Coronary MDCTA With Iopamidol Injection 370: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Coronary MDCTA With Iopamidol Injection 370 (NCT00558792), a randomized phase 2 study. The primary outcome is Diagnostic Quality of Visualization of Coronary Arteries, Off-Site Reader 1.

2. Clinical Question

The study’s stated purpose was to determine the validity of arterial-segment visualization and compare visualization after the three doses, with the aim of identifying a dose for further investigation in future trials. That is a diagnostic-image-quality question. The primary outcome concerns the reader’s assessment of image visualization, rather than a clinical outcome or a direct measure of stenosis itself.

The record does not report a prespecified pairwise question, such as whether one particular dose differs from another. Nor does it provide a clinical threshold for a meaningful difference in visualization. The reported overall test can indicate evidence of variation across the three groups, but it does not by itself establish which groups differ or whether any difference would be important for diagnosis.

3. Trial Design

This was a completed Phase II, randomized, triple-masked, parallel-group study sponsored by Bracco Diagnostics, Inc. The registry lists an enrollment of 210 participants. The study start is recorded as 2007-11 and primary completion as 2010-05.

Participants were assigned to one of three iopamidol injection 370 groups: Isovue 370, 70 mL; Isovue 370, 80 mL; or Isovue 370, 90 mL. The registry describes the allocation as randomized and the design as parallel. It identifies masking as triple, but the identities of the groups of people who were masked and the procedures used to maintain masking are not reported in the registry record.

The primary outcome was assessed immediately post dose by off-site reader 1. The outcome description applies to technically adequate coronary artery segments and concerns whether each segment’s visualization was adequate for accurate diagnosis of the presence and severity of stenosis. The record also lists a secondary outcome concerning participants who experienced adverse events with incidence of 5% or greater.

The registry lists 13 outcome measures and 24 analyses. It does not report the detailed eligibility criteria, the distribution of all randomized participants through follow-up, or whether the reported group counts correspond to an intention-to-treat or another analysis population. The method used to generate the random sequence, allocation concealment procedures, and detailed masking procedures are not reported in the registry record. These omissions limit assessment of how the design was implemented, even though the record identifies the broad design as randomized, triple-masked, and parallel-group.

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: This was a Phase II, multicenter, prospective, double-blind, randomized, parallel-group comparison of 3 doses of iopamidol injection 370 when used for coronary MDCTA.

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 Diagnostic Quality of Visualization of Coronary Arteries, Off-Site Reader 1, measured over Immediately post dose.

The primary endpoint is the number of coronary artery segments visualized accurately, assessed by off-site reader 1 immediately post dose. The assessment was restricted to technically adequate segments. For each segment, the reader considered whether image quality was adequate for accurate diagnosis of the presence and severity of coronary artery stenosis.

The registry describes two features of adequate visualization: no more than mild blurring of the spatial distinction between the vessel wall and lumen, and a readily visible image-contrast distinction between calcified plaque, enhanced vessel lumen, and uncalcified vessel wall or plaque. In this way, the endpoint represents a reader-based assessment of image quality relevant to interpreting the coronary arteries, rather than a count of clinical events.

Such an endpoint is used to compare how the dose groups perform on the study’s stated imaging task. However, the registry reports counts of segments visualized accurately, not the total number of technically adequate segments assessed in each group or a proportion of segments meeting the criteria. Without those denominators, the counts alone do not show the share of assessed segments judged adequate. The endpoint description also does not report how disagreements between readers were handled; the posted primary result is specifically for off-site reader 1.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a chi-squared analysis comparing the three dose groups for the primary count outcome and gives p = 0.010. Other details needed to reproduce or fully assess the analysis are not reported in the registry record. General explanations below describe the statistical concepts, not additional findings from the study.

What does an overall chi-squared test address?

In general, a chi-squared test assesses whether observed categorical counts are compatible with a specified pattern under a null hypothesis. For a comparison involving several groups, an overall result can indicate that the pattern is not consistent with the null model. It does not, by itself, state which pair of groups accounts for that result. Pairwise comparisons or other follow-up analyses are needed to answer that more specific question, and their results and multiplicity handling are not reported in the registry record.

