RElugolix VErsus LeUprolide Cardiac Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RElugolix VErsus LeUprolide Cardiac Trial (NCT05320406), a randomized phase 2 study. The primary outcome is Total Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries).

2. Clinical Question

The trial concerns men with localized, non-metastatic prostate cancer receiving definitive radiation therapy, with or without androgen deprivation therapy. The registry lists localized and biochemically recurrent prostate carcinoma and stage I through stage III disease among its conditions. The clinical question is how the addition of leuprolide or relugolix to radiation relates to coronary plaque measurements, compared with radiation alone, over the specified follow-up period.

The trial’s broader stated purpose is to investigate cardiovascular effects associated with androgen deprivation therapy, explore how relugolix may relate to those effects, and identify biomarkers that may help characterize risk. These are research aims, not findings. The posted primary endpoint is a coronary plaque measurement; no analysis results establish whether the arms differ or how precisely any difference has been estimated.

3. Trial Design

NCT05320406 is registered as a phase 2, randomized, single-masked, parallel trial, with enrollment of 94. The record describes three treatment arms: definitive radiation therapy alone, radiation therapy plus leuprolide, and radiation therapy plus relugolix. It identifies Emory University as the sponsor. The listed study status is active, not recruiting.

For the radiation-alone arm, definitive radiation may use IMRT, SBRT, proton therapy, or brachytherapy. The leuprolide arm receives radiation as in the first arm and leuprolide by subcutaneous or intramuscular administration every 3 or 6 months. The relugolix arm receives radiation as in the first arm and relugolix by mouth daily. For both hormone-therapy arms, treatment continues for 6 to 12 months depending on risk, unless disease progression or unacceptable toxicity occurs.

The registry title describes a parallel cohort and randomized trial, while the listed design characteristics identify randomized allocation and a parallel model. Details about a separate cohort, its recruitment, or its relationship to the randomized arms are not reported in the registry record. The record also does not report the allocation ratio, the identity of the masked party, or the method used to generate or conceal assignments.

The listed start date is 2022-06-06, and the primary completion date is 2025-01-30. These are registry dates, not evidence that all follow-up or analyses are complete. The planned primary assessment runs from baseline to 12 months post-treatment initiation. The record gives no protocol-level explanation of the enrollment target, the expected treatment contrasts, or the rationale for the follow-up schedule.

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

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 Total Coronary Plaque Volume in Major Coronary Arteries (i.e. Left Anterior Descending, Left Circumflex, Right Major Coronary Arteries), measured over From baseline to 12 months post-treatment initiation.

The primary endpoint is total coronary plaque volume in major coronary arteries, measured in mm3. The arteries identified include the right coronary artery, left main, left anterior descending, and left circumflex. The registry states that cardiac computed tomography angiography is used and that an artificial intelligence-enabled quantitative coronary plaque analysis service scores plaque volume across coronary segments, which are then summed.

The planned timeframe is from baseline to 12 months post-treatment initiation. This makes the endpoint a measure of change over follow-up rather than a single baseline description. Coronary plaque volume is relevant to the trial’s stated focus on cardiovascular effects of prostate cancer treatment, but the registry record does not report a primary-outcome value or an estimated change for any arm.

The planned summary is the median with a 95% confidence interval. As a general statistical point, the median describes the central point in an ordered set of measurements and is less sensitive than the mean to extreme values. A confidence interval conveys uncertainty in an estimate; it is not a guarantee that the true value lies within its limits. The record does not explain the specific confidence-interval method or how repeated measurements and comparisons among arms will be handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record specifies the primary measure, its summary format, and its timeframe, but reports no primary analysis estimates. It also describes a planning illustration based on an observed effect. The distinction between a planned summary, a result, and a planning calculation is important when reading the statistical information.

What does the planned median represent?

The endpoint is total coronary plaque volume in mm3, summarized using a median and a 95% confidence interval. As a general statistical concept, a median is the middle value after measurements are ordered. It can be useful when a distribution is asymmetric or contains unusually large measurements, because extreme observations have less influence on it than on an arithmetic mean. The registry does not report the distribution of plaque-volume measurements, so it is not possible to assess whether the median is especially suitable for the observed data.

A confidence interval describes uncertainty around an estimate. In general, a narrower interval indicates greater precision than a wider interval, given the method used. It does not describe the range of individual participants’ measurements, and it does not establish a causal interpretation by itself. Although the record names a 95% confidence interval, the particular method used to calculate it is not reported in the registry record. No interval limits are posted for the primary outcome.

How is the endpoint measured?

The registry describes cardiac computed tomography angiography and an artificial intelligence-enabled quantitative coronary plaque analysis service. The right coronary artery, left main, left anterior descending, and left circumflex are scored, and plaque volumes are summed over all segments. The endpoint therefore depends on the imaging and scoring process as well as on the statistical summary. The registry does not report details such as image-reading quality control, reproducibility assessment, handling of technically inadequate scans, or whether readers were masked to treatment assignment.

