This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Diagnostic Efficacy of Mangoral in Participants With Focal Liver Lesions and Reduced Kidney Function (NCT04119843), a na phase 3 study. The primary outcome is Co-primary Endpoint: Lesion Border Delineation in Combined MRI Compared to Unenhanced MRI.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04119843 |
| Phase | Phase 3 |
| Condition | Known or Suspected Focal Liver Lesions, Severe Renal Impairment |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 87 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ascelia Pharma AB |
| Results posted | Yes |
2. Clinical Question
Population
Participants with known or suspected focal liver lesions and severe renal impairment. The registry record reports an enrollment of 87 participants.
Intervention
Participants received a single dose of Mangoral, described as 800 mg Manganese (II) chloride tetrahydrate.
Comparator
Unenhanced liver MRI was compared with combined MRI, defined as Mangoral-enhanced MRI combined with unenhanced MRI. This is a comparison of imaging methods within a single-group study, not a randomized comparison of treatment groups.
Primary question
Did combined MRI provide better visualization of focal liver lesions than unenhanced MRI, as assessed by lesion border delineation and lesion contrast?
The study addresses an imaging question in participants who have both focal liver lesions and severe renal impairment. Its co-primary variables concern how clearly lesions can be distinguished from the surrounding liver: lesion border delineation and lesion contrast. The registry describes the assessment as a qualitative rating of detected lesions, with central reading sessions performed by independent, blinded readers.
The comparison is not between Mangoral and a placebo or between separately assigned participant groups. Rather, it concerns MRI methods in the same study population, with combined MRI incorporating both Mangoral-enhanced and unenhanced images. The record specifies unenhanced imaging during the baseline period and combined imaging during the baseline period and 4 hours after Mangoral administration on Day 0.
The central question is therefore about the relative diagnostic appearance of lesions on the imaging methods, not about a clinical treatment outcome. The registry record does not report the co-primary endpoint estimates or their uncertainty, so the direction and precision of the observed efficacy comparison cannot be described from the posted results.
3. Trial Design
This was a Phase 3, multicenter, open-label, single-group study. The registry record lists 87 participants as enrolled and the study status as completed. The study started on 2020-02-19, with primary completion on 2023-02-17.
All participants received a single dose of Mangoral. The record gives the dose as 800 mg Manganese (II) chloride tetrahydrate. It does not describe a separately assigned control group: allocation is listed as not applicable, and masking is listed as none. The diagnostic comparison instead concerns unenhanced MRI and combined MRI, which includes Mangoral-enhanced and unenhanced images.
Open-label describes the study-level masking arrangement recorded in the registry. Separately, the endpoint description says that central reading sessions were conducted by 3 independent, blinded readers. Thus the record distinguishes the study's open-label design from the blinding of the central image readers. It does not report further details about how reader blinding was maintained.
The primary efficacy population is described as the Full Analysis Set. The definition begins with participants in the Safety Population who received the investigational product and whose primary efficacy variable was assessable, including assessable unenhanced and enhanced liver MRI images. The remainder of the population description is incomplete in the registry record, and the number included in this analysis is not reported in the registry record.
The registry record does not report a randomized allocation, a parallel control arm, or a statistical analysis plan. It also does not report the sample-size justification for the clinical trial. Any planning illustrations based on observed effects should be distinguished from the actual design and enrollment of this single-group study.
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: The study consisted of: * Screening Period (Day -28 to Day -1) * Baseline Period (Day -1 to Day 0, i.e., within 24 hours of mangoral administration) providing a Baseline magnetic resonance imaging (MRI) using an unenhanced MRI examination of the liver * Day of MRI (Day 0) included intake of mangoral after a fast of at least 4 hours and a mangoral-enhanced liver MRI 4 \[±1\] hours after mangoral administration * Follow-up visits following contrast administration (up to Day 7).
Overall Study
| Stage | Mangoral |
|---|---|
| STARTED | 87 |
| Underwent Unenhanced MRI | 85 |
| Underwent Mangoral-enhanced MRI | 85 |
| COMPLETED | 83 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Mangoral |
|---|---|
| Adverse Event | 3 |
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): All participants of the Safety Population who received the IMP and for whom the primary efficacy variable was assessable, i.e. all unenhanced / enhanced liver MRI images are assessable. The overall number of participants analyzed includes all participants that contributed data for the outcome measure. The number of participants analyzed per row includes only participants with matched lesions (detected and scored on both unenhanced MRI and combined MRI) by each reader.
