Trial to Assess Chelation Therapy (TACT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial to Assess Chelation Therapy (TACT) (NCT00044213), a randomized phase 3 study. The primary outcome is A Composite of Total Mortality, Recurrent Myocardial Infarction, Stroke, Coronary Revascularization, and Hospitalization for Angina..

2. Clinical Question

3. Trial Design

This was a phase 3 randomized, double-masked trial with a factorial model. The registry record lists 1708 participants and describes four combinations of EDTA and high-dose vitamin treatment: both active, active EDTA with vitamin placebo, EDTA placebo with active vitamins, and both placebos. The arm descriptions specify 40 infusions for the active EDTA and EDTA placebo assignments. The registry record identifies oral high-dose vitamins and their placebo as the other component.

A factorial design organizes assignments across more than one treatment component. It can support comparisons of combinations and, when analyzed as planned, estimates of component effects. The comparisons posted in this record are pairwise comparisons against the EDTA plus high-dose vitamin placebo arm. They should be read as those specific arm comparisons, not as reported main-effect estimates for EDTA or vitamins. The registry record does not report a factorial model analysis or details of how any component effects were estimated.

The primary outcome is a participant count for a composite clinical endpoint, not a time-to-event estimate. The record states that events were centrally adjudicated where available and otherwise site reported. Follow-up was measured over a maximum 5-year period, with a 55 month median. The trial is marked completed. Its listed start is 2003-09 and primary completion is 2011-10.

Randomization helps balance factors that may affect outcomes across assignment groups, while masking is intended to limit influences of treatment knowledge on care or outcome assessment. Those are general purposes of these design features; the registry record does not report allocation concealment procedures, masking success, or further operational 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 A Composite of Total Mortality, Recurrent Myocardial Infarction, Stroke, Coronary Revascularization, and Hospitalization for Angina., measured over Measured over a maximum 5-year follow-up period- 55 month median.

The primary endpoint counts participants with an event in a composite of total mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina. Combining several clinically important outcomes can capture a broader range of events than any single component and can increase the number of participants contributing an endpoint event. It also means that the composite result does not reveal, by itself, whether the components had similar patterns or which component contributed most. Component-level primary results are not reported in the registry record.

The registry describes the measure as the number of patients with events and states that events were centrally adjudicated where available; otherwise site-reported events were used. This endpoint is therefore presented as a binary outcome for each participant: an event was recorded or was not recorded during the stated follow-up. The record gives a maximum 5-year follow-up period and a 55 month median. These time details describe the observation period; the posted arm counts are not event rates per unit of follow-up time.

Composite endpoints are useful when a trial seeks to assess a range of related clinical outcomes, but interpretation depends on the components and their clinical importance. The registry record does not provide separate component counts or a definition of how multiple events within one participant were handled. The posted comparison is consequently best understood as a comparison of participants with at least one qualifying composite event, as described by the record, rather than as a result for any one component.

7. Results Posted in the Registry

• EDTA + High Dose Vitamin: 25.7% (108/421) versus 27.3% (114/418) on control; risk difference -1.6 percentage points (95% CI -7.6 to 4.3), risk ratio 0.94 (0.75–1.18); unadjusted two-proportion z-test p = 0.595.
• EDTA Placebo + High Dose Vitamin: 28.2% (122/432) versus 27.3% (114/418) on control; risk difference 1.0 percentage points (95% CI -5.1 to 7.0), risk ratio 1.04 (0.83–1.29); unadjusted two-proportion z-test p = 0.753.
• EDTA Placebo + High Dose Vitamin Placebo: 31.8% (139/437) versus 27.3% (114/418) on control; risk difference 4.5 percentage points (95% CI -1.6 to 10.6), risk ratio 1.17 (0.95–1.44); unadjusted two-proportion z-test p = 0.146.

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.

A Composite of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke.

