value nor a confidence interval for the primary BMI result is reported in the registry record. No significance threshold or test procedure for the primary endpoint is reported either.

The record’s general planning assumptions mention a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation for a planning illustration based on a fraction of an observed effect. Those assumptions describe an illustration, not a reported analysis of this single-group study. No numerical planning estimates are stated in the registry entries. Such planning quantities are not observed power, do not indicate how likely the study was to detect a true effect, and do not replace an analysis of the observed outcome.

Why can over-dispersion matter?

As a general concept, over-dispersion arises when count data vary more than a model assumes. If present, a model that understates variability can make uncertainty look too small. This issue is most relevant to count or event outcomes, not automatically to a continuous mean such as BMI. The registry’s listed primary endpoint is continuous, and the record does not report an over-dispersion assessment or a count-data model. It would not be appropriate to claim that over-dispersion was present or that a particular correction was used.

More broadly, reliable interpretation depends on the match between the statistical model, the outcome distribution, the estimand, and the design. For a mean outcome, assumptions may concern how observations vary and how missing measurements are handled. For event outcomes, assumptions may concern event definitions and follow-up. The registry record does not provide enough statistical detail to assess those assumptions for this study.

What do the listed analysis counts tell us?

The registry lists 15 outcome measures and 1 analysis. These counts do not specify which outcomes were analyzed, the hypotheses tested, the analysis population, or whether the listed analysis pertains to the primary outcome. The numerical results and detailed procedures are not reported in the registry record. A count of measures or analyses cannot substitute for the estimates, uncertainty intervals, and methods needed to evaluate a finding.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Gout and Hyperuricemia")
n   <- c(18)
m   <- c(33.4)
sp  <- c(5.9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Gout and Hyperuricemia  18  33.400  5.900  30.466  36.334

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 1 analysis, but does not identify a multiplicity strategy. Multiplicity refers, in general, to the increased chance of finding at least one apparently notable result when many outcomes or hypotheses are examined. Possible approaches include defining a primary endpoint in advance, adjusting inference across a family of tests, or treating secondary analyses as exploratory. The registry record does not report whether any such approach was planned or used. The primary endpoint is identified as mean BMI at 6 months, but that designation alone does not explain how other outcomes were handled statistically.

Missing-data methods are also not reported in the registry record. The record does not state whether all enrolled participants contributed a primary endpoint measurement, how absent measurements were handled, or whether any sensitivity analyses were performed. In general, missingness can affect estimates if participants with unavailable outcomes differ from those with observed outcomes. The direction and extent of any such effect depend on the data and assumptions; neither is assessable from the information recorded.

The analysis population is not specified. The registry does not describe whether analyses included all enrolled participants, only those who received treatment, or a subset with available measurements. It also does not report protocol deviations or exclusions from the analysis. These omissions matter because different analysis populations can yield different summaries, and the interpretation depends on which participants and observations are included.

Although one analysis is listed, the registry record does not provide its model, covariates, hypothesis, or uncertainty estimates. No multiplicity adjustment, missing-data procedure, or population definition should be assumed in the absence of a report.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: abnormal liver function test (0.0%).

The registry records 24 participants at risk for serious adverse events and 0 serious adverse events. For other adverse events, it records 24 at risk and 0 events. The listed top serious-adverse-event term is “Abnormal Liver Function Test,” with 0.0%. The death count is not reported in the registry record.

These entries describe what the registry records; they do not establish that no adverse events of any kind occurred or that every event was captured. “Serious adverse events” are a specific safety category and should not be treated as synonymous with all symptoms, events, or treatment-related effects. The record does not provide event definitions, collection procedures, exposure duration, severity details, relatedness assessments, or a fuller listing of non-serious events.

A recorded zero is not proof that the underlying risk is zero. In general, when event counts are small or absent, uncertainty about the rate can remain substantial, and interpretation depends on follow-up and ascertainment. No rate estimate or confidence interval is reported in the registry record. The 0.0% figure is reproduced as listed; the record does not explain its denominator or calculation. These safety entries should therefore be read narrowly and alongside the limitations in reporting, rather than as a comprehensive evaluation of safety.

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

The study’s stated question concerns whether febuxostat, by lowering blood uric acid, might affect insulin resistance and other metabolic-syndrome features in adults with gout and hyperuricemia. The registry’s primary endpoint is mean BMI at 6 months. This describes the focus of the registered study, not an observed finding. Numerical BMI results are not reported in the registry record.

Without an endpoint estimate, the direction and magnitude of any BMI result are unknown. Without an uncertainty estimate, its precision cannot be judged. The record does not report a confidence interval, p-value, or detailed analysis method for the primary endpoint. It therefore does not support a conclusion that BMI changed or that an observed change would be attributable to febuxostat.