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: Safety Population: All participants enrolled in the study (fulfil all inclusion criteria, but none of the exclusion criteria and have been included in the clinical study at Visit 2).
| Characteristic | Unit | Mangoral |
|---|---|---|
| Participants analysed | 87 | |
| Age, Continuous | years | 64.7 (SD 11.63) |
| Sex: Female, Male: Female | Participants | 36 |
| Sex: Female, Male: Male | Participants | 51 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 11 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 28 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 48 |
| Race/Ethnicity, Customized: White | Participants | 28 |
| Race/Ethnicity, Customized: Black or African American | Participants | 5 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 1 |
| Race/Ethnicity, Customized: Other | Participants | 6 |
| Race/Ethnicity, Customized: Unknown or Not Reported | Participants | 47 |
6. Primary Endpoint
The registry lists the primary outcome as Co-primary Endpoint: Lesion Border Delineation in Combined MRI Compared to Unenhanced MRI, measured over Unenhanced MRI: Baseline Period (Day -1 to Day 0); combined MRI: Baseline Period (Day -1 to Day 0) and 4 hours after mangoral administration on Day 0.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The co-primary endpoint includes lesion border delineation and lesion contrast in combined MRI compared with unenhanced MRI. The detailed description defines lesion border delineation as a qualitative assessment of how distinct the lesion border is from the liver background. A score of 1 corresponds to a poorly distinct border, while a score of 4 corresponds to a sharply and clearly distinct border.
Up to 15 lesions per participant could be assessed. The individual lesion scores were summed and averaged for each participant, producing a participant-level score from 1 to 4. Higher scores represent better lesion border delineation. The stated unit is a score on a scale, and the measure is summarized as a mean with standard deviation.
Using a participant-level summary gives each participant a score derived from the lesions assessed for that person, rather than treating every lesion as an independent participant. In general, this can help align the analysis unit with the enrolled participant, although the registry record does not report the full analysis details or how any incomplete lesion assessments were handled.
The endpoint is used to assess image appearance and lesion visualization, rather than a clinical event or health outcome. The record describes central reading by 3 independent, blinded readers. It does not report the primary endpoint means, standard deviations, comparison estimate, confidence interval, or significance test. The detailed scale description is for lesion border delineation; further scoring details for lesion contrast are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted results describe the trial design and endpoint definitions, but they do not report numerical efficacy results for the co-primary variables. In particular, the registry record does not report the average lesion border delineation scores for either imaging method, the comparison between methods, or a measure of uncertainty around that comparison. It also does not report the corresponding lesion contrast results. Consequently, the size, direction, and precision of the diagnostic difference cannot be interpreted from the registry record.
The endpoint scale has a clear stated direction: higher lesion border delineation scores indicate better distinction of the lesion border. That direction helps explain what an estimate would mean, but it does not establish whether scores were higher with combined MRI. Without the observed scores and comparison estimate, it is not possible to state whether the posted efficacy data favor one imaging method or how consistently the scores differed.
The trial compares imaging methods within a single-group study. This is different from a randomized comparison between independently assigned groups. The record describes unenhanced MRI and combined MRI, with the latter incorporating Mangoral-enhanced and unenhanced images. The images are also associated with specified assessment times: unenhanced MRI during the baseline period and combined MRI during the baseline period and 4 hours after Mangoral administration on Day 0. The registry does not provide the numerical results needed to evaluate those assessments.
Statistical precision would ordinarily be judged using an uncertainty measure, such as a confidence interval around the estimated difference. A confidence interval communicates the range of estimates compatible with the data under the analysis assumptions; it does not by itself establish clinical importance. No confidence interval for the co-primary efficacy comparison is reported in the registry record. The statistical test, its result, and any prespecified threshold for interpreting it are also not reported in the registry record.