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • EDTA + High Dose Vitamin: 9.3% (39/421) versus 13.6% (57/418) on control; risk difference -4.4 percentage points (95% CI -8.7 to -0.1), risk ratio 0.68 (0.46–1.00); unadjusted two-proportion z-test p = 0.047.
  • EDTA Placebo + High Dose Vitamin: 12.7% (55/432) versus 13.6% (57/418) on control; risk difference -0.9 percentage points (95% CI -5.5 to 3.6), risk ratio 0.93 (0.66–1.32); unadjusted two-proportion z-test p = 0.697.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for EDTA + High Dose Vitamin than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between EDTA Placebo + High Dose Vitamin and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts one secondary endpoint, a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Its overall pattern is mixed across the two listed comparisons: the EDTA plus high-dose vitamin comparison has a risk difference below zero with an interval that narrowly excludes zero, while the EDTA placebo plus high-dose vitamin comparison is close to zero and its interval includes zero. These results do not form a consistent pattern across the posted comparisons.

The secondary outcome overlaps conceptually with the primary composite because both include myocardial infarction and cardiovascular events, but the endpoints are not identical. The primary composite also includes total mortality, coronary revascularization, and hospitalization for angina; the secondary composite specifies cardiovascular death and excludes those other components. Different composites can consequently show different patterns without contradiction. The registry record does not report separate counts for individual components, so it is not possible to determine which events account for the observed secondary comparison.

The secondary endpoint does not replace the primary result. The primary comparisons have intervals that include zero, while one secondary comparison has an interval narrowly below zero. Since the secondary result is unadjusted, it is less persuasive as stand-alone evidence when multiple outcomes or comparisons may be examined. General explanation: testing multiple hypotheses increases the chance that at least one result will appear unusual by chance; adjustment methods can address this, but no such method is reported in the registry record.

The record does not report a prespecified hierarchy among secondary outcomes, a multiplicity plan, or analyses beyond the posted counts and unadjusted comparisons. The appropriate overall reading is therefore that the secondary endpoint offers a limited, uncertain signal in one arm comparison, with no matching pattern in the other posted comparison. It should be interpreted alongside, rather than in place of, the primary endpoint and the trial's reporting limitations.

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

• A Composite of Cardiovascular Death, Non-fatal Myocardial Infarction and Non-fatal Stroke.

9. Statistical Interpretation

10. Statistical Methods Explained

The posted outcome is a binary participant-level count: each participant is classified according to whether the specified composite event was recorded during follow-up. The comparisons express the difference in observed event proportions as a risk difference. General explanation: a risk difference is the event proportion in one group minus the event proportion in the reference group. A value below zero indicates a lower observed proportion in the listed comparison group; a value above zero indicates a higher observed proportion. It is an absolute contrast, not a relative percentage change.

What do the confidence intervals describe?

Each confidence interval gives a range of values compatible with the observed data under the calculation method. General explanation: a confidence interval conveys uncertainty around an estimate; it is not a guarantee that the true effect lies within that particular interval. For the primary comparisons, each reported interval spans zero, so the data are compatible with no risk difference as well as differences in either direction. The secondary EDTA plus high-dose vitamin interval runs from -0.087 to -0.001, narrowly excluding zero. That interval describes the unadjusted comparison and does not account for the fact that multiple outcomes and comparisons may be considered.

How should the p-values be read?

The registry lists unadjusted p-values. General explanation: a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that null hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The posted values should be considered alongside the estimates and intervals. A small p-value does not remove uncertainty, and a larger p-value does not establish equivalence or prove that groups are identical.

What does factorial assignment add?

The four arms combine active or placebo EDTA with active or placebo high-dose vitamins. This is a factorial arrangement. In general, factorial trials can estimate effects of separate components efficiently when their design and analysis support those estimates. The displayed comparisons are instead individual arm comparisons against the EDTA plus high-dose vitamin placebo arm. They do not, on their own, report an overall EDTA effect, an overall vitamin effect, or an interaction between components. The registry record does not report a factorial analysis plan or those estimates.

What can be learned from event counts?

