Performance of Elucirem in DSC-MRI Perfusion of Brain Gliomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Performance of Elucirem in DSC-MRI Perfusion of Brain Gliomas (NCT06057168), a randomized phase 3 study. The primary outcome is Diagnostic Quality of Cerebral Blood Volume (CBV) Map of Dynamic Susceptibility Contrast MRI (DSC-MRI) Perfusion.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group Phase IIIb trial comparing Elucirem with Dotarem for DSC-MRI perfusion of brain gliomas. The registry lists the trial phase as Phase 3 and describes it as a Phase IIIb clinical trial. It records a single-masked design, but which participants or study personnel were masked is not reported in the registry record. The allocation ratio is not specified in the registry record.

The trial enrolled 138 participants and is listed as completed. The recorded study start date is 2023-09-07, and the primary completion date is 2024-11-28. Participants in one group underwent DSC-MRI perfusion using Elucirem, while participants in the other group underwent the procedure using Dotarem. The primary endpoint was assessed during the MRI procedure, from its beginning to its end.

The primary analysis was per protocol. It included 124 participants with a diagnostic CBV map and without a major protocol deviation: 60 in the Elucirem group and 64 in the Dotarem group. The overall enrollment and the per-protocol analysis population are different populations; the registry does not explain the disposition of every enrolled participant. The safety counts are reported for 67 participants in the Elucirem group and 69 in the Dotarem group.

Randomization and masking can help reduce some sources of bias, but the registry record does not describe the randomization procedure, concealment of allocation, or who was masked. It also does not report the trial's original sample-size assumptions or a detailed statistical analysis plan. The record therefore supports a description of the design features and posted analyses, but not a fuller reconstruction of how the trial was planned or conducted.

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: Out of the 141 screened patients, 3 patients were screen failed. Therefore, 138 patients were randomized in the trial with 69 in each arm. Out of them, 2 patients prematurely discontinued the study before the injection of contrast agent. The remaining 136 patients underwent MRI examination with injection of IMP: 67 with Elucirem and 69 with Dotarem. A total of 124 patients were included in the per-protocol primary analysis: 60 with Elucirem and 64 with Dotarem.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-protocol analysis included 124 patients (60 with Elucirem and 64 with Dotarem) with diagnostic CBV map and without protocol major deviation evaluated by two independent off-site readers.

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.

Population: Baseline description for safety population (patients received an injection of contrast agent): A total of 136 patients including 67 patients who received an injection of Elucirem and 69 patients who received an injection of Dotarem.

6. Primary Endpoint

The registry lists the primary outcome as Diagnostic Quality of Cerebral Blood Volume (CBV) Map of Dynamic Susceptibility Contrast MRI (DSC-MRI) Perfusion, measured over From beginning to end of procedure for DSC-MRI perfusion using Elucirem or Dotarem.

The primary endpoint was diagnostic quality of the CBV map obtained from DSC-MRI perfusion. Two off-site blinded readers assessed each participant's map using four categories: poor, fair, good, or excellent. When the two readers disagreed, a consensus assessment was used. The primary comparison concerned the proportion of participants with an image rated good or excellent.

This endpoint captures whether the resulting image was considered suitable in diagnostic-quality terms by the readers. Combining good and excellent ratings defines the success category used for the primary comparison, while fair and poor ratings fall outside that category. The outcome is reported as participants, so the observed data are counts of participants meeting that image-quality definition, rather than a continuous measure of image characteristics.

Reader assessment is relevant to an imaging-agent comparison because the study question concerns the quality of the images acquired using each agent. Blinded off-site reading is intended to limit the influence of knowledge about group assignment on those assessments. Consensus in the event of disagreement provides a final classification for the primary outcome, although the registry does not report how often disagreements occurred or how consensus was reached.

The endpoint is specific to image quality during the MRI procedure. It does not directly measure diagnostic accuracy, changes in clinical decisions, tumor outcomes, or patient health. Those outcomes are not reported as secondary posted outcomes in the registry record.

7. Results Posted in the Registry

• Dotarem: 98.4% (63/64) versus 96.7% (58/60) on control; risk difference 1.8 percentage points (95% CI -3.7 to 7.2), risk ratio 1.02 (0.96–1.08); unadjusted two-proportion z-test p = 0.521.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either had a CBV map rated good or excellent, or did not. The registry reports the number meeting the good-or-excellent definition in each group. A comparison of the proportions is therefore a natural way to describe the observed group difference. The analysis population is per protocol, meaning the primary analysis excludes participants outside the stated criteria of having a diagnostic CBV map and no major protocol deviation. The registry does not give the full set of protocol deviations or explain all exclusions.

What does a risk difference describe?

