Primovist / Eovist in Renally Impaired Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Primovist / Eovist in Renally Impaired Patients (NCT00908596), a na phase 4 study. The primary outcome is Number of Participants With Moderate to Severe Renal Impairment, Who Develop NSF (Nephrogenic Systemic Fibrosis), Based on Diagnostically Specific Clinical and Histopathological Information.

2. Clinical Question

The study addressed a potential safety concern: whether NSF would be identified after administration of a gadolinium-containing contrast agent in patients with renal impairment. Its primary focus was not a comparison of treatment effectiveness. Instead, it sought to count participants meeting a specified case definition after the MRI scan. The record also lists secondary assessments concerning NSF-like symptoms, investigator diagnostic confidence, and MRI ratings for lesion detection, delineation, and characterization.

3. Trial Design

This was a prospective, open-label, multicenter, non-randomized, pharmacoepidemiologic cohort study, classified as Phase 4. The registry record lists the study status as completed and enrollment as 357. The listed study start was 2009-05, and primary completion was 2013-07. Participants were patients with renal impairment scheduled for an MRI scan with Primovist/Eovist. The study description states that participants would be followed for two years after the scan to assess signs or symptoms suggestive of NSF; the primary endpoint timeframe is stated as up to 24 months following administration.

Participants received gadoxetic acid disodium intravenously at 0.025 mmol/kg body weight. The primary outcome population is the Full Analysis Set, defined in the record as all participants who were enrolled and received Primovist/Eovist. The endpoint itself concerns participants with moderate to severe renal impairment. The safety listings are separated into mild, extended moderate, moderate, and severe renal-impairment categories, but these categories do not create a randomized comparison.

Because the study had a single-group model and no random allocation, it can describe observed outcomes among participants who received the contrast agent, subject to the record’s reporting and follow-up. It cannot, on this design alone, establish what would have occurred in a concurrent untreated or alternative-treatment group. The registry record does not report a protocol-level statistical plan, a sample-size justification, or details of interim analyses. The planning illustrations associated with the posted results use an equal-allocation, two-arm assumption; that assumption is not a description of this single-group cohort’s actual design.

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: A total of 364 participants were enrolled. Of these, 4 were withdrawn prior to magnetic resonance imaging (MRI) already since they failed to meet the study entrance criteria, and 3 were withdrawn for other reasons. Participants had to have moderate to severe renal impairment (estimated glomerular filtration rate \[eGFR\] 65 mL/min/1.73 m\^2 or less).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: all participants who were enrolled and received Primovist/Eovist

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 Number of Participants With Moderate to Severe Renal Impairment, Who Develop NSF (Nephrogenic Systemic Fibrosis), Based on Diagnostically Specific Clinical and Histopathological Information, measured over Up to 24 months following the administration of Primovist/Eovist.

The primary endpoint is the number of participants with moderate to severe renal impairment who developed NSF, assessed using diagnostically specific clinical and histopathological information. It is a count endpoint: it records participants classified as meeting the case definition, rather than a continuous measure of symptom severity or a treatment-effect estimate. The stated observation period is up to 24 months following Primovist/Eovist administration.

The registry record defines a combined scoring rule. Clinical and histopathological information are each scored on a scale from 0 to 4, with the categories ranging from other diagnosis through inconsistent, suggestive, consistent, and highly consistent. A diagnosis was assumed when either the clinical score or histopathology score was at least 2 and the other score was at least 3. The rule therefore requires support from both types of information, with the scores meeting the specified thresholds; it is not simply a symptom count.

Such a defined endpoint can make case classification more explicit than an unstructured report of suspected disease. Requiring clinical and histopathological information may help distinguish NSF from other explanations for findings. However, the registry record does not report the primary endpoint count or the score data used to classify participants. It is therefore not possible to describe the observed frequency of cases from the record information available. The endpoint definition explains what would count as an event, not how many events were observed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary count represent?