The registry identifies the endpoint as a number of segments visualized accurately, but does not provide the full contingency table or the total segments assessed in each arm. It is therefore not possible to determine from the posted information exactly what counts entered the chi-squared calculation, how the outcome was represented for the test, or whether any assumptions were checked. The test label and p-value should be reported as the registry gives them, without inferring an unreported model specification.

Why do denominators matter for counts?

As a general statistical principle, a count depends on both the frequency of an event and the amount of opportunity to observe it. If groups contribute different numbers of segments, a larger count of accurately visualized segments need not correspond to a larger proportion meeting the quality criterion. The registry reports participant counts and counts of segments visualized accurately, but not the number of segments assessed in each group. It also does not describe whether the number of segments contributed per participant was similar across groups.

That missing denominator prevents calculation or interpretation of a group-specific percentage from the registry record. No percentage or rate should be inferred from the posted counts. In addition, multiple segments may belong to one participant. In general, measurements from the same participant can be correlated, and methods that treat all segments as independent may not reflect that dependence. The registry does not report whether the analysis accounted for clustering of segments within participants.

What does the p-value say, and what does it not say?

In general, a p-value is calculated under a null hypothesis and a model for the data. It quantifies how unusual data at least as incompatible with that null model would be if the model were correct. It does not give the probability that the null hypothesis is true, quantify the size of an effect, or establish that a result is clinically important. The reported p = 0.010 is the result of the registry’s stated three-group chi-squared analysis. The record does not include a confidence interval or a measure of effect size for that analysis, so precision and magnitude cannot be assessed from the p-value alone.

A confidence interval, in general, gives a range of values compatible with an estimation procedure and its assumptions. It helps convey uncertainty about an effect estimate. No interval is reported for this primary result. The registry also does not report the effect measure, detailed test inputs, or a prespecified threshold for an important difference in visualization.

How should the planning illustrations be understood?

Sample-size illustrations, when based on an observed effect, are planning calculations rather than observed trial outcomes. In general, such calculations estimate the participants per arm that would be needed under stated assumptions to detect a specified fraction of an observed effect at a chosen significance level and power, using the stated allocation and approximation. Those assumptions do not describe what the trial actually achieved and should not be called observed power. The registry record does not report the trial’s own sample-size justification, so an illustration based on the observed result cannot establish the original design rationale or the study’s planned detectable effect.

The stated illustration assumptions refer to a two-sided significance level of 0.05, equal allocation, and a normal approximation. The trial itself has three arms and the posted analysis is an overall chi-squared test; an illustration based on a two-arm comparison is not the same analysis as the trial’s reported three-group test. The record does not provide a valid two-arm comparison for this count outcome, and no pairwise recalculation should be inferred from the overall test.

What analysis details remain unavailable?

The statistical analysis plan, analysis population, handling of missing outcome data, and treatment of multiple outcomes are not reported in the registry record. Nor are the chi-squared test’s detailed construction, diagnostic checks, or any adjustment for participant-level clustering described. These details matter for interpreting whether the reported test matches the endpoint structure and how much confidence to place in the result. The registry gives the method label and the overall p-value, but not enough information to reconstruct the analysis independently.

10. Analyses Reported by the Sponsor

The registry’s posted primary analysis is a chi-squared test across the three dose groups, with p = 0.010. It is an overall test; the record does not provide a separate sponsor-reported result for each pair of doses or a confidence interval for a dose contrast.

No discrepancy is flagged between the posted analysis and the registry information. The count endpoint is not reduced to a single two-arm comparison, and the registry does not provide the inputs needed to recalculate a valid pairwise comparison from the posted summary statistics. Accordingly, there is no recalculated pairwise estimate to set against the sponsor’s analysis. The sponsor’s reported overall analysis remains the result to describe, while its interpretation is limited by the lack of denominators, effect estimates, and details of the analysis population and model.

