Comparison of Contrast Agents During CT Angiography: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Contrast Agents During CT Angiography (NCT01534975), a randomized na study. The primary outcome is Image Quality of the CT Scans Using Different Contrast Agents.

2. Clinical Question

3. Trial Design

The registry describes a prospective, single-center, double-blind randomized study in subjects undergoing coronary CT angiography. The official title identifies the study as triple-masked, and the design fields describe randomized allocation and a parallel-group model. The registry record does not explain how the masking labels were operationalized or identify which study roles were masked.

The four arms received iodixanol 320, iohexol 350, iopamidol 370, or iodixanol 270 during CT acquisition. The record reports enrollment of 513. The brief summary describes a plan to recruit 400 participants, so that planned figure should be distinguished from the posted enrollment. The registry lists the study as completed, with a start date of 2012-01 and primary completion in 2013-01.

The primary outcome is titled “Image Quality of the CT Scans Using Different Contrast Agents,” with a timeframe of 1 year. The outcome description refers to ascending-aorta attenuation and its standard deviation. The registry lists one outcome measure and no posted analyses. It does not report the trial's original sample-size justification, detailed allocation procedure, or a complete statistical analysis plan.

The brief summary also identifies tolerability, contrast enhancement, heart rate, adverse events, reimaging, costs, and patient satisfaction as areas of interest. However, no secondary outcome results are posted in the registry record. The recorded primary results therefore support interpretation of the reported attenuation measure, but not a comprehensive comparison across all the aims described in the summary.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Image Quality of the CT Scans Using Different Contrast Agents, measured over 1 year.

The primary endpoint is the image-quality measure titled “Image Quality of the CT Scans Using Different Contrast Agents.” Its description specifies attenuation in the ascending aorta, expressed in Hounsfield units (HU), and refers to the standard deviation of aortic attenuation. The posted arm results summarize the endpoint using a mean and standard deviation for each group. The registry describes the outcome timeframe as 1 year.

Attenuation is a quantitative feature of the CT image. Comparing group means can indicate whether the measured average differed among participants assigned to the contrast-agent groups. The standard deviation describes the spread of individual measurements around a group mean; it is not the uncertainty of the mean difference. General statistical context: image-quality measures can characterize one aspect of an imaging examination, but a single quantitative measure does not capture every dimension of image quality, tolerability, safety, or patient experience.

The endpoint is used to address the stated comparison of image quality across contrast agents. The record does not report a threshold defining an acceptable or clinically important difference in HU, nor does it explain whether the standard deviation itself was a separate endpoint or part of the endpoint description. Those details are not reported in the registry record.

7. Results Posted in the Registry

• Iohexol 350: mean 357.00 versus 333.00 on control; difference 24.00 (95% CI 9.28 to 38.72), standardized effect d = 0.39; z-test p = 0.001.
• Iopamidol 370: mean 362.00 versus 333.00 on control; difference 29.00 (95% CI 14.53 to 43.47), standardized effect d = 0.45; z-test p = <0.001.
• Iodixanol 270: mean 288.00 versus 333.00 on control; difference -45.00 (95% CI -61.39 to -28.61), standardized effect d = -0.75; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant's aortic attenuation is measured on a numeric scale, and the registry summarizes each arm by its mean and standard deviation. A mean describes the center of the observed measurements in a group. A standard deviation describes how dispersed those measurements are around that group mean. General statistical context: the standard deviation is a feature of individual-level variability, whereas the standard error describes uncertainty in an estimated quantity such as a group mean. They answer different questions and should not be used interchangeably.

The comparisons report mean differences against iodixanol 320. A mean difference is the comparison-group mean minus the reference-group mean. Thus, a positive estimate indicates a higher observed mean in the comparison group than in iodixanol 320, while a negative estimate indicates a lower mean. The estimates are presented in the endpoint's measurement scale, HU. The registry reports the associated group means and group sizes, as well as pooled standard deviations and standard errors for the group means. It does not report the full analysis procedure used to obtain the posted comparisons.