The primary timeframe is baseline to 12 months post-treatment initiation. For a repeated measurement, an analysis must define how the baseline and follow-up values are combined or contrasted. General options include analyzing follow-up values with adjustment for baseline or analyzing within-participant change; these approaches can have different assumptions and precision. The registry record does not identify which approach was used. It also does not report whether the primary analysis includes all randomized participants, only participants with usable imaging, or another analysis population.

What does the design imply for comparisons?

The record lists randomized allocation, single masking, and a parallel model, with three treatment arms. Randomization is intended, in general, to make assigned groups comparable in expectation, while masking can reduce certain forms of bias. The registry does not identify who was masked or describe the allocation process. Nor does it specify whether the primary analysis compares every pair of arms, focuses on one contrast, or uses another strategy. Without that information and without estimates, there is no defined comparative result to interpret.

As a general statistical point, measurements such as plaque volume may have distributions that depart from the assumptions of simple models. Over-dispersion means that observed variability is greater than a model expects; if relevant and ignored, it can make uncertainty estimates misleading. The registry does not report a distributional assessment, a model, or any method for addressing skewness or over-dispersion. These are possibilities to consider when evaluating a full analysis, not claims about the data in this trial.

How should planning illustrations be read?

The registry describes a planning illustration computed from an observed effect, rather than the trial’s own design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning quantity is participants per arm for 80% power or another stated power level; for time-to-event outcomes, the quantity is the total number of events using the Schoenfeld approach. No particular planning output or effect fraction is reported in the registry record.

As a general concept, a sample-size calculation asks how much information a future study might need under chosen assumptions. It depends on the effect size, variability, significance level, allocation, and analysis method. A calculation using an observed effect is especially dependent on that estimated effect and should not be mistaken for a prospective design rationale. Such calculations are planning illustrations, not observed power, and do not demonstrate that the trial had adequate power for its actual endpoint or comparisons.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and 0 analyses. It identifies total coronary plaque volume as the primary outcome and non-calcified coronary plaque volume in major coronary arteries as a secondary outcome. The record does not provide analysis estimates for these outcomes or describe how the statistical plan treats multiple outcomes, multiple treatment comparisons, or repeated measurements.

Multiplicity arises when several statistical questions are assessed. As a general statistical point, testing many hypotheses can increase the chance of at least one apparently noteworthy result even when no corresponding effect exists. Approaches to multiplicity can include prespecifying a primary contrast, adjusting inference across tests, or presenting estimates with appropriate qualification. Which approach was planned or used is not reported in the registry record. Without that information, a future reader cannot determine from the registry alone how any multiple comparisons should be interpreted.

Missing-data procedures are also not reported. The endpoint requires baseline and follow-up imaging, but the record does not state how missing scans, incomplete measurements, withdrawal, or unusable images are handled. The analysis population is not specified, including whether it is based on randomized assignment, treatment received, or availability of endpoint measurements. The registry also does not report any imputation method, sensitivity analysis, or reasons for missing primary-outcome data.

These omissions matter because the precision and interpretation of an estimate depend on which participants contribute information and how incomplete observations are handled. The absence of these details should not be interpreted as evidence that data are missing or that a particular analysis method was used; those matters 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: sepsis (3.2%).

The registry reports serious adverse-event and other adverse-event counts by arm. In the radiation-alone arm, 0 serious adverse events were reported among 28 participants at risk, and 23 participants were reported in the other adverse-event category among 28 at risk. In the radiation-plus-leuprolide arm, 1 serious adverse event was reported among 31 participants at risk, and 27 participants were reported in the other category among 31 at risk. In the radiation-plus-relugolix arm, 0 serious adverse events were reported among 31 participants at risk, and 30 participants were reported in the other category among 31 at risk.

Deaths are listed as 0 in the radiation-alone arm, 1 in the radiation-plus-leuprolide arm, and 0 in the radiation-plus-relugolix arm. Sepsis is listed among the serious adverse-event terms at 3.2%. The registry record does not provide enough detail to infer the timing, duration, severity distribution, attribution, or overlap among these events. It also does not report comparative statistical analyses of safety outcomes.

These counts are descriptive registry entries. They should not be read as proof that one regimen is safer or more hazardous than another. Differences in counts can reflect the number of participants at risk, event definitions, observation time, and chance; the record does not provide an analysis that accounts for these considerations.

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

The record establishes that a randomized, parallel, phase 2 study is examining coronary plaque volume among men receiving prostate radiation alone or in combination with leuprolide or relugolix. It also specifies a measurement approach using cardiac computed tomography angiography and a planned assessment from baseline to 12 months after treatment initiation. Those details identify the research question and the intended endpoint, but they are not themselves evidence of an outcome.

