Effect of Febuxostat Compared to Placebo on Exercise Tolerance in Participants With Chronic Stable Angina: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Febuxostat Compared to Placebo on Exercise Tolerance in Participants With Chronic Stable Angina (NCT01549977), a randomized phase 2 study. The primary outcome is Change From Baseline in Exercise Treadmill Testing (ETT) Duration at Week 12.

2. Clinical Question

3. Trial Design

The registry record describes a Phase 2, randomized, quadruple-masked, placebo-controlled study with a parallel-group model. The stated comparison was febuxostat 80 mg once daily versus placebo, each taken for up to 12 weeks as an addition to stable anti-anginal therapy. Takeda is listed as the sponsor. The condition listed is angina.

The recorded start was 2012-07, and the primary completion date was 2012-11. The study status is terminated. Enrollment is listed as 1. The registry description does not explain the circumstances of termination, the reason enrollment remained at that level, or whether any participant was assigned before the study stopped. Those details are not reported in the registry record.

Randomization is the method of assigning participants to study arms by chance. In general, it is intended to reduce systematic differences between groups at entry, though with very limited enrollment it cannot ensure that groups are comparable. Masking is intended to limit the influence of knowledge about treatment assignment on participant experience, study conduct or outcome assessment. The record labels masking as quadruple, but does not identify the four parties masked or provide further operational details.

The parallel-group model means that the planned comparison was between participants assigned to separate treatment arms, rather than a crossover in which participants receive both interventions. The record lists febuxostat and placebo interventions and corresponding arm descriptions. It does not report a detailed randomization procedure, allocation ratio, site information, protocol deviations, or whether any participant completed the intended treatment duration.

The main design feature for interpreting results is that the primary analysis did not take place. The record explicitly attributes that to only one participant completing the study before termination. Therefore, the design describes an intended comparison, not a completed comparative test of exercise tolerance.

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 chronic stable angina were enrolled in 1 of 2 treatment groups, placebo or febuxostat 80 mg once daily.

Overall Study

Analysis population for the primary outcome, as defined in the registry: This analysis was not performed since only one participant completed the study prior to study termination.

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 Change From Baseline in Exercise Treadmill Testing (ETT) Duration at Week 12, measured over Baseline and Week 12.

The primary endpoint was change from baseline in exercise treadmill testing (ETT) duration at Week 12. It was intended to quantify how a participant’s treadmill exercise time changed between baseline and the Week 12 assessment. The registry record does not specify a unit for the endpoint or provide a numerical definition of the change calculation.

ETT is a structured exercise assessment. According to the registry description, the test used the modified Bruce Protocol. Participants began on a treadmill at 1.7 mph and 0% incline, and exercise intensity, through speed and/or incline, increased at 3 minute intervals. The endpoint therefore focused on exercise duration during a test whose workload progressed over time.

In general, exercise duration can serve as a functional outcome: it records how long a participant exercises under a defined testing procedure. Comparing change from baseline can account for the starting measurement when describing follow-up performance. That general rationale does not establish that a measured change occurred in this study or that any change was caused by treatment.

The registry record states that the primary analysis was not performed because only one participant completed the study before termination. It therefore contains no reported primary endpoint estimate, treatment comparison, confidence interval or significance test. The protocol description explains what the endpoint was intended to measure, but the posted record does not provide an analyzed result for that measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to study arms by chance. In general, this helps prevent treatment assignment from being systematically determined by participant characteristics, and supports a fair comparison when the study has adequate data and is analyzed as planned. It does not guarantee that groups will be balanced, especially when enrollment is very limited. This record describes the study as randomized, but lists enrollment of 1 and says only one participant completed before termination. It does not provide a primary comparative analysis. Randomization therefore describes the intended allocation method, not evidence that the treatment arms can be compared in the posted results.

What do masking and a parallel-group design mean?

In general, masking is used to reduce the risk that knowledge of assigned treatment influences participant reports, care, outcome assessment or analysis. The study is recorded as quadruple-masked. The registry record does not specify which parties were masked or how masking was maintained. A parallel-group design assigns participants to one arm for the planned comparison, rather than having each participant receive both study interventions in sequence. The registry describes febuxostat and placebo arms, but the limited completion means that the design label should not be mistaken for evidence of an estimable treatment contrast.

How should change from baseline be understood?

The primary measure was change in ETT duration from baseline to Week 12. In general, a change score expresses follow-up measurement relative to a participant’s starting value. An analysis might compare change between randomized groups, or use a model that accounts for baseline values. These approaches have different assumptions and may produce different estimates. The registry record does not report which method was prespecified, whether baseline adjustment was planned, or the precise calculation used for the change. It states that the primary analysis was not performed, so there is no posted change estimate to interpret.

What would an estimate and confidence interval convey?