Each reported comparison includes an interval around the mean difference and an unadjusted p-value. General statistical context: an interval estimate conveys a range of values reasonably compatible with the observed data under a specified statistical procedure. A narrower interval indicates greater precision than a wider interval, all else being equal. A p-value assesses the data against a null model, commonly one that assigns no mean difference, using assumptions of the chosen test. Neither a p-value nor an interval addresses whether a difference is clinically meaningful without a relevant threshold and clinical context. The confidence level, calculation method, and test procedure are not reported in the registry record.

The comparisons are unadjusted in the sense that the reported p-values are identified as unadjusted. There are three posted comparisons with iodixanol 320, arising from a study with four arms. General statistical context: testing several contrasts can increase the chance of at least one small p-value when all null hypotheses hold. A multiplicity procedure may control that risk, but the registry record does not report an adjustment method or a prespecified hierarchy of comparisons. The displayed p-values therefore should not be described as multiplicity-adjusted evidence.

The registry also provides standardized effect-size values and pooled standard deviations. General statistical context: a standardized effect expresses a mean difference relative to a measure of variability, allowing comparisons across scales in some settings. Such a measure does not replace the original-scale estimate, which is usually more directly interpretable for the endpoint. The registry record does not explain the role of the standardized effect estimates in the trial's own analysis plan.

The displayed group summaries and comparisons do not reveal how participants with missing endpoint values were handled, whether all randomized participants were included, or whether the analysis followed assigned groups. The definitions of the analysis populations, any exclusions, and any adjustment for baseline factors are not reported in the registry record. These omissions limit the ability to reconstruct the trial's analysis from the registry results alone.

Over-dispersion is a concern mainly when a model assumes a particular level of variability, such as a count model whose variance may be larger than expected under its assumed distribution. General statistical context: if variability is underestimated, standard errors may be too small and intervals too narrow. This primary endpoint is reported as a continuous measure with standard deviations, not as a count outcome. The registry does not report a model-based analysis or a diagnostic assessment of distributional assumptions, so it is not possible to say how such assumptions were evaluated.

Randomization and masking are stated in the design record, but key implementation details are not reported. The record does not specify the randomization sequence method, concealment procedure, masking roles, or whether the primary analysis accounted for any design features beyond the parallel-arm allocation. These are aspects of the method that cannot be inferred from the posted means and comparisons.

The trial's own statistical analysis plan, interim analyses, and original sample-size justification are not reported in the registry record. The planning illustrations associated with the observed comparisons use separately stated assumptions and should not be mistaken for the original design calculations. Their purpose is to show how planned sample size varies with an assumed effect under those assumptions, not to describe what the trial actually planned at its outset.

10. Confidence Intervals and Precision

The intervals accompanying the mean differences communicate the precision of the estimated comparisons. For iohexol 350 versus iodixanol 320, the estimate is 24.0 HU and the reported interval extends from 9.282 to 38.72. For iopamidol 370 versus iodixanol 320, the estimate is 29.0 HU and the interval extends from 14.53 to 43.47. For iodixanol 270 versus iodixanol 320, the estimate is -45.0 HU and the interval extends from -61.39 to -28.61. The interval endpoints are reported on the HU scale.

General statistical context: an interval is an estimate of uncertainty, not a range containing a fixed proportion of individual participants' values. Its width reflects factors such as the observed variability and the amount of information in the comparison, along with the method used to construct it. The standard deviations reported for the arms describe participant-level spread and should not be confused with the comparison intervals.

Each reported interval lies on one side of zero, the value corresponding to no mean difference. This is consistent with the associated unadjusted p-values, but it does not establish clinical importance. The registry does not report the confidence level or interval-construction method, and the intervals should not be assigned a confidence level based on assumption. It also does not report a clinically important difference threshold for attenuation. As a result, the statistical precision can be described from the endpoints, but the clinical interpretation of their size remains uncertain.

The intervals are for separate comparisons with iodixanol 320. The record does not state whether simultaneous coverage across comparisons was intended, and it does not report multiplicity adjustment. Precision for each individual contrast is therefore distinct from the uncertainty involved in interpreting all comparisons together.

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 for the two-arm contrast being considered, not total events. They are illustrations based on the observed effect, not the trial's original design assumptions; those original assumptions are not reported in the registry record. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. The planning figures do not describe the number enrolled or analyzed in the trial.

The 80% power column gives the planned number of participants per arm under the listed assumptions for a design with 80% power to detect the specified effect. The 90% power column gives the corresponding number per arm for a design with 90% power. In general statistical terms, power is the probability of detecting an effect of the specified size under the assumed model if that effect is present. These numbers are planning illustrations, not observed power.

