Isoflavones and the Coronary Circulation in Men and Women With Coronary Artery Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Isoflavones and the Coronary Circulation in Men and Women With Coronary Artery Disease (NCT00287690), a randomized phase 2, phase 3 study. The primary outcome is Coronary Artery Diameter.

2. Clinical Question

This is a question about a measured coronary-artery response in a specific trial population and time window. It is not, by itself, a question about symptoms, later cardiovascular events, or long-term health. Those outcomes are not identified as the primary endpoint in the registry record. The record also names serum genistein concentrations as a secondary outcome, but the posted results described for the primary comparison concern artery diameter.

The trial’s stated aim was to investigate the effect of genistein administration on coronary arteries in humans. Its results therefore need to be read as an estimate of the difference between the randomized groups on this particular measurement. The group summaries do not establish what would happen in other populations, with other doses or durations, or on outcomes not reported in the registry record.

3. Trial Design

The registry identifies the study as randomized, quadruple-masked, and parallel-group, with Phase 2 and Phase 3 listed. A parallel-group design assigns participants to one study group and compares outcomes between groups rather than having each participant receive both study drinks. Random allocation is intended to make assignment less dependent on participant or investigator choice; masking is intended to limit knowledge of assignment during trial conduct or assessment. The registry does not specify which four roles were masked or describe how randomization and masking were implemented.

The study is listed as completed, with Imperial College London as sponsor. Registry dates give a start of 1999-10 and primary completion of 2003-08-18. Enrollment is recorded as 71. This is a registry enrollment figure, not a claim that every enrolled participant contributed data to the primary endpoint. The posted primary summaries report 13 participants in the genistein group and 12 in the placebo group. The record does not explain the relationship between those outcome counts and overall enrollment.

The genistein group received Supro once daily for 3 days; the placebo group received a drink described as identical but without genistein, also once daily for 3 days. The primary endpoint timeframe is Day 3-4 after the drinks started. The record describes coronary angiograms acquired digitally and analysed using quantitative coronary angiography, with measurements of mean luminal diameter. It states that the reported primary data concern mean coronary artery diameter response following acetylcholine infusion.

Important operational details are not reported in the registry record. These include the randomization sequence and concealment procedures, the exact masking arrangements, the treatment of protocol deviations, and the original statistical analysis plan. The listed phases and design labels describe registry classifications; they do not supply those missing procedural details.

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 Coronary Artery Diameter, measured over Day 3-4 after Supro/placebo started..

The primary endpoint is coronary artery diameter, a continuous measurement reported in millimetres. The registry describes measurements of basal luminal diameter along the coronary artery and a measurement near the tip of the Doppler wire. It specifies that the posted primary results are mean coronary artery diameter response following infusion of acetylcholine. The timeframe is Day 3-4 after Supro or placebo started.

A continuous diameter measure preserves the magnitude of the measured response rather than reducing it to a yes-or-no event. Comparing group means can describe whether the average recorded diameter response differed between randomized groups. The standard deviation gives information about how dispersed individual measurements were around each group mean; it is not a confidence interval for the group mean or for the between-group difference.

Coronary angiography and quantitative coronary angiography are identified as the measurement and analysis approaches in the registry description. In general, a measured artery diameter can serve as a physiological endpoint when a study is examining coronary-artery responses. That interpretation is limited to the specific measurement, procedure, and timeframe used. The endpoint is not itself a measure of symptoms, clinical events, or long-term outcomes, and the registry record does not report those as the primary outcome.

The registry lists serum genistein concentrations as a secondary outcome. It does not provide a result for that outcome in the registry record described for this analysis. The primary interpretation therefore rests on the posted diameter summaries and their comparison, not on an assumed relationship between measured genistein concentrations and artery response.

7. Results Posted in the Registry

• Genistein: mean 3.10 versus 2.70 on control; difference 0.40 (95% CI 0.09 to 0.71), standardized effect d = 1.00; z-test p = 0.012.

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is this? Coronary artery diameter is continuous: it can take a range of measured values rather than being classified only as an event or non-event. The registry reports a mean and standard deviation for each group. The mean describes the group’s average measurement. The standard deviation describes variability among measurements within that group. It does not measure uncertainty in the estimated difference by itself, and it should not be read as a margin of error around the mean.

What does the group comparison estimate? The posted comparison is the genistein mean minus the placebo mean, reported as a mean difference of 0.4 mm. This is an unadjusted comparison based on the posted summary statistics. An unadjusted estimate compares the groups without accounting for other covariates in a regression model or other adjustment procedure. The registry record does not report an adjusted estimate, covariate list, or analysis model. The simple difference is interpretable on the original measurement scale, but it does not account for any potential influence of baseline characteristics or other variables.