In general, a simple recalculation from summary statistics can serve as a check only when the summary statistics support the same comparison and estimand. It cannot replace an analysis that depends on unreported participant-level or segment-level information. Here, the available information does not establish whether segments within a participant were treated as related observations, or exactly how the chi-squared test was constructed. The reported p-value should therefore be presented as the registry’s analysis rather than as an independently reproduced result.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 24 analyses, and one secondary outcome is posted: the number of participants who experienced adverse events with incidence of 5% or greater. The number of outcomes and analyses indicates that the record includes multiple statistical questions, but it does not establish how those questions were prioritized or handled in inference.

When many outcomes, groups, or analyses are examined, the chance of at least one apparently notable result can increase. As a general statistical approach, investigators may prespecify a primary comparison, adjust for multiple testing, or use a hierarchy of tests. The registry does not report whether any such approach was planned or used, whether the posted p-value was adjusted, or whether the outcome and analysis hierarchy was prespecified. It is therefore not possible to characterize p = 0.010 as adjusted or unadjusted based on the registry record.

The primary endpoint is described for off-site reader 1, but the record does not explain how results from other readers, if any, were incorporated into the full analysis. It does not report whether reader-specific results were considered multiple analyses or how reader agreement was assessed. The registry lists 24 analyses, but the full analysis plan and the relationship among those analyses are not reported in the registry record.

Missing-data handling and analysis populations are also not reported. The record gives participant counts for the primary result, but does not state whether these are all randomized participants, participants with evaluable imaging, or another analysis set. It does not report how technically inadequate segments, unreadable images, or participants lacking an endpoint assessment were handled. The enrollment figure alone does not clarify this flow.

Without the multiplicity plan, missing-data procedures, and analysis-population definition, the p-value cannot be evaluated in the context of all planned analyses, and the scope of the analyzed data is uncertain. These are reporting limitations, not evidence that a particular method was or was not used.

12. 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 non-serious adverse event terms

The registry reports zero participants with serious adverse events in each dose group. The numbers at risk are 68 for 70 mL, 63 for 80 mL, and 60 for 90 mL. The record does not list serious adverse-event terms for these groups.

These figures describe the events posted in the registry record; they do not establish that the underlying risk was zero. In general, an observed zero count is compatible with uncertainty about uncommon events, particularly when the number of participants observed is limited. The registry does not report a confidence interval or further detail on the observation period and ascertainment for serious adverse events, so the precision of these safety counts cannot be quantified from the record.

The record separately lists other adverse events affecting 15 participants in the 70 mL group, 14 in the 80 mL group, and 13 in the 90 mL group. Those are not the serious-event counts and should not be combined with them. The posted secondary outcome concerns adverse events with incidence of 5% or greater, but the record does not provide event terms or a detailed account of severity and timing in the information available for this result.

Safety counts are descriptive within this trial. They do not, by themselves, establish comparative safety between doses, particularly without a stated statistical comparison, event definitions, exposure details, or uncertainty estimates.

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

The registry record describes a randomized comparison of three iopamidol doses and reports an overall chi-squared result for the number of coronary artery segments judged accurately visualized by off-site reader 1. The posted p-value is 0.010. The segment counts are 949 for 70 mL, 842 for 80 mL, and 841 for 90 mL. These numbers describe counts, not proportions of all segments assessed.

As a general interpretation, the overall statistical result addresses whether the observed pattern across the three groups is compatible with the test’s null model. It does not identify which dose comparisons differ. It also does not measure how large or important any difference is. The absence of total assessed-segment denominators, pairwise effect estimates, and confidence intervals leaves the magnitude and precision of a dose contrast unclear.

The endpoint captures a reader’s assessment of image visualization against the registry’s stated image-quality features. It does not directly report diagnostic accuracy against a reference standard, clinical outcomes, or whether a diagnosis changed. The result is specific to the immediate post-dose assessment and off-site reader 1 as described in the registry.

