Renal Effects of Two Iodinated Contrast Media in Patients at Risk Undergoing Computed Tomography: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Renal Effects of Two Iodinated Contrast Media in Patients at Risk Undergoing Computed Tomography (NCT00209417), a randomized phase 4 study. The primary outcome is Assessment of the Incidence Rate of Contrast Medium-Induced Nephropathy (CIN) Between Iodixanol and Iopamidol in Patients With Impaired Renal Function..

2. Clinical Question

3. Trial Design

This was a Phase 4, randomized, parallel-group trial with triple masking. The two intervention groups received iodixanol 320 mg I/mL or iopamidol 300 mg I/mL. The registry lists an enrollment of 656 and identifies renal insufficiency and diabetes mellitus as conditions relevant to the study. The study concerned intravenous contrast use for computed tomography in patients considered at risk of kidney damage.

The registry record lists a start date of 2005-06, primary completion of 2011-05, and status as terminated. The reason for termination is not reported in the registry record. The record does not report the original sample-size justification, the intended statistical plan, or the trial's original design assumptions. The enrollment figure is not the same as the endpoint denominators in the posted results: the primary outcome groups have denominators of 192 for iodixanol and 207 for iopamidol. The registry record does not explain the difference between the enrollment figure and these endpoint analysis denominators.

The study summary says a standard hydration procedure, based on available guidelines, was to be given to all patients. Serum creatinine was to be measured before contrast administration and up to 7 days afterward. The primary endpoint itself uses the period from baseline up to 3 days after contrast administration. The record also lists overall image quality in contrast-enhanced multidetector-row helical computed tomography as a secondary outcome. One secondary outcome is posted, but the registry record lists no analyses for it.

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

Analysis population for the primary outcome, as defined in the registry: To calculate the incidence rate of CIN, divide the number of subjects affected by the total number of subjects dosed in each treatment group.

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 Assessment of the Incidence Rate of Contrast Medium-Induced Nephropathy (CIN) Between Iodixanol and Iopamidol in Patients With Impaired Renal Function., measured over From baseline up to 3 days post contrast administration..

The primary endpoint is the incidence rate of contrast medium-induced nephropathy (CIN), expressed as a percentage of subjects. CIN was defined as an individual increase in serum creatinine of at least 44.2 µmol/L (at least 0.5 mg/dL) from baseline. The stated timeframe runs from baseline up to 3 days after contrast administration.

The endpoint definition also limits which subjects contribute to the incidence calculation. The registry describes baseline eligibility as serum creatinine of at least 1.5 mg/dL for males or at least 1.3 mg/dL for females, or an estimated glomerular filtration rate of at most 50 mL/min/1.73m squared. A post-contrast serum creatinine measurement on day 2 or day 3 was required, as was administration of at least 100 mL or at least 1.5 mL/kg bodyweight of the study medication. Subjects with major protocol violations or evidence of other causes of acute renal dysfunction were excluded from the endpoint definition.

Serum creatinine is used as a measurable indicator of change in kidney function after contrast administration. The registry summary describes measurements before contrast and up to 7 days afterward, while the primary outcome window is up to 3 days. The endpoint is a specified laboratory threshold, not a measure of every possible kidney outcome or of longer-term kidney function.

7. Results Posted in the Registry

• Iopamidol 300-Arm 2: 10.6% (22/207) versus 9.9% (19/192) on control; risk difference 0.7 percentage points (95% CI -5.2 to 6.7), risk ratio 1.07 (0.60–1.92); unadjusted two-proportion z-test p = 0.810.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each subject either met the specified CIN definition or did not. The group result is expressed as a percentage of subjects with the event. The registry defines the event using a rise in serum creatinine from baseline and specifies the eligible subjects and measurement window. This matters because a percentage is meaningful only in relation to the population and event definition used to calculate it.

What does the risk difference represent?

A risk difference compares the event proportions in two groups by subtracting one group's proportion from the other's. It is an absolute measure: its scale is the change in the proportion experiencing the event, rather than a ratio of the groups. In the posted comparison, the risk difference is 0.007 for iopamidol relative to iodixanol. Its confidence interval runs from -0.052 to 0.067. The interval includes zero, which corresponds to no difference in the event proportions. It also includes estimates in either direction, so the result does not establish which group had the lower underlying event rate.