The design further limits causal interpretation. This is a single-group study with no comparator listed, allocation not applicable, and no masking. In general, observing outcomes in one group cannot rule out alternative explanations for changes over time. The registry does not describe a randomized contrast with another treatment or a control condition, so it cannot establish comparative effectiveness from the design information.

The study summary mentions insulin resistance, blood pressure, insulin levels, waist-area body fat, and cholesterol as features of interest. Their numerical results are not reported in the registry record. BMI should not be taken as a substitute for those separate measures, and the stated rationale should not be mistaken for evidence about their results.

The adverse-event entries record zero serious events and zero other events among 24 at risk in each listed category, with the serious-adverse-event term “Abnormal Liver Function Test” listed at 0.0%. These entries do not establish that all possible harms were absent, and the death count is not reported. The record does not provide the detail needed for a comprehensive safety assessment.

In short, the registry permits a description of the intended population, intervention, design, endpoint, and selected safety entries. It does not provide the outcome estimates needed to judge effects or their precision. The distinction between a study question and a result is essential: the former is stated, while the latter is not numerically reported.

14. Why This Trial Matters Statistically

This study is statistically instructive because its design and its stated research question must be kept separate from evidence of an outcome. The registry describes a phase 4 investigation of febuxostat and metabolic-syndrome features, but the primary endpoint is listed as mean BMI at 6 months and its numerical result is not reported. A clear endpoint definition does not itself tell readers what was observed.

The single-group structure is central to interpretation. Measurements within one group can describe the participants’ outcomes, but without a concurrent comparator the design does not isolate the intervention’s contribution from other influences. This distinction remains important even when the scientific rationale is plausible. Statistical significance, if it were reported, would not by itself resolve limitations created by a non-comparative design.

The record also illustrates why effect estimates and their precision are both needed. A mean without a measure of uncertainty gives limited information about how precisely the underlying quantity is estimated; a measure of spread alone does not provide an intervention effect. Here, neither a numerical primary mean nor an effect estimate or confidence interval is reported. Consequently, readers cannot assess magnitude, precision, or statistical evidence.

Finally, outcome multiplicity, missing data, and the analysis population affect how results should be understood. The registry lists 15 outcome measures and 1 analysis, but does not describe the analysis procedures or how multiple outcomes were handled. It does not report missing-data methods or define the analysis population. These are not minor technical details: they help establish which question was answered, what observations contributed, and how uncertainty was quantified. The absence of those details makes cautious interpretation necessary.

15. 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 immediate limitation is that numerical results for the primary endpoint are not reported in the registry record. Although BMI is identified as the primary outcome and its timeframe is listed as 6 months, the record does not give a mean, standard deviation, effect estimate, or uncertainty interval. It also does not specify whether the outcome is a value at that timepoint or a change from baseline. The endpoint’s observed direction and magnitude therefore cannot be assessed.

The single-group design has no concurrent comparator listed. Allocation is recorded as not applicable and masking as none. This limits causal interpretation because observed outcomes cannot be contrasted with a like-for-like control group in the registry description. The record does not provide information about other care or factors that could influence outcomes during follow-up.

Important methods are not reported: the analysis population, statistical model, covariate adjustment, handling of missing measurements, protocol deviations, and approach to multiple outcomes. The record lists 15 outcome measures and 1 analysis but does not explain their relationship or give detailed results. The death count is not reported in the registry record, and safety-event collection and follow-up details are also absent.

The registry identifies adults older than 21 years with gout and specified hyperuricemia thresholds who require uric-acid-lowering therapy, but it does not provide detailed baseline characteristics. Dose, treatment schedule, adherence, and exact assessment procedures are not reported. These gaps limit assessment of applicability, exposure, and outcome measurement. The recorded enrollment is 24, but that fact alone does not establish how many had complete primary-outcome data or were included in any analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of Hyperuricemia Reversal on Features of the Metabolic Syndrome — NCT01654276.
• Registry record last updated 2023-03-14; status last verified 2023-02.
• Results first posted 2017-01-13.
• 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.

19. Record Summary

The registry record describes a completed phase 4, single-group study of febuxostat in adults with gout and hyperuricemia. The listed enrollment is 24. The study began in 2012-05, reached primary completion in 2015-03, and is sponsored by the University of Texas Southwestern Medical Center.

The primary outcome is mean BMI in kg/m^2 at 6 months. The record lists 15 outcome measures and 1 analysis, but numerical primary-outcome results and detailed statistical methods are not reported in the registry record. No comparator is listed; allocation is not applicable and masking is none. The safety entries record 0 serious adverse events and 0 other adverse events among 24 at risk in each category. The death count is not reported. Overall, the record describes the research question and design but does not provide enough outcome detail to estimate the primary result or its precision.