How should the p-value be read? The reported unadjusted p-value is 0.012. In general, a p-value is calculated under a null hypothesis and statistical model; it measures how unusual the observed data, or data more extreme, would be if that model were correct. It does not express the probability that treatment has no effect, and it does not measure the probability that the observed difference arose “by chance.” Its interpretation relies on assumptions about the data and analysis. The registry record does not specify the test used for the posted comparison, so a more detailed account of its calculation is not reported in the registry record.

What do randomization and masking contribute? Random allocation can help balance measured and unmeasured participant characteristics across groups in expectation, while masking can reduce bias that might arise if knowledge of assignment affects care, measurement, or reporting. These are general design principles. The registry labels this study randomized and quadruple-masked, but does not describe sequence generation, allocation concealment, which roles were masked, or whether masking was maintained. The labels alone do not establish the success of each procedure.

Why can dispersion matter? Continuous measurements often differ from person to person. The posted standard deviation of 0.4 mm in both groups conveys variation in the observed diameter measurements. Greater variability generally makes a group difference harder to estimate precisely for a given amount of data. If variability is not captured adequately by a model, standard errors and confidence intervals can be misleading. Over-dispersion is a general concern when data vary more than a statistical model assumes; the registry record does not report an over-dispersion assessment, and this endpoint is summarized as a mean with standard deviation.

What does a confidence interval add? A confidence interval presents an estimate together with a range reflecting sampling uncertainty under a method’s assumptions. The interval reported for the mean difference lies above zero. That is consistent with the direction of the estimated difference, but the interval does not establish the probability of a particular effect size. Its interpretation depends on the calculation method and assumptions. The registry record does not identify a sponsor analysis or document a confidence-interval procedure; the comparison is a simple unadjusted recalculation from posted summary statistics.

Why distinguish the reported comparison from a trial analysis plan? A registry outcome summary and a prespecified statistical analysis plan are not interchangeable. A plan can specify the analysis population, handling of missing measurements, covariate adjustment, outcome transformations, and multiplicity procedures before results are known. Those details are not reported in the registry record. Consequently, the displayed comparison can be described as an unadjusted summary-based estimate, but it cannot be assumed to reproduce a planned primary analysis.

What can be inferred from the endpoint counts? The primary group summaries list 13 genistein participants and 12 placebo participants. These counts identify the participants included in the reported outcome summaries, but the record does not explain why they differ from the enrollment figure of 71. They should not be treated as a complete participant-flow account. The registry record does not report the number randomized to each group, exclusions, missing measurements, or the analysis population definition.

How should the design labels be kept in perspective? Randomized, quadruple-masked, parallel-group design labels are relevant context, not a substitute for methods detail. In general, randomization supports causal comparison when implemented appropriately and when analysis respects assignment, while masking can limit assessment and performance biases. Attrition, deviations from assigned treatment, measurement practices, and selective outcome reporting can still affect conclusions. The registry record does not report enough detail to evaluate those issues fully.

What is not established by statistical significance? A p-value below a conventional threshold does not by itself establish clinical importance, reproducibility, or generalizability. The estimate’s magnitude, precision, measurement context, analysis choices, and study population all matter. Here, the result concerns a short-term mean diameter response after acetylcholine infusion. The registry record does not report a threshold for a clinically important difference, so the clinical meaning of the measured difference is not established by the p-value.

10. Confidence Intervals and Precision

The mean difference is reported as 0.4 mm, with a confidence interval that lies above zero. This interval communicates uncertainty around the estimated difference, rather than the range of individual participant measurements. The standard deviation of 0.4 mm in each group describes variation in participant measurements and serves a different purpose. Keeping these quantities separate is essential: a group can have variable individual measurements while the estimated group contrast has its own sampling uncertainty.

The interval’s position indicates that the comparison’s estimated direction is positive for genistein relative to placebo. It does not show that every participant had a larger diameter response, nor does it identify the true difference with certainty. In general, a confidence interval is produced by a method with assumptions; repeated use of that method under its assumptions would have a stated coverage property. It is not a probability statement about the fixed true value after observing one interval.

The primary outcome summaries include 13 participants in the genistein group and 12 in the placebo group. With limited endpoint counts, estimates can be sensitive to individual observations, and uncertainty should be considered alongside the point estimate. The registry record does not provide participant-level values, a sensitivity analysis, or an account of missing measurements, so the stability of the estimate cannot be assessed from the summary alone.

The p-value is 0.012, but it should not be used as a substitute for the confidence interval or as a measure of precision. Precision concerns how tightly the effect is estimated; statistical evidence against a null model and the practical importance of an effect are distinct questions. The registry record does not report a clinically meaningful threshold for the diameter measure.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total event counts. They are illustrations based on the observed mean difference, not the trial’s original design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect.