As a general statistical concept, a count endpoint records how many people meet an event definition. In this study, the event is not defined merely by an isolated symptom or by a broad adverse-event label. The registry record specifies a combined clinical and histopathological classification rule for NSF. Clinical and histopathological information each receive a score on a scale from 0 to 4. The case definition requires either score to be at least 2 and the other to be at least 3. Applying a rule in advance helps make the endpoint’s meaning more concrete, although the registry record does not report the participant-level scores or the resulting primary count.

What can a single-group cohort estimate?

As a general statistical concept, a cohort can describe the frequency of an outcome among the people observed, given an outcome definition and a follow-up period. This study’s primary timeframe is up to 24 months following administration. A cohort count does not by itself separate the effect of an exposure from other influences, because it does not compare outcomes under randomized exposure assignments. Here, the study is explicitly non-randomized and single group. The registry record does not describe a concurrent control group, and the renal-impairment categories in the safety listings should not be interpreted as randomized treatment arms.

In a comparative trial, an effect estimate would usually describe a difference or other contrast between groups. No such primary contrast is defined in the record for this cohort. It would therefore be inappropriate to turn the observed safety-category counts into a treatment-effect estimate or to treat a renal category as a control group. The record’s stated enrollment and endpoint population definition also do not provide a primary-outcome numerator.

How should uncertainty be understood?

As a general concept, a confidence interval describes the statistical uncertainty around an estimate under a specified model and procedure. A narrow interval indicates greater precision than a wide interval, while neither guarantees that the true value is contained in the interval. For a count or event frequency, uncertainty depends on both the observed event information and the method used to calculate the interval. The registry record does not report a primary endpoint estimate or interval, so its precision cannot be assessed from the recorded primary result.

For rare outcomes, limited event information can leave substantial uncertainty even when no cases are observed. This is a general statistical point, not a claim about the primary outcome in this study: the registry record does not state the primary NSF event count. In addition, incomplete follow-up or missing outcome assessments can affect the interpretation of a cohort estimate. The record information does not explain how missing follow-up or unavailable diagnostic information was handled.

What is over-dispersion, and does it apply?

As a general explanation, over-dispersion occurs when outcome variability is greater than assumed by a simple statistical model. It can matter for count outcomes when events cluster or when participants differ in ways that make outcomes less uniform than the model expects. A model that ignores over-dispersion may give uncertainty estimates that are too small. The registry record does not report a count model, a dispersion estimate, or a model-based primary analysis. There is therefore no basis to say that over-dispersion was assessed or that a particular model was used.

How do the planning illustrations relate to this design?

The sample-size assumptions describe planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event illustrations, the stated quantity is a total number of events; for other illustrations, it is participants per arm. These are hypothetical planning calculations, not observed power, not observed outcomes, and not a description of the recorded cohort’s allocation. In particular, the equal-allocation, two-arm assumption does not match the single-group design described in the registry record. The record does not report the original study’s sample-size justification or its statistical analysis plan.

As a general matter, a planning calculation depends on the assumed effect, significance level, allocation, outcome model, and desired power. A calculation based on an observed effect can be useful as an illustration of what a future design might require under stated assumptions, but it does not show that the completed study had that power. The record does not provide enough information to assess the suitability of the original enrollment target for the primary endpoint.

What can be concluded from the posted analyses?