The relative measures listed in the registry are a risk ratio of 1.074, with an interval from 0.600 to 1.921, and an odds ratio of 1.083, with an interval from 0.567 to 2.07. A risk ratio compares event probabilities as a ratio; an odds ratio compares event odds as a ratio. Both are relative measures, unlike the absolute risk difference. Their intervals also include the no-association value of one. Each measure answers the comparison on a different scale, and none should be interpreted as a guarantee about an individual participant.

How should the p-value be read?

The unadjusted p-value is 0.81. A p-value describes how compatible the observed data, and results at least as discrepant under the chosen test, are with a null hypothesis. It is not the probability that the treatments are equal, nor the probability that the observed difference arose by chance. Interpretation also depends on the analysis method and assumptions. The registry record does not report the trial's original statistical analysis plan or detailed test specification, so the p-value should be read as the posted unadjusted comparison rather than as evidence of an undocumented analysis procedure.

What does over-dispersion mean in general?

In general, over-dispersion means that observed variation is greater than a statistical model expects. It can make model-based standard errors too small if not accounted for, and can affect confidence intervals and tests. For a binary endpoint, whether over-dispersion is a concern depends on the model and data structure. The registry record does not report an over-dispersion assessment or a model-based analysis for this comparison, so no claim can be made about whether it was evaluated or present.

What can be inferred from the denominators?

The posted endpoint denominators are 192 for iodixanol and 207 for iopamidol, and the posted event counts are 19 and 22. These denominators are tied to the endpoint population definition, which requires specified baseline kidney-function values, post-contrast measurements on days 2 or 3, qualifying dose, and absence of specified exclusions. The registry record's enrollment is 656, but the record does not explain how the enrolled group relates to the endpoint denominators. The counts and rates should therefore be interpreted as the posted endpoint results, not as outcomes observed in every enrolled participant.

How should uncertainty be separated from the point estimate?

A point estimate gives one numerical summary of the observed comparison. A confidence interval gives a range of values compatible with the data under the method used, reflecting sampling uncertainty. It does not mean that a fixed proportion of individual participants have effects inside the interval. Here, the confidence interval for the risk difference is much more informative about uncertainty than the point estimate alone: it spans both negative and positive values. The posted results are therefore not precise enough to settle the direction or magnitude of the group difference.

The arm-level rates and confidence intervals describe each group separately; the risk difference and its interval address the comparison directly. The unadjusted label indicates that the reported comparison does not account for covariates in an adjusted model. Whether the original protocol specified another analysis, or how any other planned analyses were conducted, is not reported in the registry record.

10. Confidence Intervals and Precision

The primary outcome estimates are 9.9% for iodixanol and 10.63% for iopamidol. Their respective 95% confidence intervals are 5.67 to 14.12 and 6.43 to 14.83. The interval for the unadjusted risk difference is -0.052 to 0.067 around an estimate of 0.007. These ranges convey substantial uncertainty around the group rates and the comparison.

A confidence interval gives a range of estimates compatible with the data under the statistical method used. It is not a range containing a known proportion of individual outcomes, and it does not assign a probability to a particular treatment effect. For the risk difference, zero lies within the interval. Thus, the data are compatible with no difference as well as with a difference in either direction. The interval's breadth means the estimate is not highly precise enough to identify the direction and size of the group contrast.

Arm-level intervals describe uncertainty in each rate separately; the risk-difference interval is the direct interval for the comparison. The registry does not report an adjusted confidence interval or enough detail to evaluate alternative methods. The confidence intervals should be interpreted in the context of the endpoint's restricted eligibility criteria and the posted denominators of 192 and 207. They do not characterize outcomes among all 656 enrolled participants or outcomes beyond the stated follow-up window.

11. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm, not total events. The planning illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as a reference and considers planning for 100%, 75%, and 50% of that observed effect. The original trial's design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the stated effect under its assumptions. The 90% power column gives the corresponding planning number for a 90% chance. These are design targets, not outcomes of the trial. In general, a smaller effect is harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants. The listed figures increase as the assumed effect fraction decreases.