For planning at 100% of the observed effect, the figures are 16 participants per arm for 80% power and 22 participants per arm for 90% power. At 75% of the observed effect, they are 28 participants per arm for 80% power and 38 participants per arm for 90% power. At 50% of the observed effect, they are 63 participants per arm for 80% power and 85 participants per arm for 90% power.

In plain terms, power is the chance that a study would meet its chosen statistical criterion if the assumed effect and model were correct. The 80% column describes a planning target with that power level; the 90% column uses a higher target and therefore calls for more participants for each stated effect. Smaller effects need more participants to detect with the same planned power, as reflected in the increasing figures for lower fractions of the observed effect.

These values are planning illustrations, not observed power. They are not evidence that the completed trial had those sample sizes or that it was designed using these assumptions. The original trial sample-size justification, design effect, and power target are not reported in the registry record. The illustrations depend on the observed effect and the stated assumptions, so they should not be interpreted as a reconstruction of the investigators’ original plan.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.400; pooled standard deviation σ = 0.400.
2. n = 2 × (1.96 + 0.842)² × 0.400² / 0.400² = 15.7, rounded up to 16 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.4                      # observed difference in means
sigma <- 0.4                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(287690)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 16 (80% power), 22 (90% power)
 75% of observed effect: n per arm = 28 (80% power), 38 (90% power)
 50% of observed effect: n per arm = 63 (80% power), 85 (90% power)
power.t.test: 16.7 
Simulated power at n = 16 per arm: 0.783 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record identifies coronary artery diameter as the primary outcome and serum genistein concentrations as a secondary outcome. It also records three outcome measures, but the other measure details are not reported in the registry record. The record lists no posted analyses. It does not describe whether multiple endpoints, time points, or comparisons were tested as part of a broader analysis.

Multiplicity arises when several statistical hypotheses are examined. In general, making many comparisons can increase the chance of at least one apparently notable result if each is evaluated without an appropriate strategy. A prespecified hierarchy, adjustment method, or clear distinction between primary and exploratory analyses can help readers interpret multiple results. The registry record does not report a multiplicity adjustment or a plan for handling multiple tests. It would therefore be inappropriate to assume that the reported p-value was adjusted, or to claim that it was not, beyond the fact that the comparison is labelled unadjusted.

Missing-data procedures are also not reported in the registry record. The record gives endpoint counts for the two groups but does not say whether participants lacked measurements, why any measurements were unavailable, or how missing observations were handled. It does not report imputation, complete-case rules, or sensitivity analyses. The difference between overall enrollment and the endpoint counts cannot be explained from the registry information alone.

The analysis population is not defined. The record does not state whether participants were analysed according to randomized assignment, treatment received, or another rule. It also does not report protocol deviations or withdrawals. These distinctions matter because excluding participants or using a population other than the randomized groups can affect the comparability that randomization is intended to support.

Accordingly, the posted unadjusted comparison is interpretable as a summary-based contrast, but the registry record does not establish how it relates to a prespecified confirmatory analysis. The original statistical plan, multiplicity strategy, missing-data approach, and analysis-population definition are not reported in the registry record.

14. 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.

The serious adverse event figures list 0 serious adverse events in the genistein group, with 13 participants at risk, and 0 in the placebo group, with 12 participants at risk. Deaths are listed as 0 in both groups. The registry also records 0 other adverse events in each group. These are the counts reported in the registry record; they should not be interpreted as evidence that no adverse effects occurred outside the categories or reporting period captured there.

A zero count means that no event in that category was recorded for the listed group in the posted safety figures. It does not prove that the underlying event risk is zero. When event counts are absent or very small, estimates of event frequency are imprecise, and differences between groups are difficult to assess. The record does not report detailed definitions, event collection procedures, observation duration for safety, severity grading, or relatedness assessments.

The short treatment schedule is described as once daily for 3 days, but the registry safety figures do not provide enough detail to establish the full safety follow-up window. The listed participants at risk are not necessarily the same as the full enrolled population, and the registry does not explain the safety analysis population. These figures are a limited summary of recorded adverse events, not a comprehensive safety evaluation.

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

The result indicates that, among participants represented in the posted primary summaries, the mean coronary artery diameter response following acetylcholine infusion was 3.1 mm in the genistein group and 2.7 mm in the placebo group. The unadjusted mean difference is 0.4 mm, and the reported p-value is 0.012. The confidence interval lies above zero, while still expressing uncertainty around the estimated difference.