Counts make the number of participants with recorded events visible, while group sizes show the denominator for each arm. Because group sizes differ, the comparison uses proportions rather than comparing raw event counts alone. General explanation: a participant count does not account for differing follow-up duration in the way a time-to-event analysis might. The record gives a maximum 5-year follow-up period and a 55 month median but does not provide a time-to-event estimate in the posted primary results.

What analysis details are missing?

The record reports no analyses in its reported-analyses listing. It does not describe the original statistical plan, the analysis population, handling of missing outcome data, covariate adjustment, or any multiplicity adjustment. These details matter because analysis choices can influence uncertainty and the interpretation of several outcomes or comparisons. The counts and unadjusted calculations should therefore be read as the results posted in the registry, not as a complete account of the trial's statistical analysis.

In general, random assignment supports comparisons because assignment is not chosen in response to participants' expected outcomes. However, randomization does not eliminate chance variation, missing-data concerns, or limitations from incomplete reporting. The registry record's description of central adjudication where available and site reporting otherwise is relevant to outcome ascertainment, but it does not give the proportion assessed by each route or further details about adjudication procedures.

11. Confidence Intervals and Precision

Precision concerns how tightly the data locate an effect estimate. The primary risk-difference intervals are -0.076 to 0.043 for EDTA plus high-dose vitamin versus its reference, -0.051 to 0.070 for EDTA placebo plus high-dose vitamin versus its reference, and -0.016 to 0.106 for the placebo combination versus the reference. Each interval includes zero. Their ranges also allow differences in both directions, so the point estimates should not be treated as precise measurements of a single underlying effect.

The secondary comparison of EDTA plus high-dose vitamin with the reference has an interval from -0.087 to -0.001. It excludes zero by a narrow margin, while the other posted secondary comparison has an interval from -0.055 to 0.036, which includes zero. The interval width reflects uncertainty in each arm comparison; the different outcome and its secondary status also matter for interpretation.

General explanation: confidence intervals tend to be narrower when the data contain more information and wider when estimates are less precise. They describe uncertainty under the calculation assumptions and do not incorporate every possible source of bias, such as missing data or outcome ascertainment concerns. The registry record does not report adjusted confidence intervals or a multiplicity correction. These intervals therefore describe the posted unadjusted comparisons and should not be read as if they account for all trial-level uncertainty.

Precision is not the same as clinical importance. A relatively small interval may still cover effects whose importance depends on the outcome and context, while an interval spanning zero does not prove that no meaningful difference exists. The registry record does not provide a threshold for a clinically important difference, so the posted estimates cannot be classified against such a threshold.

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 sample-size figures are planning illustrations based on the observed effect, not the trial's original design assumptions. For these binary outcomes, the figures are participants per arm, not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect. The trial's own original sample-size assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm that the illustration estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column gives the corresponding planning target for a 90% chance. These are design concepts, not guarantees that a study will detect an effect. The illustration is not observed power.

Read each row as a different assumed effect size: planning for 100% of the observed effect, planning for 75% of the observed effect, or planning for 50% of the observed effect. Smaller effects require more participants to distinguish them from random variation under the stated assumptions. The displayed values vary substantially across comparisons because the observed effects differ; that variation does not mean the trial was designed with those targets.

A sample-size curve represents the same planning relationship visually: as the effect to detect becomes smaller, the required number of participants rises. These calculations assume a simplified two-arm comparison and do not reproduce the trial's four-arm factorial design or account for unreported analysis features. They are therefore useful as illustrations of statistical planning, not as a retrospective judgment about the trial's adequacy.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.273; treatment proportion p₁ = 0.257; average p̄ = 0.265.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6239 = 1.2227.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6238 = 0.5250.
4. n = (1.2227 + 0.5250)² / (-0.0162)² = 11,645.7, rounded up to 11,646 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
p0 <- 0.272727272727273                          # control proportion
p1 <- 0.256532066508314                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(44213)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 11,646 (80% power), 15,590 (90% power)
 75% of observed effect: n per arm = 20,806 (80% power), 27,852 (90% power)
 50% of observed effect: n per arm = 47,039 (80% power), 62,971 (90% power)
power.prop.test: 11645.7 
Simulated power at n = 11,646 per arm: 0.803 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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