The calculation is a planning illustration based on the posted observed effect, not a reconstruction of the trial's original design. It is not observed power. Power is a prospective design property under specified assumptions; it should not be used after the fact as a measure of whether the trial's result is reliable. The registry record does not report whether these particular assumptions were used when the trial was planned.

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

Worked calculation for this trial

1. Control proportion p₀ = 0.099; treatment proportion p₁ = 0.106; average p̄ = 0.103.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4292 = 0.8411.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4291 = 0.3612.
4. n = (0.8411 + 0.3612)² / (0.0073)² = 26,963.8, rounded up to 26,964 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 <- 0.0989583333333333                          # control proportion
p1 <- 0.106280193236715                          # 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(209417)
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 = 26,964 (80% power), 36,097 (90% power)
 75% of observed effect: n per arm = 47,558 (80% power), 63,666 (90% power)
 50% of observed effect: n per arm = 106,151 (80% power), 142,106 (90% power)
power.prop.test: 26963.8 
Simulated power at n = 26,964 per arm: 0.800 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and one secondary outcome, overall image quality. It reports two outcome measures, but no analyses are listed for the secondary outcome. The registry record does not report whether there were additional prespecified analyses, multiple comparisons, or an adjustment for multiplicity. Without that information, the interpretation should remain focused on the posted primary comparison rather than assume that all analyses or outcomes were accounted for in a single statistical plan.

The posted primary comparison is unadjusted. The registry record does not report covariate adjustment, an analysis plan, interim analyses, or a method for handling multiple looks at the data. It also does not report the original sample-size justification. These are reporting gaps; they do not establish that such procedures were or were not used outside the information recorded in the registry.

The endpoint definition requires a post-contrast serum creatinine value on day 2 or day 3 and excludes subjects with major protocol violations or evidence of other causes of acute renal dysfunction. The registry record does not report how missing serum creatinine measurements were handled, how many subjects had missing outcome data, or whether missingness differed between groups. It also does not report an imputation method or sensitivity analysis. Since the primary analysis denominator is smaller than the enrollment figure, the absence of a participant flow and missing-data account limits assessment of how the endpoint population was formed.

The registry record does not provide enough detail to identify the full analysis population beyond the endpoint eligibility criteria, or to determine whether the comparison was based on intention-to-treat, per-protocol, or another analysis set. The interpretation should therefore describe the posted endpoint denominators and avoid assigning an analysis-population label that is not reported.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: pancreatic carcinoma (0.3%), cardiac failure (0.3%), cardiac failure congestive (0.3%), renal failure acute (0.3%), renal impairment (0.3%).

The serious adverse event figures list 6 participants affected among 321 at risk in the iodixanol group and 6 among 327 at risk in the iopamidol group. The other adverse event figures list 0 among 321 and 0 among 327, respectively. These counts are separate from the primary CIN endpoint results and should not be treated as a complete description of all possible safety outcomes.

The registry also lists serious adverse event terms, each with a reported frequency of 0.3%: Pancreatic Carcinoma, Cardiac Failure, Cardiac Failure congestive, Renal failure Acute, Renal Impairment, and Pleural Effusion. The term list does not provide arm-specific frequencies for those terms. Death counts are not reported in the registry record.

These figures describe what is recorded in the registry, not a causal comparison of safety between interventions. The registry record does not report detailed event narratives, timing, severity grading beyond the serious designation, or a statistical comparison of adverse events. The figures should be read alongside their stated denominators and the limits of the available reporting.

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

The posted results show similar observed primary endpoint rates in the two groups: 9.9% for iodixanol and 10.63% for iopamidol. The estimated unadjusted risk difference is 0.007, and its 95% confidence interval ranges from -0.052 to 0.067. Because the interval includes zero and extends in both directions, the comparison does not determine whether the underlying event rate was higher in one group or the other. The p-value of 0.81 likewise does not provide strong statistical evidence against no difference.

This does not prove that the treatments have identical effects. A nonsignificant comparison can reflect a small difference, considerable uncertainty, or both. The confidence interval indicates that the estimate is imprecise and that a range of possible group differences remains compatible with the data. The registry results therefore do not support a definitive claim of equivalence or a definitive claim that one intervention is superior.