The effect scenarios are expressed as 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Planning for a smaller effect requires more participants per arm under the same assumptions. Figures vary by comparison because the observed estimates and variability differ across contrasts. The curve represents the relationship between the assumed effect size and the planning sample size under the stated assumptions; it should be interpreted as a design aid rather than as a result of the randomized trial.

The registry does not report the original sample-size justification, its assumptions, or whether the study's actual design targeted a particular power for the primary endpoint. These planning figures cannot establish whether the completed study met its original target or whether any observed comparison had adequate precision for a clinical decision.

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 = 24.000; pooled standard deviation σ = 61.523.
2. n = 2 × (1.96 + 0.842)² × 61.523² / 24.000² = 103.2, rounded up to 104 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 <- 24                      # observed difference in means
sigma <- 61.5227189241521                     # 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(1534975)
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 = 104 (80% power), 139 (90% power)
 75% of observed effect: n per arm = 184 (80% power), 246 (90% power)
 50% of observed effect: n per arm = 413 (80% power), 553 (90% power)
power.t.test: 104.1 
Simulated power at n = 104 per arm: 0.801 (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 posts three mean-difference comparisons, each using iodixanol 320 as the reference group. Their p-values are explicitly unadjusted. No multiplicity adjustment, testing hierarchy, or prespecified primary contrast is reported in the registry record. General statistical context: when multiple comparisons are conducted, the chance of obtaining at least one small p-value can rise, depending on how the tests relate to one another. Adjustment methods can address that issue, but no such method should be assumed when it is not described.

The record lists one primary outcome measure and zero posted analyses. It also lists zero secondary outcomes with posted results. The brief summary mentions other areas of evaluation, but results for those aims are not reported in the registry record. Thus, the available outcome reporting does not provide a full account of the study's planned analysis or all outcomes described in the summary.

Missing outcome data, exclusions, and analysis populations are not reported in the registry record. It is not stated how many participants had measurements available for the primary endpoint, whether the arm counts shown represent all randomized participants or only those with observed measurements, or how missing measurements were handled. The registry also does not identify an intention-to-treat, per-protocol, or other analysis population.

The record does not report interim analyses, stopping rules, covariate adjustment, or sensitivity analyses. These items should not be inferred from the sample-size illustrations or the posted summary statistics. Without those details, readers can describe the reported arm summaries and comparisons, but cannot fully assess the prespecified analysis strategy or the robustness of the results to alternative missing-data and analysis choices.

14. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious-adverse-event counts are 0 in each group: iodixanol 320 had 0 among 136 at risk, iohexol 350 had 0 among 133, iopamidol 370 had 0 among 160, and iodixanol 270 had 0 among 84. The record provides no serious adverse-event terms in its listed terms field. Death counts are not reported in the registry record.

The separate counts for participants affected by other, non-serious adverse events are 98 for iodixanol 320, 122 for iohexol 350, 152 for iopamidol 370, and 52 for iodixanol 270, with the respective at-risk group sizes stated above. These counts describe participants recorded as affected; the registry entry does not give event-specific detail in the posted safety summary.

A count of zero reported serious events is not proof that no serious events could occur, and these figures alone do not establish comparative safety. The record does not provide inferential comparisons for adverse events, detailed event definitions, or follow-up completeness for safety. The brief summary notes that tolerability and adverse events were among the study's interests, but the available counts should be interpreted as registry reporting rather than as a complete safety analysis.

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

The primary outcome results show different observed mean aortic attenuation values across the four contrast-agent groups. Relative to iodixanol 320, the posted unadjusted comparisons estimate higher means for iohexol 350 and iopamidol 370, and a lower mean for iodixanol 270. The reported intervals and p-values describe the statistical uncertainty and evidence for those particular mean comparisons under their analysis assumptions. They do not, by themselves, establish which image quality is preferable or whether the magnitude of a difference matters clinically.

The measure concerns attenuation in the ascending aorta. It is not a complete evaluation of diagnostic accuracy, image interpretability, patient satisfaction, tolerability, or cost. The brief summary describes these and other study interests, but secondary results are not posted in the registry record. No conclusions about those outcomes can be drawn from the primary endpoint results alone.