Multiplicity arises when results are examined across several outcomes, treatment comparisons, or analyses. The more questions assessed, the greater the chance that at least one result may look unusual even when there is no underlying effect. General explanation: prespecified testing strategies or statistical adjustments can help control that risk. The registry record does not report a multiplicity procedure, an outcome hierarchy, or whether the posted comparisons were prespecified in the trial analysis plan.

This matters particularly because the primary endpoint has several arm comparisons and the secondary endpoint has additional comparisons. The secondary EDTA plus high-dose vitamin comparison has an unadjusted p-value of 0.047 and an interval narrowly excluding zero. Without a reported multiplicity approach, that result should be treated cautiously. It cannot be interpreted as though it were the only hypothesis tested.

The reported-analyses listing is empty. The registry record does not report whether analyses followed an intention-to-treat population, how participants with missing outcome data were handled, or whether exclusions occurred. It also does not report imputation, sensitivity analyses, covariate adjustments, or a detailed statistical analysis plan. These omissions do not establish that the trial lacked such procedures; they mean they are not reported in the registry record.

The record indicates that events were centrally adjudicated where available and otherwise site reported, but it does not state how many events were assessed by each method or give further information about missing assessments. It also does not report the number of participants with incomplete follow-up or the treatment of withdrawals. Without these details, the posted counts cannot show whether missingness or differences in ascertainment could have affected comparisons.

These reporting gaps limit the ability to reconstruct the full inferential process. The posted event counts and unadjusted comparisons remain interpretable as registry results, but their evidential strength depends on analysis and data-handling details that are not reported in the registry record.

15. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure congestive (0.5%), malaise (0.2%), cardio-respiratory arrest (0.2%).

The adverse-event record lists serious adverse events for each treatment combination. The counts are 2 among 421 participants in the EDTA plus high-dose vitamin arm, 0 among 418 in the EDTA plus high-dose vitamin placebo arm, 0 among 432 in the EDTA placebo plus high-dose vitamin arm, and 2 among 437 in the EDTA placebo plus high-dose vitamin placebo arm. These are reported counts, not estimates of comparative risk adjusted for follow-up or other factors. The record does not provide deaths in these adverse-event groups.

The registry also lists other adverse events, with counts of 168, 201, 164, and 185 for the four arms in the same order. Those counts are distinct from the serious adverse-event counts and should not be combined with them. Listed serious-event terms include cardiac failure congestive at 0.5%, malaise at 0.2%, and cardio-respiratory arrest at 0.2%. The record does not give enough detail to attribute any event to a treatment or to compare event severity, timing, or duration.

These safety figures describe what was posted for the arms. They do not establish that a treatment caused or prevented an adverse event, and the registry record does not report a formal comparative safety analysis.

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

The posted primary results describe participant counts for a composite outcome, together with unadjusted comparisons against the EDTA plus high-dose vitamin placebo arm. All primary risk-difference intervals include zero. This means the posted estimates are uncertain and compatible with no difference as well as differences in either direction. It does not show that the groups are equivalent, and it does not establish that a treatment combination is ineffective.

One secondary comparison has a risk-difference interval narrowly below zero, but the other posted secondary comparison does not show the same pattern. The secondary endpoint is different from the primary composite, and the registry record does not report multiplicity adjustment. This result therefore should not be elevated above the primary outcome or treated as a definitive finding.

The comparisons are between specific treatment combinations and a designated reference arm. They are not reported main effects for EDTA or vitamins, and they do not establish whether the components interact. The factorial structure is important context, but the registry record does not supply a factorial analysis that would answer those component-level questions.