A risk difference subtracts one group's event proportion from the other group's event proportion. In the recalculation, the direction is Dotarem relative to Elucirem: the recorded proportions are 0.984 and 0.967, respectively, and the risk difference is 0.018. A positive value in this direction indicates a higher observed good-or-excellent proportion in the Dotarem group. The risk difference is expressed on the proportion scale, which makes it possible to understand the absolute size of the observed contrast without converting it into a relative measure.

The recalculated confidence interval for this risk difference runs from -0.037 to 0.072. Its lower end permits a negative difference, while its upper end permits a positive difference. Since zero is within the interval, the data do not establish a nonzero difference using this interval. That does not prove equivalence: an equivalence conclusion would require a prespecified equivalence range and an analysis designed to assess it. Neither is reported in the registry record.

How does noninferiority differ from a difference test?

A noninferiority analysis asks whether the result for one group is not worse than the comparator by more than a prespecified margin. The margin defines how much disadvantage is acceptable for the trial's question. A confidence interval is interpreted relative to that margin, with its direction depending on how the contrast is defined. The registry reports a two-sided 95% confidence interval of -0.018 to 0.053 for its noninferiority analysis, but the margin and the analysis method are not reported in the registry record. Without the margin, the interval alone cannot establish whether the stated noninferiority criterion was satisfied.

A conventional difference test and a noninferiority analysis answer different questions. The recalculated p-value of 0.521 relates to an unadjusted comparison of the observed proportions; it does not substitute for a noninferiority decision. In particular, a nonsignificant difference test cannot be treated as proof that the groups are sufficiently similar for a noninferiority claim. The sponsor-reported analysis should therefore be read as the registry's stated noninferiority analysis, while the recalculation is a separate descriptive and inferential check based on the posted counts.

Why are confidence intervals useful?

A confidence interval communicates uncertainty about an estimated effect. It gives a range of values compatible with the data and the statistical method used, rather than presenting the point estimate as if it were exact. The interval's width reflects precision: wider intervals indicate that a broader range of effects remains plausible. General statistical interpretation also depends on the analysis assumptions and the population being analyzed. The registry does not report the method used to construct its noninferiority interval, so its precise assumptions cannot be evaluated from the record.

For a binary endpoint, methods can differ in how they estimate the interval, particularly when proportions are near the limits of their possible range. The recalculation is explicitly unadjusted and uses the posted summary counts. It should not be mistaken for an adjusted analysis or for a replacement for a prespecified trial analysis. The registry's reported noninferiority interval is another result and is not reproduced by simply interpreting the recalculated interval.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability is greater than a model assumes. It matters in analyses whose standard errors depend on a variance model, because underestimated variability can make confidence intervals too narrow and tests too optimistic. This primary endpoint is a participant-level binary outcome, and the registry does not report an over-dispersion adjustment or other variance correction. The issue is therefore a general statistical consideration, not a reported feature of this trial's analysis.

What remains unspecified?

The registry record does not report the statistical model or procedure used for the sponsor's noninferiority analysis, the margin, handling of missing endpoint data, or adjustment for other analyses. It also does not report an interim analysis plan. These details matter for interpreting a confirmatory analysis and its uncertainty. The registry entries available support interpretation of the posted counts and intervals, but they do not permit a full audit of the original statistical plan.

10. Confidence Intervals and Precision

The recalculated risk difference for Dotarem relative to Elucirem is 0.018, with a 95% confidence interval from -0.037 to 0.072. This interval includes zero. In practical statistical terms, the observed data are compatible with a range of differences that includes a modest difference in either direction. The point estimate alone does not convey that uncertainty.

The interval is not especially narrow relative to the small observed difference. Its width reflects that the analysis does not identify a single precise value for the underlying group contrast. The p-value of 0.521 is consistent with the interval including zero, but neither statistic demonstrates that the groups are equivalent. A conclusion about noninferiority requires comparing the relevant interval boundary with a prespecified noninferiority margin, which is not reported in the registry record.

The registry's own noninferiority result is a two-sided 95% confidence interval from -0.018 to 0.053. It is separate from the recalculated interval and is reported without the method or margin needed to interpret the decision fully. The two intervals should not be merged or treated as estimates from the same calculation.

Confidence intervals describe uncertainty under the method used; they do not account automatically for every possible source of bias or uncertainty. The per-protocol population, reader assessment process, handling of missing data, and analysis choices can all affect interpretation. Some of these details are not reported in the registry record. Thus, the intervals provide statistical precision for their respective analyses, not a guarantee that the result applies to every population or imaging setting.

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 sample-size table and curve are planning illustrations based on fractions of the observed effect, not the trial's original design calculations. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrations consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect.

