Inflammation and Coronary Endothelial Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Inflammation and Coronary Endothelial Function (NCT02366091), a randomized phase 2 study. The primary outcome is Percent Change in Coronary Cross Sectional Area (CSA) From Rest to That During Isometric Handgrip Exercise (IHE).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, triple-masked, factorial phase 2 trial. It lists an enrollment of 111 and a completed status. The study start is recorded as 2015-01, and primary completion as 2020-08-01. The study was sponsored by Johns Hopkins University. The record does not specify which groups of people were masked, how randomization was generated or implemented, or how the factorial structure was handled in the analysis.

Four groups are listed: methotrexate, colchicine, methotrexate with colchicine, and placebo. Methotrexate was taken by mouth weekly at 15 mg; colchicine was taken by mouth daily at 0.6 mg; and folate was listed at 1 mg by mouth daily in each arm description. Each single-drug group also received a placebo matching the other study drug, while the placebo group received placebos for both drugs. This arrangement permits comparisons of each listed active regimen with placebo. It does not, by itself, establish that interaction effects or factorial main effects were analyzed or reported.

The primary endpoint was assessed at 8 weeks. Posted primary outcome summaries include 21 participants in the methotrexate group, 16 in the colchicine group, 21 in the combination group, and 22 in the placebo group. These are outcome-specific counts, not a substitute for the enrollment figure. Reasons for the different analysis counts, and details of participant flow or the analysis population, are not reported in the registry record.

The registry lists additional outcomes at 8 and 24 weeks, including coronary cross-sectional area and coronary blood flow measured during handgrip exercise, serum high-sensitivity C-reactive protein, interleukin-6, and brachial flow-mediated dilation. A detailed protocol, original statistical analysis plan, original sample-size justification, and specific masking procedures are not reported in the registry record.

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: 17 enrolled participants were excluded from the study prior to randomization as follows: 9 did not qualify by screening MRI; 3 did not qualify by lab work; 3 declined to proceed after qualifying by MRI; 2 were not randomized as enrollment target was met.

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 Percent Change in Coronary Cross Sectional Area (CSA) From Rest to That During Isometric Handgrip Exercise (IHE), measured over At 8 weeks.

The primary endpoint is the percent change in coronary cross-sectional area from its resting measurement to the measurement during isometric handgrip exercise, assessed by MRI at 8 weeks. In the registry description, this measure represents coronary segment endothelial function. The comparison is based on the group mean, and the posted spread is a standard error rather than a standard deviation.

In general, a measure of vessel response to a stress challenge can characterize how the coronary segment changes from rest when demand is increased. Expressing the change relative to the resting measurement places the endpoint on a percent-change scale. The endpoint is used to assess a physiological response, rather than a clinical event such as hospitalization or death. The registry record does not describe a minimum clinically important difference or explain how a particular change in this MRI measure should be interpreted for an individual patient.

The primary assessment occurred at 8 weeks. The registry also lists coronary cross-sectional area at 24 weeks as a secondary outcome, which allows a later measurement of the same general response. Results at the later assessment should be distinguished from the designated primary assessment: they do not replace the 8-week primary comparison. The record does not report a protocol rationale for selecting the endpoint or assessment time.

7. Results Posted in the Registry

• Methotrexate: mean -1.70 versus 2.04 on control; difference -3.74 (95% CI -10.62 to 3.14), standardized effect d = -0.33; z-test p = 0.287.
• Colchicine: mean 2.71 versus 2.04 on control; difference 0.67 (95% CI -7.69 to 9.03), standardized effect d = 0.06; z-test p = 0.875.
• Methotrexate & Colchicine: mean -0.39 versus 2.04 on control; difference -2.43 (95% CI -8.37 to 3.51), standardized effect d = -0.25; z-test p = 0.422.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percent Change in Coronary Cross Sectional Area (CSA) From Rest to That During Isometric Handgrip Exercise (IHE)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Methotrexate: mean 1.94 versus 9.26 on control; difference -7.32 (95% CI -16.03 to 1.39), standardized effect d = -0.54; z-test p = 0.100.
  • Colchicine: mean -5.39 versus 9.26 on control; difference -14.65 (95% CI -24.20 to -5.10), standardized effect d = -1.11; z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Methotrexate and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Colchicine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percent Change in Coronary Blood Flow (CBF), Measured by MRI as the Change From Rest to IHE Stress

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Methotrexate: mean 10.23 versus 13.81 on control; difference -3.58 (95% CI -16.58 to 9.42), standardized effect d = -0.16; z-test p = 0.589.
  • Colchicine: mean 14.06 versus 13.81 on control; difference 0.25 (95% CI -12.57 to 13.07), standardized effect d = 0.01; z-test p = 0.970.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Methotrexate and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Colchicine and the control. The interval gives the range of effects that remain compatible with the data.