There are safety counts in the registry record: 2 of 87 participants had serious adverse events, 41 of 87 had other adverse events, and 1 death was recorded. The record lists Electrocardiogram QT prolonged and Multiple organ dysfunction syndrome at 1.1% each among the top serious terms. These counts describe reported events, but the record does not provide enough information to infer whether an event was caused by Mangoral or to compare risk with an untreated or alternative-imaging group.
Accordingly, the available posted information supports a description of the intended diagnostic comparison, scoring approach, and recorded safety counts. It does not support a quantitative conclusion about the co-primary diagnostic results or a causal comparison of adverse-event risk.
9. Statistical Methods Explained
The registry describes a continuous endpoint summarized as a mean and standard deviation. In general, a mean represents the average of the values being analyzed, while the standard deviation describes how dispersed those values are around the mean. For this endpoint, the participant-level value is based on the ratings of assessed lesions, rather than being a score for a single lesion alone.
What does the participant-level score represent?
The lesion border delineation scale runs from 1 to 4, with higher values representing clearer distinction of the lesion border from liver background. The endpoint description says that up to 15 lesions per participant were assessed and that their individual scores were summed and averaged to calculate the participant's score. This creates a participant-level measure while retaining information from multiple lesions. The record does not say how many lesions were assessed for each participant or describe any weighting beyond the stated averaging procedure.
In general, a bounded rating scale is not the same as an unrestricted measurement: its possible scores are limited. Reporting a mean can be a concise way to summarize such ratings, but interpreting that mean still requires the scale definition and the distribution of scores. The registry describes the scale and its direction, but does not report the observed score distribution. It also does not report whether the primary comparison used a paired statistical method or another specified approach.
Why does the imaging comparison matter for interpretation?
The study is single-group, and the diagnostic question compares imaging methods rather than randomized treatment groups. A comparison of measurements from the same participant can have different statistical structure from a comparison of independent groups, because measurements from one participant may be related. In general, an analysis should account for the structure created by repeated or related measurements. The registry record does not report the exact model or test used for the co-primary comparison, so the handling of this structure cannot be assessed.
The record specifies central reading sessions by 3 independent, blinded readers. Blinding image readers can reduce the risk that knowledge of the imaging condition influences subjective ratings. However, the registry does not report reader-level results, a method for combining reader assessments, or a statistical model accounting for reader variation. Those details are not reported in the registry record.
How should uncertainty be assessed?
In general, an estimate should be read together with a measure of its uncertainty. A confidence interval expresses uncertainty about an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but precision is not the same as importance. A p-value, when reported, addresses compatibility between the data and a specified null model; it does not quantify the size of an effect or its practical meaning. The registry record does not report confidence intervals or p-values for the co-primary efficacy results.
Standard deviations and confidence intervals answer different questions. The standard deviation describes variation among the observed participant-level scores. A confidence interval describes uncertainty about an estimated quantity, such as a mean or a difference. One cannot be substituted for the other. Although the endpoint is described as a mean with standard deviation, the efficacy estimates themselves are not reported in the registry record.
What can planning illustrations tell readers?
In general, a sample-size calculation depends on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. The registry's planning illustrations are described as using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as stated fractions of the observed effect. These are planning illustrations, not the actual allocation or design of this single-group trial. The sample sizes in such illustrations are not observed power, and they should not be interpreted as the number enrolled or analyzed in this study.
The clinical trial's own sample-size justification and statistical plan are not reported in the registry record. The record also does not report the observed efficacy effect needed to evaluate the planning illustrations numerically. Therefore, those assumptions cannot be treated as evidence of the study's prespecified analysis or as a substitute for the missing efficacy estimates.
Why can over-dispersion matter?
In general, over-dispersion means that observed variability is greater than expected under a model's assumptions. If a statistical model underestimates variability, its uncertainty estimates may be too small and its test results may appear more decisive than warranted. Appropriate modeling depends on the data type and the structure of the observations. The registry record does not report an over-dispersion assessment or a model for the lesion-level or reader-level data, so no conclusion about this issue can be made for this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies two co-primary variables: lesion border delineation and lesion contrast. It also lists 13 outcome measures and 12 analyses. When more than one outcome or analysis is examined, the chance of obtaining at least one apparently strong result by chance can increase. In general, multiplicity procedures can control or describe this issue, but their choice depends on the planned hypotheses and analysis strategy.