The registry identifies a randomized design, but it does not report enough detail to assess all features of conduct and analysis, including missing-data handling, analysis populations, and multiplicity procedures. The p-values are unadjusted, and the record does not report a clinically important difference threshold. Statistical evidence for a nonzero mean difference is therefore not equivalent to evidence that the difference is clinically meaningful.

The serious-adverse-event counts are zero in each arm, while non-serious adverse events are recorded in all groups. These data do not establish that serious events are impossible, nor do the counts alone determine whether one agent is safer than another. The registry safety record lacks detailed event descriptions and comparative analyses. Overall, the posted results describe the measured image attenuation and recorded adverse-event counts, while important questions about clinical interpretation and the broader study aims remain unanswered in the registry record.

16. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can produce distinct kinds of statistical information. Group means describe the observed endpoint, mean differences express the contrast on its original HU scale, and intervals convey uncertainty around those estimates. Reading these together is more informative than relying on a p-value alone: the estimate gives direction and magnitude, while the interval shows a range of values compatible with the data under the method used.

It also illustrates why an endpoint's meaning matters. Aortic attenuation is a quantitative imaging characteristic, but a statistical difference in that measure is not automatically a difference in overall image quality or clinical usefulness. The registry summary identifies additional study aims, yet no secondary results are posted. Keeping the claims tied to the measured endpoint avoids extending one outcome to broader questions the record does not answer.

The comparison structure raises a familiar issue in multi-arm studies: several treatment contrasts may be of interest, but interpretation depends on whether and how those contrasts were prioritized or adjusted for multiplicity. The available p-values are unadjusted, and no analysis hierarchy is reported. This makes it important to distinguish individual contrast results from a conclusion about all agents considered together.

The planning illustrations also demonstrate that sample-size requirements depend on the effect being targeted and the assumptions used. Smaller target effects require more participants under the same planning framework. Because the original sample-size rationale is not reported, the illustrations cannot stand in for the trial's design justification or establish whether the study was designed around a particular clinically meaningful difference.

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.

The registry record leaves several trial-specific questions unanswered. It gives the randomized, parallel design and describes the study as prospective and single-center, but it does not report the randomization sequence method, allocation concealment, or the practical details of masking. It also does not give participant eligibility criteria beyond the description of subjects undergoing CCTA.

The primary outcome description refers to ascending-aorta attenuation and its standard deviation, but the record does not clarify whether the standard deviation was a separate endpoint, explain how image measurements were taken, or report a threshold for a meaningful difference. The timeframe is listed as 1 year, without further detail about when the endpoint was measured within that period.

For the posted comparisons, the registry does not specify the interval confidence level, interval construction, hypothesis test, handling of missing observations, analysis population, or any covariate adjustment. It does not report multiplicity control, interim analyses, or the original sample-size justification. The available mean and standard-deviation summaries cannot resolve those uncertainties.

The record reports no secondary outcome results, even though the study summary describes multiple additional aims. The safety summary gives counts but not event-specific descriptions or comparative analyses; death counts are not reported in the registry record. The study is identified as single-center, so the record itself does not establish how well results would generalize to other settings. These limitations do not erase the posted endpoint results, but they constrain how broadly and precisely they can be interpreted.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Comparison of Contrast Agents During CT Angiography — NCT01534975.
• Registry record last updated 2018-03-01; status last verified 2017-03.
• Results first posted 2018-03-01.
• 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

NCT01534975 is a completed, randomized, parallel-group study of contrast agents used during coronary CT angiography. The registry describes a prospective, single-center study and identifies the masking as triple. Enrollment is recorded as 513; the brief summary describes a plan to recruit 400 participants. The start date is 2012-01 and primary completion is 2013-01.

The primary outcome is image quality measured through ascending-aorta attenuation in HU. Results are posted for iodixanol 320, iohexol 350, iopamidol 370, and iodixanol 270, with comparisons against iodixanol 320. The registry reports unadjusted p-values and intervals for the mean differences, but does not report the interval method or multiplicity adjustment. No secondary results are posted. Serious adverse-event counts are 0 in each arm; non-serious affected-participant counts are also recorded. The registry does not report the original sample-size justification, analysis populations, or missing-data procedures.