The registry record lists no analysis records. It does provide the endpoint definition and the descriptive adverse-event counts, but it does not provide a numerical primary endpoint result, a primary statistical test, or an interval estimate. No unreported analysis method should be inferred. The distinction is important: a definition describes what investigators intended to count, while an analysis result reports what was observed and how uncertain that observation is.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Gadoxetic Acid Disodium - Mild Renal Impairment", "Gadoxetic Acid Disodium - Extended Moderate Renal ", "Gadoxetic Acid Disodium - Moderate Renal Impairmen", "Gadoxetic Acid Disodium - Severe Renal Impairment")
n      <- c(47, 32, 193, 85)
events <- c(0, 0, 0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Gadoxetic Acid Disodium - Mild Renal Impairment  47  0  0.0  0.0  7.5  0.0  7.6  0.1  7.4
ARM  Gadoxetic Acid Disodium - Extended Moderate Renal   32  0  0.0  0.0  10.9  0.0  10.7  0.1  10.6
ARM  Gadoxetic Acid Disodium - Moderate Renal Impairmen  193  0  0.0  0.0  1.9  0.0  2.0  0.0  1.9
ARM  Gadoxetic Acid Disodium - Severe Renal Impairment  85  0  0.0  0.0  4.2  0.0  4.3  0.0  4.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and several secondary outcomes. These include NSF-like symptoms among participants without a biopsy, investigator confidence in diagnosis based on the enhanced MRI, and ratings for lesion detection, lesion delineation, and lesion characterization. Having multiple outcomes can raise a multiplicity issue: as a general statistical concept, testing several hypotheses can increase the chance of at least one apparently unusual result if no adjustment or hierarchy is used. The record information does not describe a multiplicity adjustment, a testing hierarchy, or which secondary outcomes were intended to support confirmatory conclusions.

The registry record lists no analysis records and does not report the numerical primary outcome. It also does not state how missing outcome assessments, incomplete follow-up, unavailable biopsies, or participants not assessed through the full follow-up period were handled. The secondary outcome concerning participants in whom no biopsy was obtained indicates that biopsy availability was relevant to at least one planned assessment, but the record does not provide the analysis rules or counts needed to characterize its impact.

The primary endpoint population is defined as all participants who were enrolled and received Primovist/Eovist. That definition identifies the stated Full Analysis Set, but it does not explain whether every participant in that set had complete follow-up or usable clinical and histopathological information. The record does not report the number included in the primary analysis, the number with missing endpoint data, or any imputation or sensitivity-analysis approach. Those details are not reported in the registry record, so the potential influence of missing information on the primary estimate cannot be evaluated.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: basal cell carcinoma (1.2%).

The registry safety listings separate participants by renal-impairment category and distinguish serious from other adverse events. Serious adverse events are listed for 0 of 47 participants with mild impairment, 0 of 32 with extended moderate impairment, 0 of 193 with moderate impairment, and 1 of 85 with severe impairment. Other adverse events are listed for 0 of 47, 1 of 32, 7 of 193, and 6 of 85, in the same category order. These are descriptive counts in the registry record; they are not a randomized comparison and should not be interpreted as evidence that one category has a higher or lower risk than another.

The record lists basal cell carcinoma at 1.2% among the top serious terms. It does not specify in the information the denominator or category associated with that term, so that percentage should be retained as reported without assigning it to a particular group. Death counts are not reported in the record information. An unreported death count must not be read as evidence that no deaths occurred.

These safety listings are distinct from the primary NSF endpoint. The primary endpoint uses the specified combined clinical and histopathological score rule; a general adverse-event count does not show whether that rule was met. The numerical primary NSF result is not reported in the registry record.

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

The study record describes a prospective effort to assess NSF after Primovist/Eovist administration among patients with renal impairment. It specifies a follow-up timeframe of up to 24 months and a case definition based on both clinical and histopathological information. It also reports adverse-event counts by renal-impairment category. These details explain what was studied and how the primary outcome was intended to be classified.

The record does not report the number of participants who met the primary NSF definition. It therefore does not support a numerical statement about the observed primary outcome, its frequency, or the precision of that estimate. The adverse-event counts cannot fill this gap because they refer to separate safety listings and do not establish which participants met the NSF case definition. A missing primary result should not be interpreted as a zero-event finding.