For this binary outcome, the figures are participants per arm, not total events. The columns for 80% and 90% power indicate the number of participants per arm estimated to give the analysis an 80% or 90% chance of detecting the specified effect under the stated assumptions, if that effect were the true one. The listed figures are 1,195 and 1,599 participants per arm when planning for 100% of the observed effect; 2,311 and 3,094 when planning for 75% of the observed effect; and 5,620 and 7,523 when planning for 50% of the observed effect.

Smaller effects are harder to distinguish from random variation, so planning to detect a smaller fraction of the observed effect requires more participants per arm. The curve illustrates this relationship across the planning scenarios. These estimates depend on the assumptions stated for the illustration and are not the trial's original sample-size justification, which is not reported in the registry record. This is not observed power; it is a planning calculation based on the observed effect.

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 = 0.967; treatment proportion p₁ = 0.984; average p̄ = 0.976.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.2185 = 0.4283.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.2182 = 0.1836.
4. n = (0.4283 + 0.1836)² / (0.0177)² = 1,194.2, rounded up to 1,195 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 <- 0.966666666666667                          # control proportion
p1 <- 0.984375                          # 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(6057168)
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 = 1,195 (80% power), 1,599 (90% power)
 75% of observed effect: n per arm = 2,311 (80% power), 3,094 (90% power)
 50% of observed effect: n per arm = 5,620 (80% power), 7,523 (90% power)
power.prop.test: 1194.2 
Simulated power at n = 1,195 per arm: 0.808 (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. Analyses Reported by the Sponsor

The registry reports the sponsor's analysis as a noninferiority analysis with a two-sided 95% confidence interval from -0.018 to 0.053. The method, p-value, and noninferiority margin are not reported in the registry record. The interval is therefore the main posted result for that analysis, but the missing margin prevents a complete assessment of the noninferiority criterion.

A separate recalculation from the posted counts gives a risk difference of 0.018 for Dotarem relative to Elucirem, with a 95% confidence interval from -0.037 to 0.072 and p = 0.521. This is an unadjusted calculation based on the per-protocol counts. Its estimate and confidence limits differ from the registry's reported noninferiority interval. The registry record does not explain the analysis choices or estimands that account for that difference, so the results should not be treated as interchangeable.

The sponsor-reported analysis is the trial's posted analysis; the recalculation is an additional summary based on the counts. The discrepancy flag is false, but the difference between these two sets of results remains relevant when interpreting what each analysis represents. Neither interval, without the noninferiority margin and further method details, independently establishes whether the trial met its prespecified noninferiority criterion.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and one reported analysis. It lists no secondary outcomes as posted. The record does not report whether multiple hypotheses, endpoints, readers, or analysis populations were considered in the original statistical plan, or whether any multiplicity adjustment was planned or used. Without that information, the effect of potential multiple testing on interpretation cannot be assessed.

The primary analysis population was per protocol and included 124 participants with diagnostic CBV maps and no major protocol deviation. The registry does not describe the full analysis populations used for other purposes, provide a participant flow accounting for the difference between total enrollment and the primary population, or explain the reasons participants were not included in the primary analysis. Safety counts are separately reported for 67 participants in the Elucirem group and 69 in the Dotarem group.

Missing endpoint data and their handling are not reported in the registry record. It is not possible to tell from the posted information whether missing assessments occurred, how they were treated, or whether sensitivity analyses were performed. This is important for a per-protocol result because exclusions and unavailable assessments can affect which participants contribute to the estimate. The record also does not report whether the main analysis was supported by an intention-to-treat analysis.

The noninferiority margin, the statistical method for the sponsor's analysis, and the original analysis plan are not reported. These details are important because noninferiority interpretation depends on a prespecified margin and a defined analysis approach. Interim analyses and stopping rules are also not reported in the registry record. Their absence from the record should not be interpreted as evidence that such procedures were or were not part of the trial; the posted information does not resolve that question.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 67 participants at risk in the Elucirem group and 69 in the Dotarem group. There were 0 serious adverse events reported in each group. The record also reports 0 deaths in each group.

For other adverse events, the registry reports 3 affected participants among 67 at risk in the Elucirem group and 2 affected participants among 69 at risk in the Dotarem group. These are participant counts, not a measure of event severity or duration. The registry does not list any top serious adverse event terms.

Safety counts should be read separately from the per-protocol primary outcome population. The adverse-event denominators are the safety populations reported in the registry, while the primary analysis used 60 participants in the Elucirem group and 64 in the Dotarem group. The record does not provide further detail about event definitions, collection methods, or the timing of other adverse events. The reported counts describe events recorded in this trial and do not establish comparative safety beyond the information posted.