Serum High-sensitivity C Reactive Protein (Hs-CRP)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Methotrexate: mean 2.40 versus 1.65 on control; difference 0.75 (95% CI -0.56 to 2.06), standardized effect d = 0.35; z-test p = 0.260.
  • Colchicine: mean 3.10 versus 1.65 on control; difference 1.45 (95% CI -1.93 to 4.83), standardized effect d = 0.32; z-test p = 0.400.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Methotrexate and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Colchicine and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists several secondary outcome domains alongside the primary MRI measure: coronary cross-sectional area at a later assessment, coronary blood flow during handgrip exercise, blood measures of inflammation, and brachial flow-mediated dilation. The posted secondary summaries cover only some of these listed outcomes. Results for interleukin-6 and brachial flow-mediated dilation are not reported in the registry record. The presence of an outcome in the registry list should not be mistaken for a posted result.

Across the reported secondary summaries, the pattern is not uniformly aligned with the primary comparisons. Some group estimates point in different directions, and their uncertainty varies. One recalculated secondary comparison has an interval that does not include zero, while many of the other reported comparisons have intervals that include zero. These secondary findings can add context about other physiological and inflammatory measures, but they do not resolve the uncertainty in the primary endpoint or establish a consistent pattern across outcomes.

The later coronary cross-sectional-area measurement is related to the primary endpoint because it assesses the same general MRI response at a different time. Coronary blood flow, inflammatory markers, and brachial flow-mediated dilation measure different aspects of physiology. Agreement across measures could be informative, but disagreement is not surprising when endpoints differ in what they measure and how precisely they are estimated. The registry record does not report a formal analysis linking changes across these outcomes.

Secondary outcomes usually carry less confirmatory weight when many outcomes or comparisons are considered, especially if no multiplicity plan is reported. When many tests are examined, some apparently notable findings can occur by chance. The registry record does not report an adjustment for multiple comparisons, a hierarchy of secondary hypotheses, or a complete analysis plan. Secondary p-values and intervals should therefore be treated as exploratory descriptions rather than independent confirmation of a treatment effect.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percent Change in Coronary Cross Sectional Area (CSA) From Rest to That During Isometric Handgrip Exercise (IHE)
• Percent Change in Coronary Blood Flow (CBF), Measured by MRI as the Change From Rest to IHE Stress
• Serum High-sensitivity C Reactive Protein (Hs-CRP)
• Serum Interleukin-6 (IL-6)
• Brachial Flow Mediated Dilation (FMD)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a mean percent change in a measurement of coronary cross-sectional area. The registry reports one mean and one standard error for each group. A mean describes the group’s average observed outcome. The standard error describes the uncertainty around that estimated mean; it is not a description of how widely individual participants’ values vary. In general, a standard deviation is used to describe variation among observations, while a standard error reflects the precision of an estimated mean.

What does the mean difference represent?

Each posted primary comparison sets a treatment-group mean against the placebo mean. The recalculated mean difference is treatment minus placebo, so a negative estimate means the treatment-group mean was lower on this endpoint, while a positive estimate means it was higher. This is a simple, unadjusted comparison derived from the posted summary statistics. It does not account for any covariates, stratification, or other features of a trial analysis that are not reported in the registry record. The record does not post a sponsor-reported analysis for these comparisons.

How should the intervals be read?

A confidence interval gives a range of values compatible with the observed data under the method used to calculate it. A narrow interval indicates greater precision; a wide interval indicates less. For the primary comparisons, every reported interval includes zero. Zero represents no mean difference between the compared groups. The intervals also extend to values in both directions, so the estimates do not pin down the direction or size of a difference with precision. The confidence level and exact interval procedure are not reported in the registry record, so they should not be inferred from the displayed limits.