Even if a primary count were available, this non-randomized, single-group design would principally describe outcomes in the observed cohort. Without a concurrent comparison group, it would not establish how outcomes would have differed under another contrast agent or without contrast administration. The record also does not report the details needed to assess whether follow-up or outcome ascertainment was complete.

The planning illustrations are not observed power and are based on a two-arm equal-allocation assumption that does not match the study design. They cannot be used to claim that the cohort had a particular probability of detecting an effect. The record’s results should therefore be read narrowly: it supplies study-design details and some descriptive safety counts, but not a numerical primary outcome or comparative estimate. It does not, on its own, establish a causal treatment effect or resolve the potential risk posed in the study question.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary outcome concerns a clinically specific event assessed through a combined diagnostic rule rather than a broad symptom label. The requirement that clinical and histopathological scores meet complementary thresholds makes the endpoint definition explicit. That can support consistent classification in principle, but interpreting the findings requires the observed count and information about how diagnostic data were obtained and handled. The registry record does not report the primary count or the analysis details needed to evaluate those elements.

The single-group cohort design also matters. It is suited to describing outcomes observed after exposure in the enrolled population, but it does not provide a randomized counterfactual. The listed renal categories are useful for organizing descriptive safety information, yet they are not interchangeable with randomized comparison groups. Statistical interpretation must keep descriptive counts separate from claims about causal differences.

The record further illustrates why outcome reporting and uncertainty matter when the study question concerns a rare condition. A clearly defined endpoint is only one part of an interpretable result; readers also need the observed number of cases, the population assessed, follow-up completeness, and an uncertainty estimate or other account of precision. Those primary-result details are not reported in the registry record. The adverse-event counts provide some safety information but cannot answer the primary endpoint question.

Finally, the planning illustrations use equal allocation between two arms, whereas the study is recorded as a single-group cohort. Keeping design assumptions separate from the actual study avoids treating hypothetical sample-size calculations as evidence about observed power or as a description of the trial’s original plan.

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 principal limitation for interpreting the registry record is that the numerical primary outcome is not reported. Although the endpoint definition and timeframe are described, the number of participants meeting the NSF criteria and the precision of that result are unavailable. The posted adverse-event counts do not replace the missing primary endpoint result.

The study is non-randomized and has a single-group model, with no concurrent control group described. This limits causal interpretation: observed outcomes in the cohort cannot by themselves show what would have happened under a different contrast agent or without contrast. The renal-impairment categories in the safety listings are descriptive categories, not randomized comparators.

The record information does not report completion of follow-up, the number of participants with complete endpoint assessments, how unavailable histopathological information was handled, or how missing data were addressed. Although the study description states a two-year follow-up and the primary timeframe is up to 24 months, the record does not provide enough information to assess completeness of observation for the primary outcome.

The statistical analysis plan, sample-size justification, interim analyses, and multiplicity procedures are not reported in the registry record. The planning illustrations use a two-arm equal-allocation assumption that differs from the recorded single-group design and should not be treated as the original study plan or as observed power. Finally, the safety counts are descriptive and do not establish whether the primary NSF classification criteria were met.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Primovist / Eovist in Renally Impaired Patients — NCT00908596.
• Registry record last updated 2015-07-23; status last verified 2015-07.
• Results first posted 2014-08-07.
• 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

The registry record describes a completed Phase 4, prospective, open-label, multicenter, non-randomized, single-group cohort study of Primovist/Eovist in patients with renal impairment. Listed enrollment is 357. Participants received gadoxetic acid disodium at 0.025 mmol/kg body weight intravenously. The primary outcome is the number of participants with moderate to severe renal impairment classified as developing NSF using combined clinical and histopathological scoring, with follow-up up to 24 months.

The record lists secondary assessments of NSF-like symptoms, investigator diagnostic confidence, and MRI lesion ratings. It also reports serious and other adverse-event counts by renal-impairment category. The numerical primary NSF result, its uncertainty, and details of missing-data handling and the statistical analysis plan are not reported in the registry record.