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

The posted primary counts show that good-or-excellent diagnostic quality was recorded for 58 of 60 analyzed participants in the Elucirem group and 63 of 64 in the Dotarem group. The recalculated proportions are 0.967 and 0.984, respectively. The risk difference and its confidence interval show uncertainty around the observed contrast, with the interval including zero. The point estimate should not be read as a definitive advantage for either group.

The registry's posted noninferiority interval is a distinct analysis. Because the noninferiority margin and method are not reported in the registry record, the information available does not allow a complete check of whether a prespecified noninferiority criterion was met. The recalculated interval cannot stand in for that analysis: it is an unadjusted calculation from the summary counts and answers a different inferential question.

The result concerns reader-rated CBV map quality during DSC-MRI perfusion. It does not establish that either agent improves diagnosis, changes treatment decisions, or affects clinical outcomes. No secondary outcomes are posted in the registry record. Nor can the result automatically be generalized to participants or imaging settings beyond those represented in this trial.

Randomization and blinded reading are relevant design features, but important details remain unreported, including the masking roles, analysis plan, missing-data handling, and noninferiority margin. Those gaps limit how completely the posted result can be evaluated. The most defensible reading is therefore descriptive: the observed good-or-excellent counts were high in both per-protocol groups, and the posted estimates retain uncertainty that cannot be fully interpreted as a noninferiority decision without the omitted design details.

17. Why This Trial Matters Statistically

This trial illustrates why the question behind an analysis matters as much as the point estimate. A comparison of proportions asks about the size and direction of a group difference. A noninferiority analysis asks whether a difference is small enough, relative to a prespecified margin, to satisfy a particular criterion. Those are not interchangeable questions. The registry posts both a noninferiority interval and counts from which an unadjusted comparison can be recalculated, but the margin and sponsor analysis method are not reported.

The example also highlights the value of reading confidence intervals alongside observed counts. The groups had high observed proportions of good-or-excellent image ratings, yet an estimate alone does not tell how precisely the underlying contrast is known. The recalculated interval spans values on both sides of zero, so it does not establish a difference or equivalence. The noninferiority interval likewise cannot be judged against its intended threshold without the margin.

Finally, the endpoint is a reader-rated imaging measure rather than a patient-centered outcome. Understanding exactly what the outcome represents prevents claims from extending beyond the evidence. The trial's design and endpoint are relevant to assessing image quality, while conclusions about diagnostic performance or patient outcomes would require results that are not reported in the registry record.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting noninferiority is that the registry does not report the noninferiority margin. The sponsor-reported interval therefore cannot be compared with the trial's decision threshold using the posted information. The analysis method and p-value are also not reported, limiting assessment of how that interval was obtained. The separate unadjusted recalculation is based on summary counts and should not be mistaken for the prespecified trial analysis.

The primary analysis was per protocol, with 124 participants included from an overall enrollment of 138. The registry does not provide a complete account of participant disposition or explain all reasons for exclusion from the primary population. Missing endpoint data and their handling are not reported. The record also does not state whether an intention-to-treat analysis or sensitivity analyses were conducted.

The outcome depends on reader ratings of CBV maps. Although two off-site blinded readers were used and consensus was specified for discordant ratings, the registry does not report reader agreement, the frequency of disagreement, or how consensus was reached. The record also does not identify who was masked under the single-masked design.

Only one primary outcome measure and one analysis are listed, and no secondary outcomes are posted. Details about multiplicity, interim analyses, and the original sample-size justification are not reported in the registry record. These gaps limit assessment of the planned statistical framework and the completeness of reported outcomes. The results also address image quality during the procedure, not downstream diagnostic or clinical outcomes.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Performance of Elucirem in DSC-MRI Perfusion of Brain Gliomas — NCT06057168.
• Registry record last updated 2026-01-29; status last verified 2025-11.
• Results first posted 2026-01-29.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT06057168 is a completed randomized, parallel-group Phase IIIb trial of Elucirem and Dotarem for DSC-MRI perfusion of brain gliomas. The registry lists a single-masked design and an overall enrollment of 138. The primary endpoint assessed the proportion of participants whose CBV map was rated good or excellent by two off-site blinded readers, with consensus used when ratings disagreed.

The per-protocol primary analysis included 60 participants in the Elucirem group and 64 in the Dotarem group. The reported counts meeting the image-quality criterion were 58 and 63, respectively. The registry posts a noninferiority confidence interval from -0.018 to 0.053; the margin and analysis method are not reported. A separate unadjusted recalculation gives a risk difference of 0.018, with a 95% confidence interval from -0.037 to 0.072.

Safety reporting lists 0 serious adverse events and 0 deaths in each group. Other adverse events affected 3 participants in the Elucirem group and 2 in the Dotarem group.