What does an unadjusted p-value convey?

A p-value is a measure of how compatible the observed data are with a specified null model, given the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The posted primary p-values are labelled unadjusted. The registry record does not report whether the primary analysis used a prespecified significance threshold, whether covariates were included, or whether any multiplicity procedure was planned. The p-values should therefore be read as descriptive inferential summaries, not as a complete account of the analysis plan.

What does factorial mean in this setting?

In general, a factorial design studies multiple treatment factors within one trial. This trial lists methotrexate and colchicine in single-drug and combined groups, alongside a placebo group. A factorial analysis may estimate effects of each factor and examine whether the effect of one factor depends on the other. The presence of a factorial design does not establish that those analyses were performed. No factorial main-effect or interaction results are reported in the registry record. The posted group-by-group comparisons with placebo answer narrower questions about the listed regimens.

Why does over-dispersion matter?

Over-dispersion is a concern when observed variability is greater than a statistical model expects. In general, ignoring it can make uncertainty appear smaller than it is. The primary endpoint is continuous, and the registry reports means and standard errors; it does not report a model-based dispersion assessment. Over-dispersion methods used for count outcomes should not be assumed to apply to these mean comparisons. More broadly, the appropriateness of a model depends on the outcome distribution and the analysis method, neither of which is fully described in the registry record.

The calculations labelled recalculated are simple unadjusted comparisons from the posted summaries. They are useful for interpreting the displayed means, but they do not recover participant-level data or a potentially adjusted sponsor analysis. No discrepancy is flagged for these calculations. The registry record does not report missing-data methods, analysis-population definitions, covariate adjustment, or sensitivity analyses. Those omissions limit how fully the posted statistics can be reconstructed or evaluated.

11. Confidence Intervals and Precision

Precision is a central issue for the primary result. The recalculated mean difference for methotrexate versus placebo is -3.74, with a reported interval from -10.62 to 3.141. For colchicine versus placebo, the estimate is 0.67, with an interval from -7.689 to 9.029. For the combination versus placebo, the estimate is -2.43, with an interval from -8.367 to 3.507. Each interval spans zero and includes values on both sides of it.

These ranges indicate that the posted data do not tightly determine the size or direction of the mean differences. For example, the methotrexate and combination estimates are negative, while the colchicine estimate is positive, but the intervals do not confine the plausible difference to that observed direction. The reported limits are especially important because the point estimate alone can give a misleading impression of certainty. A point estimate is one value calculated from the observed data; an interval expresses uncertainty around that estimate.

The registry record does not state the confidence level or the exact method used for the reported intervals. The standard errors are also appreciable relative to the group means, and the endpoint-specific group counts range from 16 to 22 for the primary comparison. These registry entries help describe the precision of the posted summaries, but they do not explain why the counts differ. Reasons for missing observations, the trial’s original precision targets, and its own sample-size assumptions are not reported in the registry record.

Interval inclusion of zero does not establish that the groups are identical. Rather, it means the observed data and reported uncertainty do not isolate a nonzero difference. Conversely, the point estimates alone should not be treated as proof of an effect. Interpretation should consider the interval, the unadjusted nature of the recalculations, and the absence of a reported sponsor analysis plan.

12. 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 illustrations based on the observed effect in each comparison, not the trial’s original design calculation. For these continuous outcomes, the displayed figures are participants per arm, not total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario uses the stated fraction of the observed effect as the effect to detect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column represents the number of participants per arm that a hypothetical study would need, under those planning assumptions, to have an 80% chance of detecting the selected effect if that effect were real. The 90% power column gives the corresponding number for a 90% chance. These are planning concepts, not probabilities that the present trial’s result is correct. The figures are not observed power.

Rows based on 100% of the observed effect use the full point estimate from the posted comparison. Rows based on 75% or 50% use smaller effects than that observed estimate. Smaller effects are harder to distinguish from random variation under the same assumptions, so they require more participants per arm to reach the same target power. The displayed values therefore increase as the effect to detect becomes smaller.