In general, an estimated treatment contrast describes the difference between groups on the outcome scale. A confidence interval communicates uncertainty around that estimate under the analysis assumptions; it is not a guarantee that the true effect lies within the interval. A narrow interval indicates greater precision than a wide one, while an interval spanning values compatible with materially different effects can leave substantial uncertainty. The registry record contains no primary estimate or confidence interval. It is therefore not possible to judge the direction, magnitude or precision of an ETT treatment contrast from the posted primary results.

What would a significance test tell a reader?

In general, a significance test evaluates how compatible observed data are with a specified null hypothesis under a statistical model. A p-value does not measure the probability that a treatment works, and a result that does not cross a chosen threshold does not prove equivalence. Interpretation also depends on the endpoint, analysis population, model assumptions and multiplicity strategy. The statistical plan and primary p-value are not reported in the registry record. Because the primary analysis was not performed, the record offers no test result for the central comparison.

Why do distributional assumptions matter?

In general, methods for continuous outcomes often rely on assumptions about the distribution of measurements or model residuals. Other outcomes, such as counts, can vary more than a simple model expects; this is called over-dispersion and can make standard errors too small if ignored. This is a general statistical point, not a description of an analysis conducted in this study. The primary ETT endpoint is a duration measure, and the registry record does not report an outcome model, diagnostic checks, or evidence that over-dispersion was relevant. No model should be attributed to the trial on the basis of general methodological possibilities.

How do missing data and sample-size illustrations fit?

In general, missing outcome data can affect estimates when participants who contribute follow-up differ from those who do not. Appropriate handling depends on why data are missing, the estimand and the analysis plan. The registry record does not report a missing-data method, a primary analysis population, or whether baseline and follow-up measurements were available for the participant who completed the study. A sample-size planning illustration is a design calculation, not an observed treatment result or observed power. The registry record does not report the trial’s own sample-size justification. Any planning illustration based on an observed effect should be interpreted cautiously when the primary analysis was not performed and no primary effect estimate is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study assesses more than one outcome, time point, subgroup or statistical comparison. In general, conducting multiple tests can increase the chance of at least one apparently notable result arising by chance. Study plans may address this by identifying a primary outcome, specifying a testing sequence, adjusting significance thresholds, or emphasizing estimation rather than isolated tests. The registry record identifies one primary outcome and lists four secondary outcomes, but it does not report a multiplicity strategy, a hierarchy among secondary outcomes, or an adjustment method.

The primary outcome was change from baseline in ETT duration at Week 12. The secondary outcome descriptions include time to onset of angina during ETT, time to onset of at least 1 mm ST-segment depression during ETT, maximum ST-segment depression, and the percentage stopping ETT due to angina. The registry record lists five outcome measures and zero analyses. It does not provide analyzed results for the primary or secondary measures. Therefore, multiplicity cannot be evaluated through the posted inferential results, and no secondary finding should be treated as evidence that resolves the missing primary comparison.

Missing data and analysis populations are similarly under-described. The registry record says only one participant completed the study before termination and that the primary analysis was not performed. It does not state which participants would have been included in an intention-to-treat, per-protocol or other analysis population; those labels should not be assigned to the study without documentation. It also does not report how incomplete ETT assessments, withdrawals or other missing measurements were handled, or whether the participant had both baseline and Week 12 measurements.

In general, missing-data methods rely on assumptions about why observations are unavailable and how missingness relates to measured or unmeasured outcomes. With no reported primary analysis and no description of the relevant participant-level outcome availability, those assumptions cannot be assessed. The registry record does not report interim analyses or a detailed statistical plan. As a result, the intended control of multiplicity, analysis population and missing-data strategy cannot be reconstructed from the posted information.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event counts are listed by arm. In the febuxostat 80 mg group, 1 participant was at risk and 0 were affected. In the placebo group, 0 participants were at risk and 0 were affected. The record does not list serious adverse event terms, and deaths are recorded as null for both groups. A count of 0 affected among 0 at risk is not evidence that no serious adverse events occurred among participants receiving placebo; there were no participants listed at risk in that group.

For other adverse events, the febuxostat 80 mg group has 1 participant at risk and 1 affected. The placebo group has 0 at risk and 0 affected. These registry counts are descriptive. They do not provide a stable comparative estimate of risk, and no rate comparison or statistical test is reported. With no at-risk participants listed for placebo, the two groups do not offer a meaningful exposure-based comparison in these summaries.

In general, adverse-event counts depend on who was exposed, the observation period, event definitions and collection procedures. The registry record does not provide additional details about these elements or event descriptions for the other adverse event. The safety entries should therefore be read as the recorded counts, not as a complete characterization of safety or a basis for comparing treatments.

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

The registry record documents an intended randomized comparison of febuxostat 80 mg once daily and placebo, both added to stable anti-anginal therapy, in participants with chronic stable angina. The primary endpoint was planned as change from baseline in ETT duration at Week 12. The record also describes the exercise test procedure and lists secondary outcomes related to exercise tolerance and ETT findings.