That finding is confined to a specific measurement, in a specific population, over a short timeframe after treatment began. It does not establish an effect on symptoms, cardiovascular events, survival, or long-term health. Those outcomes are not reported as the primary endpoint in the registry record. Nor does a difference in an artery-diameter measurement by itself establish that a treatment is clinically beneficial or harmful.

The comparison is based on group summaries and is unadjusted. The registry record does not report the original statistical analysis plan, the analysis population, missing-data procedures, or a multiplicity strategy. Those omissions limit assessment of how the posted result relates to the trial’s intended analysis and how robust it is to alternative analysis decisions. The record also does not explain why endpoint counts are smaller than the overall enrollment figure.

Randomization and quadruple masking are listed as design features, but implementation details are not reported in the registry record. These labels are relevant, while not sufficient on their own to evaluate possible bias. Further, the posted endpoint counts are limited, and no individual-level data or sensitivity analyses are reported.

The careful conclusion is descriptive: the posted results show a larger mean diameter response in the genistein group than in the placebo group for the reported endpoint and timeframe, with an unadjusted estimate whose interval lies above zero. The results do not determine the clinical importance of the difference, its durability, or its applicability to populations beyond those represented in the trial.

16. Why This Trial Matters Statistically

This trial illustrates the distinction between a physiological endpoint and a clinical outcome. Coronary artery diameter after acetylcholine infusion can be summarized as a continuous measurement, allowing a mean difference to retain the measurement’s scale. Yet a difference in that measure does not automatically translate into a difference in how participants feel or in later health events. Statistical interpretation must stay aligned with what was actually measured.

It also demonstrates why effect estimates, variability, and uncertainty should be read together. The group means and their standard deviations describe the observed summaries; the mean difference describes the contrast; and the confidence interval communicates uncertainty around that contrast. The p-value contributes a separate test-based summary. None of these quantities alone establishes clinical importance or generalizability.

The registry record’s reporting gaps matter for interpretation. Randomization and masking are identified, but their procedures are not detailed. The endpoint counts are substantially more limited than the recorded enrollment, without an explanation in the registry record. The analysis population, missing-data approach, and multiplicity plan are also not reported. These omissions do not erase the posted result, but they restrict how fully readers can evaluate potential bias and robustness.

Finally, planning calculations based on an observed effect are not the same as the trial’s original sample-size rationale. Reading such calculations as design history or observed power would confuse a retrospective illustration with a prespecified plan. This distinction is central to responsible interpretation of trial statistics.

17. 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.

Several limitations specific to this trial follow directly from the registry record. The primary comparison includes 13 participants in the genistein group and 12 in the placebo group, while overall enrollment is recorded as 71. The record does not explain this difference, identify the number randomized to each group, or provide participant flow. As a result, the endpoint summaries cannot be assumed to include all enrolled participants, and the reasons for the reported outcome counts are not known.

The registry labels the study randomized and quadruple-masked, but does not report the randomization method, allocation concealment, or which roles were masked. It also does not describe adherence, treatment discontinuation, protocol deviations, or measurement quality control. These gaps prevent detailed assessment of how design features operated in practice.

The primary result is an unadjusted recalculation from posted group summaries. The registry record does not report the original analysis plan, an adjusted estimate, the analysis population, missing-data handling, or sensitivity analyses. It also does not report a multiplicity strategy. The confidence interval and p-value therefore should be read in the context of a limited account of the analysis methods.

The endpoint is a short-term coronary artery diameter response following acetylcholine infusion, assessed on Day 3-4 after treatment started. The record does not report long-term outcomes or a clinically meaningful threshold for this measure. Safety reporting is similarly limited to the posted event counts, without detailed definitions or follow-up information. These constraints restrict conclusions about durability, clinical relevance, and safety beyond the recorded summaries.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Isoflavones and the Coronary Circulation in Men and Women With Coronary Artery Disease — NCT00287690.
• Registry record last updated 2019-08-05; status last verified 2006-02.
• Results first posted 2019-08-05.
• 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.

21. Record Summary

NCT00287690 is a completed randomized, quadruple-masked, parallel-group study sponsored by Imperial College London. The registry lists Phase 2 and Phase 3 and enrollment of 71. The study compared a Supro drink containing genistein, taken once daily for 3 days, with an otherwise identical placebo drink containing no genistein.

The primary outcome was coronary artery diameter in millimetres, measured on Day 3-4 after treatment started and reported as a response following acetylcholine infusion. The posted group means were 3.1 mm for genistein and 2.7 mm for placebo, with standard deviations of 0.4 mm in both groups. The unadjusted mean difference was 0.4 mm, with p = 0.012.

The registry names serum genistein concentrations as a secondary outcome. It reports no serious adverse events or deaths in the posted group figures. Details of the original statistical plan, analysis population, missing-data handling, and multiplicity procedures are not reported in the registry record.