The illustrations should not be read as evidence that the trial was designed to enroll any particular number. They also do not incorporate details that might be part of a full trial design, such as anticipated attrition, covariate adjustment, or the handling of multiple outcomes; those details are not reported in the registry record. The curve can be read as a visual representation of the same planning relationship, not as a new estimate of the trial’s results.

13. 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 = -3.740; pooled standard deviation σ = 11.426.
2. n = 2 × (1.96 + 0.842)² × 11.426² / -3.740² = 146.5, rounded up to 147 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 <- -3.74                      # observed difference in means
sigma <- 11.4263335134668                     # 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(2366091)
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 = 147 (80% power), 197 (90% power)
 75% of observed effect: n per arm = 261 (80% power), 349 (90% power)
 50% of observed effect: n per arm = 587 (80% power), 785 (90% power)
power.t.test: 147.5 
Simulated power at n = 147 per arm: 0.802 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and multiple secondary outcomes, and the posted comparisons include more than one active regimen against placebo. Considering several outcomes and comparisons creates a multiplicity issue: the more statistical tests considered, the greater the chance that at least one result appears noteworthy by chance. In general, a prespecified testing hierarchy or adjustment procedure can address this concern. Neither is reported in the registry record.

The posted primary p-values are unadjusted. The record does not state whether the trial’s original analysis plan included an adjustment, whether the 8-week primary endpoint was the sole confirmatory test, or whether secondary outcomes were intended to be exploratory. No reported analyses are listed for the secondary summaries. The record also does not describe how the factorial design was incorporated into inferential testing, including whether interaction effects were assessed. As a result, the posted comparisons should not be interpreted as a complete account of the planned statistical analysis.

Participant counts differ across outcomes and groups. For the primary endpoint, the registry reports group counts of 21, 16, 21, and 22; other posted outcomes have different counts. The registry record does not explain the differences, describe missing observations, or specify whether analyses used an intention-to-treat, per-protocol, or other population. It does not report imputation, complete-case rules, sensitivity analyses, or the handling of participants with unavailable measurements.

These omissions matter because missingness can affect both precision and the interpretation of group comparisons. In general, methods that assume missing observations are unrelated to outcomes can perform differently from methods that allow missingness to depend on observed or unobserved data. Which assumptions or methods apply cannot be determined from the registry record. The record also does not report covariate adjustment, stratification factors, or other details that might affect estimation. These gaps do not invalidate the posted summaries, but they limit assessment of their robustness and of how closely the simple recalculations correspond to the trial’s planned analysis.

15. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization (8.3%), hopsitalization (4.2%).

The registry lists serious adverse events among participants at risk in each group. Serious events were reported for 3 of 24 participants in the methotrexate group, 2 of 23 in the colchicine group, 0 of 24 in the combination group, and 1 of 23 in the placebo group. The death count is 0 in every group. These are descriptive counts from the registry record; they do not by themselves establish whether an event was caused by a study drug.

The listed serious-event terms include “Hospitalization” at 8.3% and “Hopsitalization” at 4.2%. The latter spelling is reproduced as recorded; the registry does not explain whether the entries refer to distinct categories or reflect a labeling issue. Other adverse events are listed for 22 of 24 participants in the methotrexate group, 21 of 23 in the colchicine group, 23 of 24 in the combination group, and 23 of 23 in the placebo group. The registry record does not provide event-level details, severity distributions beyond the serious classification, attribution, or a statistical comparison between groups. The counts should therefore be read as safety reporting summaries, not as comparative evidence of risk.

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

The primary endpoint results describe average MRI-measured coronary cross-sectional-area change during handgrip exercise at 8 weeks in the groups with posted measurements. The three simple unadjusted comparisons with placebo have intervals that include zero, and the intervals are broad enough to accommodate differences in either direction. The results therefore leave substantial uncertainty about the size and direction of group differences in this endpoint.

This statistical uncertainty is not the same as proof that the groups are identical. A comparison can fail to distinguish a difference clearly when its estimate is imprecise. Nor should the observed point estimates be treated as proof of a difference. The record does not specify a clinically important threshold for this measure, so the posted estimates alone cannot establish whether a difference is meaningful to patients or to clinical practice.

The endpoint is a physiological MRI measure rather than a clinical event. Its meaning is limited to the particular measure, population, groups, and assessment time described in the registry. The record does not report whether changes in this measure predict later clinical outcomes. It also does not report participant-level results, longer-term outcomes, or a complete sponsor analysis that could provide a broader account of the treatment comparisons.