The registry record does not report whether the co-primary variables had to meet a joint success criterion, how multiple comparisons were handled, or whether any multiplicity adjustment was used. It does not report a hierarchy among endpoints or a detailed prespecified testing plan. Without those details, the intended interpretation of multiple endpoint tests cannot be evaluated.
The Full Analysis Set is described as participants in the Safety Population who received the investigational product and had assessable primary efficacy variables, including assessable unenhanced and enhanced liver MRI images. The number included in the Full Analysis Set is not reported in the registry record. The complete population description is also not reported in the registry record.
Missing-data handling is not reported in the registry record. In general, missing imaging assessments can affect which participants contribute to an efficacy analysis, while excluding participants with incomplete data can change the population represented by the estimate. The record does not describe imputation, sensitivity analyses, or rules for incomplete reader or lesion assessments. It is therefore not possible to determine how missing images or unassessable lesions were handled.
The record refers to a Safety Population but does not provide its full definition in the available description. The relationship between that population and the reported safety counts is not explained further. These limits matter because a clear account of the analysis population and missing-data rules is needed to understand precisely which participants and observations contribute to each result.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Mangoral | 2 | 87 | 2.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Mangoral | 1 of 87 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Mangoral | 41 of 87 |
Most frequent serious adverse event terms
| Event term | Organ system | Mangoral |
|---|---|---|
| Electrocardiogram QT prolonged | Investigations | 1 of 87 |
| Multiple organ dysfunction syndrome | General disorders | 1 of 87 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Mangoral |
|---|---|---|
| Nausea | Gastrointestinal disorders | 14 of 87 |
| Diarrhoea | Gastrointestinal disorders | 12 of 87 |
| Vomiting | Gastrointestinal disorders | 8 of 87 |
| Blood urea increased | Investigations | 3 of 87 |
| Abdominal pain | Gastrointestinal disorders | 2 of 87 |
| Retching | Gastrointestinal disorders | 2 of 87 |
| Blood alkaline phosphatase increased | Investigations | 2 of 87 |
| Haemoglobin decreased | Investigations | 2 of 87 |
| White blood cells urine positive | Investigations | 2 of 87 |
| Haematuria | Renal and urinary disorders | 2 of 87 |
Serious events with the highest arm-level rate: electrocardiogram qt prolonged (1.1%), multiple organ dysfunction syndrome (1.1%).
The registry record lists 87 participants at risk for both serious and other adverse events. It records serious adverse events in 2 participants and other adverse events in 41 participants. A death is also recorded for 1 participant. These are counts, not comparative estimates against a separate control group.
The top serious adverse-event terms listed are Electrocardiogram QT prolonged at 1.1% and Multiple organ dysfunction syndrome at 1.1%. The registry record does not provide further event-level details, such as timing, duration, outcome, or whether the events were considered related to Mangoral. It also does not explain whether the recorded death was among the participants with serious adverse events, so that relationship should not be inferred.
In general, adverse-event counts describe what was recorded during a study; by themselves they do not establish causation. A comparison group and further information about exposure and follow-up would be needed to assess relative risk. The registry record does not report a like-for-like control group or enough detail to attribute the events to the imaging agent.
12. What the Result Does, and Does Not, Mean
The study's stated purpose is to assess the safety and diagnostic efficacy of Mangoral in liver MRI among participants with known or suspected focal liver lesions and severe renal impairment. Its diagnostic comparison concerns lesion visualization in combined MRI versus unenhanced MRI. The endpoint description explains how lesion border delineation was rated and how participant-level scores were formed.
That information clarifies what the study sought to measure, but it does not show the observed efficacy result. The registry record does not report the co-primary means, the difference between imaging methods, or uncertainty around that difference. It is therefore not possible to determine from the posted results whether lesion border delineation or lesion contrast was higher with either method, or how precise any difference was.
The trial's single-group design also limits what can be inferred about safety. The registry lists serious and other adverse-event counts and a death, but no separately assigned comparison group is described. Those observations cannot establish how the event counts compare with what would have occurred under another imaging approach. Nor do the counts by themselves establish that Mangoral caused an event.