What the record does not provide is an analyzed primary treatment comparison. It explicitly states that the analysis was not performed because only one participant completed the study before termination. There is no reported primary estimate, confidence interval or p-value. The posted results therefore do not quantify whether, or by how much, the treatment arms differed in change in exercise duration.

This absence of an estimate is not evidence that the treatments had identical effects, nor is it evidence that one treatment was superior. Equivalence or non-inferiority would require a suitable prespecified question, margin and analysis; none is reported in the registry record. Likewise, study termination and limited completion do not establish the direction or clinical importance of any potential effect. The primary outcome remains unanswered in the posted analysis.

The adverse-event entries are also limited. The record lists one participant at risk and none affected for serious adverse events in the febuxostat group, with no placebo participants at risk. It lists one participant at risk and one affected for other adverse events in the febuxostat group, again with none at risk in placebo. These counts cannot support a balanced comparative safety assessment.

General statistical interpretation distinguishes an unobserved or unreported estimate from an estimate near zero. Here, the primary analysis was not performed, so there is no estimate whose size or precision can be evaluated. The registry record does not report the reason for termination, detailed analysis methods, missing-data handling or sample-size justification. Conclusions should remain limited to the study design, status, recorded enrollment and the explicit absence of the primary analysis.

13. Why This Trial Matters Statistically

This trial illustrates why a registered design and an analyzed result are different kinds of information. The record describes randomization, masking, two interventions, a primary endpoint and secondary outcomes. Those features explain what investigators intended to compare. They do not, by themselves, establish that a treatment effect was estimated. In this case, the record states that the primary analysis was not performed because only one participant completed the study before termination.

The distinction matters for biostatistical interpretation. An outcome definition can be precise while the result remains unavailable. A stated endpoint and a detailed ETT procedure do not substitute for an observed between-arm estimate, its uncertainty or the analysis assumptions used to produce it. Without those elements, readers cannot assess the size, direction or precision of a comparative effect on exercise duration.

The record also shows why arm-specific denominators matter when reading safety counts. A zero count in an arm with zero participants at risk cannot be interpreted in the same way as zero events among participants who were observed. Denominators and exposure are essential context for event summaries; the placebo entries provide no participant experience on which to base an event-frequency estimate.

Finally, the record highlights limits in reconstructing study methods from registry information. The statistical plan, multiplicity approach, analysis population, missing-data procedures, interim analyses and sample-size justification are not reported in the registry record. These are important for evaluating how an analysis would have been conducted and how results might have been interpreted. Their absence cannot be repaired by assumptions based on usual practice.

The statistical lesson is not a treatment conclusion. It is that registered objectives, methods and results must be distinguished, and that an explicit statement that an analysis was not performed should not be replaced by an imagined null result. This record provides useful design context but no primary estimate with which to answer its stated comparative question.

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 is that the planned primary analysis was not performed. The registry record attributes this to only one participant completing the study before termination. No primary endpoint estimate, between-arm comparison, confidence interval or p-value is reported. Consequently, statistical precision and the magnitude or direction of any treatment contrast cannot be assessed.

Enrollment is listed as 1, and the record gives no further account of participant flow, treatment assignment, exposure duration or assessment completion. It is not reported in the registry record whether the participant had baseline and Week 12 ETT measurements, or whether any incomplete observations were collected. The record also does not describe why the study was terminated.

The statistical plan, analysis population, missing-data approach, multiplicity strategy, interim analyses and sample-size justification are not reported in the registry record. Without these details, the intended analysis cannot be fully reconstructed. The listed secondary outcomes have no reported analyses, so they do not provide an alternative comparative result.

The safety summaries have highly limited denominators: the placebo group has no participants listed at risk. The serious adverse event terms are not listed, and deaths are recorded as null. The other adverse event count in the febuxostat group is descriptive and cannot be compared with an unexposed placebo group.

These limitations concern the information recorded and the lack of an analyzed comparison. They do not establish that an effect was absent, that the study would necessarily have produced a particular result if completed, or why termination occurred. The record supports only a description of the intended design, recorded enrollment and the stated reason the primary analysis was not performed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Febuxostat Compared to Placebo on Exercise Tolerance in Participants With Chronic Stable Angina — NCT01549977.
• Registry record last updated 2013-12-20; status last verified 2013-10.
• Results first posted 2013-12-20.
• 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

The registry record describes a Phase 2, randomized, quadruple-masked, parallel-group, placebo-controlled study sponsored by Takeda. It evaluated febuxostat 80 mg once daily for up to 12 weeks as an addition to stable anti-anginal therapy, compared with placebo. Enrollment is listed as 1, the status is terminated, and the recorded study start and primary completion dates are 2012-07 and 2012-11.

The primary outcome was change from baseline in ETT duration at Week 12, using the modified Bruce Protocol. The registry record states that this analysis was not performed because only one participant completed the study before termination. It lists five outcome measures and zero analyses. No primary treatment-effect estimate is reported. Safety counts are available for the recorded at-risk groups, but the placebo group has no participants listed at risk, preventing a useful comparative reading.