The record’s stated aim was to compare visualization and determine a dose for further investigation in future trials. The posted analysis can be read as an overall statistical finding within that imaging assessment, but it does not alone establish a preferred dose or show that a particular difference is clinically meaningful. The missing denominator and analysis details also prevent a full assessment of the assumptions behind the test.

The adverse-event figures are likewise limited: the registry reports zero serious adverse events in each group during the reported study, but these counts do not prove the absence of risk. Taken together, the results describe the posted imaging counts, an overall test, and event counts in this study. They should not be extended beyond those measurements and the information recorded.

14. Why This Trial Matters Statistically

This study is statistically instructive because its primary outcome is a count of image segments, while the randomized units are participants. Those units are not necessarily interchangeable: participants can contribute segments, and the registry does not report the total number of segments assessed in each group. Without those denominators, raw segment counts do not directly express the fraction of segments meeting the visualization criteria.

The study also illustrates the distinction between an overall test and a set of dose-specific comparisons. The registry reports a chi-squared result across three groups, but an overall p-value does not reveal which pair of doses differs or provide an estimate of the size and precision of a particular contrast. Interpretation therefore depends not only on statistical significance, but also on the outcome scale, denominators, and the analysis question.

Another important issue is the structure of the observations. In general, multiple segments from one participant may be correlated. The registry does not describe whether the analysis accounts for that possibility. The test label alone does not resolve how segment-level observations were handled or whether the method matched the data structure.

Finally, this Phase II study was intended to compare visualization across doses and identify a dose for further investigation. The record does not report the sample-size justification or a multiplicity plan. Its results are most useful as a record of the imaging outcome and the analysis reported, with important uncertainty about denominators and analytic details. This example shows why a p-value is only one part of a statistical interpretation.

15. 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 does not report the total number of technically adequate coronary artery segments assessed in each dose group. Because the primary outcome is a count of segments judged accurately visualized, that missing denominator prevents interpretation of the counts as proportions and limits direct comparison across groups.

The analysis details are sparse. The record names a chi-squared test and reports an overall p-value, but does not give the underlying table, the test construction, a confidence interval, or a dose-specific effect estimate. It also does not explain whether and how multiple segments contributed by the same participant were handled. If observations within a participant are related, that dependence can matter for statistical uncertainty; whether it was addressed is not reported in the registry record.

Although the study is labeled randomized and triple-masked, the randomization procedures, masking roles, and implementation details are not reported. The analysis population and participant flow are also not specified. The registry does not explain the handling of missing imaging assessments, technically inadequate segments, or other unevaluable outcomes. The listed participant counts do not by themselves identify the population used for each analysis.

The primary endpoint is assessed by off-site reader 1, and the record does not describe results from other readers or reader agreement. The analysis plan for multiple outcomes and analyses, including any adjustment for multiplicity, is not reported. The sample-size justification and the basis for selecting the planned enrollment are also not reported in the registry record.

These limitations do not demonstrate that the underlying study procedures were inadequate. They identify information unavailable in the registry record, which constrains independent assessment of the effect’s size, precision, and robustness.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Coronary MDCTA With Iopamidol Injection 370 — NCT00558792.
• Registry record last updated 2012-10-24; status last verified 2012-10.
• Results first posted 2012-10-19.
• 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.

19. Record Summary

NCT00558792 is a completed Phase II, randomized, triple-masked, parallel-group study of iopamidol injection 370 in patients with suspected coronary artery stenosis. The registry lists an enrollment of 210, a study start of 2007-11, and primary completion in 2010-05. The sponsor is Bracco Diagnostics, Inc.

The three groups received Isovue 370 at 70 mL, 80 mL, or 90 mL. The primary outcome was the number of coronary artery segments judged adequately visualized for accurate diagnosis by off-site reader 1 immediately post dose. The registry reports group counts of 949, 842, and 841, respectively, and an overall chi-squared p-value of 0.010.

The record also lists a secondary adverse-event outcome and reports zero serious adverse events in each group. It does not report segment denominators, pairwise effect estimates, confidence intervals, or sufficient analysis detail to reconstruct the primary test independently.