The secondary outcomes add observations about other measures, but they do not eliminate the uncertainty in the primary result. Several secondary results are not posted, and multiplicity handling is not reported. The listed safety counts provide descriptive event information, but the record does not report attribution or comparative safety analyses. Taken together, the registry record supports a cautious reading of the posted statistics: they describe the observed summaries and their uncertainty, but do not by themselves establish a clinical benefit, absence of benefit, or causal explanation.

17. Why This Trial Matters Statistically

This trial is statistically informative because it links a physiological endpoint to several treatment regimens within a randomized, triple-masked, factorial phase 2 design. The group summaries make it possible to see the direction and uncertainty of the primary comparisons, while the four listed groups distinguish single-drug regimens, a combination regimen, and placebo. The design structure raises questions about both treatment-specific comparisons and possible interactions, but the registry record does not report factorial interaction analyses.

The primary outcome illustrates why estimates and uncertainty should be considered together. Each point estimate is one summary of the observed data, whereas the reported intervals show that a range of differences remains compatible with those data. The intervals span zero, and the unadjusted recalculations do not provide a precise account of the comparative effects. This is a useful example of why a single p-value or group mean should not stand in for the full uncertainty assessment.

The record also illustrates the distinction between a trial’s original design and retrospective planning illustrations based on observed effects. The sample-size figures are hypothetical planning quantities, not evidence about the trial’s original assumptions or about power achieved. The original sample-size justification is not reported in the registry record. Similarly, displayed secondary comparisons are not a substitute for a prespecified analysis plan, particularly when multiple endpoints and comparisons are considered.

Finally, differing outcome counts and unreported analysis details matter to interpretation. Clear reporting of participant flow, missing-data handling, analysis populations, multiplicity decisions, and factorial analyses would make it easier to assess the robustness and intended role of each result. The available record offers useful descriptive statistics, but leaves those analytical questions open.

18. 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 constrain interpretation of the registry results. The primary endpoint counts are smaller than the overall enrollment figure, and the counts vary by treatment group. The registry record does not explain the differences, identify reasons for unavailable measurements, or describe how missing data were handled. Without those details, it is not possible to determine whether the posted summaries represent all randomized participants or a subset defined by measurement availability.

The primary comparisons available in the record are simple unadjusted recalculations from group summaries. A sponsor-reported inferential analysis and its model details are not reported. The record does not describe whether the factorial structure was used to estimate main effects or interactions, whether covariates were included, or whether assumptions were checked. It also does not report an analysis population, sensitivity analyses, or a detailed statistical analysis plan.

Multiple outcomes and treatment comparisons are listed, but the record does not report a multiplicity strategy or hierarchy for interpreting tests. Some listed secondary outcomes do not have posted results. The confidence level and method for the reported intervals are not stated, and the original sample-size justification is not reported. The planning illustrations based on observed effects cannot fill that gap.

Finally, the primary outcome is a physiological measure assessed at 8 weeks. The record does not establish how that measure relates to patient-important outcomes or provide a clinically important difference for interpreting its scale. These limitations do not change the values that are posted, but they restrict conclusions about precision, robustness, clinical relevance, and the broader meaning of the comparisons.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Inflammation and Coronary Endothelial Function — NCT02366091.
• Registry record last updated 2021-10-21; status last verified 2021-09.
• Results first posted 2021-10-21.
• 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.

22. Record Summary

The registry describes a completed randomized, triple-masked, factorial phase 2 trial sponsored by Johns Hopkins University, with an enrollment of 111. It studied methotrexate, colchicine, their combination, and placebo in patients with coronary artery disease and abnormal coronary endothelial function. The primary outcome was mean percent change in coronary cross-sectional area during handgrip exercise at 8 weeks.

All three simple unadjusted primary comparisons with placebo have reported intervals that include zero. The registry also reports selected secondary summaries and adverse-event counts, but does not provide a full analysis plan, original sample-size justification, missing-data methods, analysis-population definitions, or multiplicity strategy. The primary estimates are therefore best read with attention to their uncertainty and to the limits of the registry’s analytical detail.