The results also do not provide a complete account of how the trial analyzed its data. The analysis population, missing-data handling, original statistical plan, and multiplicity approach are not reported in the registry record. Nor are separate results for the primary composite's components. These omissions limit conclusions about robustness and about which outcomes contributed to the composite patterns.

In general, trial results are estimates rather than certainties. The posted counts and intervals can describe observed differences and their statistical precision, but they do not by themselves establish causation, clinical importance, or a recommendation for care. The registry record does not report a threshold for clinical importance. The appropriate reading is bounded: the primary comparisons are inconclusive about differences, and the secondary pattern warrants caution.

17. Why This Trial Matters Statistically

This trial is statistically notable for its factorial structure and for the way its registry results are presented. Four arms combine active and placebo assignments for EDTA and high-dose vitamins, while the listed comparisons use one combination as the reference. This distinction matters: comparisons of individual combinations do not automatically answer the broader question of each component's average effect or whether the components interact.

The primary outcome is a composite, which can represent several kinds of clinically important events in one participant-level measure. A composite can improve the amount of information available for comparison, but it can also conceal different patterns among its components. Because separate component results are not reported in the registry record, the primary composite cannot identify which event types contributed to the arm counts.

The results also illustrate why estimates should be read with confidence intervals rather than p-values alone. The primary risk-difference intervals include zero and allow effects in both directions. A secondary comparison has an interval narrowly excluding zero, yet it is unadjusted and sits within a set of outcome and arm comparisons. Statistical interpretation depends not just on a threshold but on precision, multiplicity, outcome priority, and the analysis plan.

Finally, the registry record gives useful design and outcome information but leaves important analysis details unreported. The sample-size illustrations are based on observed effects and are not the original design calculations. Distinguishing planning illustrations from trial design assumptions, and registry comparisons from a full statistical analysis, helps keep conclusions aligned with what the record actually documents.

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 are specific to the posted registry results. First, the reported primary endpoint is a composite, but separate counts for total mortality, recurrent myocardial infarction, stroke, coronary revascularization, and hospitalization for angina are not reported. The record therefore does not show whether the overall event-count pattern was shared by the components or mainly reflected one component.

Second, although the trial used a factorial design, the posted comparisons are arm-to-reference comparisons. Main-effect estimates for EDTA and high-dose vitamins, and any interaction estimate, are not reported in the registry record. The results cannot be used to infer those effects from the listed comparisons alone.

Third, the analyses are unadjusted and no multiplicity method is reported. The record also does not report the original analysis plan, analysis population, missing-data handling, covariate adjustment, or sensitivity analyses. This limits the ability to assess whether the posted results reflect the prespecified analysis and how robust the estimates are to analytic choices.

Fourth, follow-up is described as a maximum 5-year period with a 55 month median, but the posted primary comparisons are participant counts rather than time-to-event estimates. The record does not provide detailed follow-up completeness or explain the treatment of incomplete observation. It also does not state how many events were centrally adjudicated versus site reported.

Finally, the adverse-event record gives counts but not comparative analyses, attribution, timing, or duration. These limitations do not invalidate the posted results; they constrain what can be concluded from the registry record alone.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Trial to Assess Chelation Therapy (TACT) — NCT00044213.
• Registry record last updated 2013-11-05; status last verified 2013-08.
• Results first posted 2013-11-05.
• 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.

22. Record Summary

The registry describes TACT as a completed, randomized, double-masked, phase 3 factorial trial in coronary artery disease, with 1708 participants. The four treatment combinations paired active or placebo EDTA with active or placebo high-dose vitamins. The primary endpoint counted participants with a composite of total mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina, over a maximum 5-year follow-up period with a 55 month median.

The posted primary arm comparisons have risk-difference confidence intervals that include zero. One unadjusted secondary comparison has an interval narrowly excluding zero, while the other includes zero. These findings require caution because multiplicity and detailed analysis procedures are not reported in the registry record. The record also posts adverse-event counts but no formal comparative safety analysis.