The registry does not report primary-outcome values, treatment-effect estimates, confidence intervals, or statistical tests. It is therefore not possible to say from the posted results whether plaque volume changed, whether changes differed among arms, or how precisely any such differences were estimated. The lack of posted estimates should not be interpreted as a finding of no effect. Likewise, the study’s stated aims regarding cardiovascular mechanisms and biomarkers do not constitute findings about those mechanisms or biomarkers.

The safety entries give counts in the registry’s serious and other adverse-event categories, along with deaths and a listed serious adverse-event term. These descriptive figures do not establish a comparative safety effect. They also do not explain whether events were related to treatment or whether participants experienced more than one event.

The trial is one study with a stated enrollment of 94 and a particular population, treatment context, endpoint, and follow-up period. The record does not report results that would support extrapolating to other populations, treatment regimens, durations, or cardiovascular outcomes. It also does not report enough methodological detail to judge the analysis of the primary endpoint. The appropriate reading is therefore limited: the registry describes a planned investigation and records some adverse-event counts, while the primary comparative result remains unreported in the registry record.

13. Why This Trial Matters Statistically

This trial brings a cardiovascular measurement into a comparison of prostate cancer treatment strategies. Its primary endpoint focuses on coronary plaque volume assessed by imaging, rather than relying solely on clinical events. Such a measure can be informative for a mechanistic research question, but interpreting it statistically requires clear definitions of the measurement, timing, comparison, and uncertainty. The registry describes some of these elements, including the arteries scored and the planned baseline-to-follow-up timeframe.

The three-arm design is also statistically important. Radiation alone, radiation plus leuprolide, and radiation plus relugolix represent more than one possible contrast. The selected contrast determines the question an estimate answers, and multiple comparisons raise questions about how uncertainty should be handled. The registry record does not report a specific primary contrast or a multiplicity strategy, so the intended inferential framework cannot be reconstructed from the posted information.

Another important issue is the difference between a study’s aims and its reported evidence. The record states aims concerning cardiovascular toxicity, mechanisms, and predictive biomarkers, but it contains no primary analysis estimates. A clear statistical account should distinguish those goals from results and should make the analysis population, missing-data approach, and uncertainty methods available. Those details are not reported in the registry record.

The adverse-event counts add descriptive safety information, but their interpretation is separate from the imaging endpoint and depends on event definitions and follow-up. Taken together, the registry illustrates why a well-defined outcome and a randomized design do not alone answer a clinical research question: readers also need analyzed estimates, uncertainty, and transparent methods. At present, the posted record identifies the question more fully than it reports its statistical answer.

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 the primary endpoint is that no outcome estimates or analyses are reported in the registry record. Although the endpoint, unit, measurement approach, and timeframe are described, the record contains no arm-specific median plaque volumes, confidence-interval limits, or comparative estimates. The direction and precision of any treatment-related change therefore cannot be evaluated.

Important analysis details are not reported. These include the prespecified treatment contrast, the statistical model or estimation procedure, handling of repeated measurements, analysis population, and approach to missing or unusable imaging. The registry also does not describe the multiplicity strategy, the method used for confidence intervals, or any sensitivity analyses. These gaps restrict assessment of how robust a future estimate would be and what population it represents.

The design details are incomplete for evaluating potential bias. The record states single masking but does not identify who was masked. It does not report the randomization sequence or allocation concealment. The title refers to a parallel cohort and randomized trial, but the cohort’s design and its connection with the randomized component are not described in the record. The allocation ratio is also not reported.

The primary endpoint is an imaging-based surrogate measure, and the record does not provide results linking its change to clinical cardiovascular events. The available safety counts are descriptive and lack comparative analyses and contextual information about event ascertainment. Finally, the listed enrollment and registry dates do not supply a sample-size justification or establish completion of endpoint follow-up. These limitations mean that the registry information alone supports a description of the study plan and posted safety counts, not a conclusion about comparative efficacy or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: RElugolix VErsus LeUprolide Cardiac Trial — NCT05320406.
• Registry record last updated 2026-02-12; status last verified 2026-01.
• Results first posted 2025-09-22.
• 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

NCT05320406 is a phase 2, randomized, single-masked, parallel trial sponsored by Emory University, with enrollment of 94 and status active, not recruiting. The arms are radiation therapy alone, radiation therapy plus leuprolide, and radiation therapy plus relugolix. The listed primary endpoint is total coronary plaque volume in major coronary arteries, measured by cardiac computed tomography angiography and summarized as a median with a 95% confidence interval from baseline to 12 months post-treatment initiation.

The registry lists 7 outcome measures and 0 analyses. It reports adverse-event counts by arm but no primary-outcome estimates or comparative analyses. Details on the primary statistical model, missing data, analysis populations, and multiplicity are not reported in the registry record.