The finding applies to the registry-defined CIN endpoint, its eligibility requirements, and the period from baseline up to 3 days after contrast administration. It is not a result about every aspect of kidney function, outcomes over longer follow-up, image quality, or all enrolled subjects. The study summary describes serum creatinine monitoring up to 7 days, but the primary endpoint timeframe is up to 3 days.

The available record also leaves important context unreported, including the original sample-size justification, detailed missing-data handling, analysis populations, and reason for termination. Those gaps constrain conclusions about trial conduct and the intended statistical approach. The posted data are best read as an uncertain estimate for the stated comparison and endpoint, not as medical guidance or a general conclusion about contrast media.

16. Why This Trial Matters Statistically

This trial illustrates the difference between an observed rate and a precise comparative conclusion. The group rates are close in the posted results, but the confidence interval for the risk difference is broad and includes zero. Reporting the interval alongside the estimate makes the uncertainty visible; relying on the point estimate or p-value alone would obscure how much the comparison remains unresolved.

It also highlights why endpoint populations and denominators matter. The registry lists an enrollment of 656, while the primary endpoint denominators are 192 and 207. The endpoint criteria impose specific baseline kidney-function, measurement, dose, and exclusion requirements. Without a participant flow or explanation of the denominator differences, it is difficult to assess how broadly the primary rates represent the enrolled population.

The trial record distinguishes planned monitoring from the primary endpoint window: serum creatinine was to be measured up to 7 days after contrast, while the endpoint is defined through 3 days. That distinction matters when describing what the outcome captures. The record further lists an image-quality secondary outcome but no posted analyses for it, reminding readers that an outcome's presence in a registry does not mean that results are available.

Finally, the planning illustrations should not be mistaken for the trial's original design or for observed power. They show how assumed effect size and target power influence planning requirements under stated assumptions. The trial-specific justification and original design assumptions are not reported in the registry record.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry reports an enrollment of 656 but gives primary endpoint denominators of 192 and 207. It does not explain the relationship between these figures, provide a participant flow, or report how many participants were excluded from the endpoint analysis and for what reasons. The primary endpoint definition itself excludes subjects with specified protocol violations or other causes of acute renal dysfunction and requires a post-contrast measurement on day 2 or day 3, but the record does not detail how these criteria affected the final groups.

The registry record does not report missing-data methods, the number of missing serum creatinine measurements, or sensitivity analyses. It does not identify the analysis population as intention-to-treat, per-protocol, or another set. The comparative result is unadjusted, and no adjusted analysis is reported. The original statistical plan, interim analyses, and sample-size justification are also not reported.

The study status is terminated, but the reason for termination is not reported in the registry record. Although the summary describes serum creatinine measurement up to 7 days, the primary endpoint covers baseline to 3 days; conclusions from the primary outcome are limited to that stated window. The listed secondary outcome concerns overall image quality, but no analyses are posted for it. Safety reporting includes serious adverse event counts and listed terms, but death counts and detailed event descriptions are not reported. These limitations restrict assessment of completeness, analysis choices, and the scope of interpretation.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Renal Effects of Two Iodinated Contrast Media in Patients at Risk Undergoing Computed Tomography — NCT00209417.
• Registry record last updated 2014-10-17; status last verified 2014-10.
• Results first posted 2014-10-10.
• 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

The registry describes a Phase 4, randomized, triple-masked, parallel-group comparison of iodixanol 320 mg I/mL and iopamidol 300 mg I/mL in patients at risk of kidney damage undergoing computed tomography. Enrollment is listed as 656; the study status is terminated, and the reason is not reported in the registry record.

The primary outcome is CIN incidence from baseline up to 3 days after contrast administration, defined by a specified rise in serum creatinine. Posted rates are 9.9% for iodixanol and 10.63% for iopamidol. The unadjusted risk difference is 0.007, with a 95% confidence interval from -0.052 to 0.067 and p = 0.81. The interval includes zero and allows for differences in either direction. The record lists one secondary outcome, overall image quality, without a posted analysis.