More generally, a diagnostic image-rating result is not the same as evidence about downstream clinical outcomes. The listed endpoints focus on lesion detection, delineation, contrast, confidence, lesion size, and signal or contrast measures. The record does not provide results for these measures, nor does it report a link between image ratings and decisions or patient outcomes.
The appropriate interpretation is therefore bounded: the registry describes a study designed around an imaging-method comparison and reports selected safety counts, but it does not provide the numerical primary efficacy findings needed to judge the diagnostic comparison. The absence of those estimates in the registry record is not evidence that the methods were equivalent or that one performed better.
13. Why This Trial Matters Statistically
This study is statistically notable for asking a within-study imaging question in a population characterized by both focal liver lesions and severe renal impairment. The comparison is between unenhanced MRI and combined MRI incorporating Mangoral-enhanced and unenhanced images, rather than between separately randomized participant groups. That distinction affects how readers should understand the comparison and what causal claims are possible.
The endpoint also illustrates how an image-level assessment can be condensed to a participant-level summary. Multiple lesions could be rated for each participant, and the individual lesion scores were averaged to create a score bounded from 1 to 4. Such a summary can make participant-level comparisons easier to express, while potentially concealing variation among lesions. The record does not report lesion-level or participant-level distributions, so the extent of that variation cannot be assessed.
Central reading by 3 independent, blinded readers is relevant because lesion borders are judged on a qualitative scale. Reader blinding can reduce the influence of expectations on ratings, but interpretation still depends on the scoring rules and on how reader assessments are combined. Those additional statistical details are not reported in the registry record.
The record also demonstrates why endpoint definitions and outcome estimates need to be considered together. The scoring direction and timing are described, but the efficacy estimates and their uncertainty are not reported. Without those results, the endpoint definition cannot answer whether the imaging methods differed or how precisely a difference was estimated. Clear reporting of estimates, uncertainty, analysis populations, and missing-data methods would be needed for a fuller statistical interpretation.
14. 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 the diagnostic findings is that the registry record does not report the numerical co-primary efficacy results. The means, standard deviations, method-comparison estimates, uncertainty intervals, and test results are not reported in the registry record. This prevents assessment of the direction, magnitude, and precision of the primary comparison.
The study is listed as open-label, with no masking at the study level, and as a single-group study with allocation not applicable. Central reading sessions are described as involving 3 independent, blinded readers, but the record does not explain how blinding was maintained or how reader ratings were combined. There is no separately assigned control group for interpreting the safety counts.
The Full Analysis Set definition is incomplete in the registry record, and its analyzed participant count is not reported. Rules for missing or unassessable images, incomplete lesion ratings, and missing reader assessments are also not reported. These omissions make it difficult to determine exactly which observations contributed to the primary analysis.
The registry record does not report the statistical analysis plan, the testing approach for the co-primary variables, or how multiplicity was addressed. It also does not report the trial's sample-size justification. Planning illustrations are described using assumptions that do not match the trial's single-group design; they should not be mistaken for the trial's actual design or observed power.
For safety, counts are reported, but event timing, attribution, follow-up details, and the relationship between the death and serious adverse events are not reported in the registry record. The available information therefore supports descriptive reporting of the listed counts, not a causal or comparative safety conclusion.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Diagnostic Efficacy of Mangoral in Participants With Focal Liver Lesions and Reduced Kidney Function — NCT04119843.
- Registry record last updated 2025-02-06; status last verified 2025-01.
- Results first posted 2025-02-06.
- 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.
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18. Record Summary
NCT04119843 is a completed Phase 3, multicenter, open-label, single-group study of Mangoral in participants with known or suspected focal liver lesions and severe renal impairment. The registry record lists 87 enrolled participants. All participants received a single dose of Mangoral, described as 800 mg Manganese (II) chloride tetrahydrate.
The co-primary diagnostic assessment compared lesion border delineation and lesion contrast in combined MRI with unenhanced MRI. The detailed border-delineation measure used a 1-to-4 scale, with higher scores representing clearer lesion borders, and central reading was conducted by 3 independent, blinded readers.
The registry record lists serious adverse events in 2 of 87 participants, other adverse events in 41 of 87, and 1 death. It does not report the numerical co-primary efficacy results, the full statistical analysis plan, or the methods used for missing data and multiplicity.