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 Dialysability of Dotarem® in Dialysed Patients (NCT01449266), a na phase 1 study. The primary outcome is Dialysability of Dotarem® in Dialysed Patients.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01449266 |
| Phase | Phase 1 |
| Condition | End-stage Renal Failure |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Guerbet |
| Results posted | Yes |
2. Clinical Question
Population
Male or female adults aged ≥18 years with end-stage renal failure who required hemodialysis treatment 3 times per week. The registry record lists an enrollment of 10.
Intervention
A single intravenous injection of Dotarem® at 0.1 mmol/kg.
Comparator
There was no comparator group. The design is listed as single-group, with allocation recorded as not applicable and masking as none.
Primary question
How did serum gadolinium concentration change after hemodialysis sessions following Dotarem® administration, with dialysability assessed up to 4 days after administration?
The primary question concerns the change in serum gadolinium concentration across hemodialysis, not a comparison of Dotarem® with another contrast agent, a placebo, or no injection. The registry describes estimating concentration before and after each dialysis session and calculating percent change for subjects whose concentration was above the lower limit of quantification.
The record also identifies safety as a secondary outcome, assessed by the number of patients experiencing adverse events. It reports adverse-event counts and a list of serious-event terms, but those safety data do not answer the dialysability question. Conversely, a concentration change is not itself a safety outcome. The registry record does not report the numerical results for the primary endpoint or the secondary safety outcome definitions beyond the stated event count measure.
3. Trial Design
This is a completed phase 1 clinical study registered as NCT01449266, titled “Safety and Dialysability of Dotarem® in Dialysed Patients.” The sponsor is Guerbet. The registry lists a start date of 2011-11 and a primary completion date of 2012-03. Enrollment is 10, and the listed condition is end-stage renal failure.
The design is single-group, with allocation recorded as not applicable and masking recorded as none. Participants received a single Dotarem® intravenous injection at 0.1 mmol/kg before undergoing 3 hemodialysis sessions. The purpose of measuring serum gadolinium concentration around dialysis was to assess its decrease after treatment. Because there is no comparator group, the design does not provide a randomized or concurrent control comparison.
The primary outcome is dialysability, expressed as percent change in gadolinium concentration. It is assessed up to 4 days after Dotarem® administration. The record says that the calculation uses concentrations measured before and after each hemodialysis session, and that calculations include only subjects with concentrations above the lower limit of quantification. After the second hemodialysis session, 3 subjects had concentrations below that limit and were not included in the analysis; after the third session, 8 subjects were below the limit and were not included.
The registry lists 4 outcome measures and 0 analyses. It does not report the statistical analysis plan, the rationale for the enrollment target, interim analyses, or additional details about the sequence or timing of measurements beyond the endpoint description. The record’s design features therefore support a descriptive, within-group assessment, but the extent of planned inferential analysis is not reported in the registry record.
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
| Stage | Dotarem® Injected Patients |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: After second hemodialysis, 3 subjects had Gd concentration\<LLQ and are not included in the analysis; after third hemodialysis, 8 subjects had Gd concentration\<LLQ and are not included in the analysis
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: No statistical calculation of sample size was done. According to the literature, a sample of 10 patients was judged sufficient to evaluate the dialysability of Dotarem®.
| Characteristic | Unit | Dotarem®-Injected Patients |
|---|---|---|
| Participants analysed | 10 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 5 |
| Age, Categorical: >=65 years | Participants | 5 |
| Age, Continuous | years | 64.0 (31 to 79) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 5 |
| Region of Enrollment: Belgium | participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Dialysability of Dotarem® in Dialysed Patients, measured over Dotarem® dialysability assessed up to 4 days after Dotarem® administration.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Full Range |
| Unit | percent change in Gd concentration |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint measures the percent change in serum gadolinium concentration around hemodialysis sessions after a single Dotarem® injection at 0.1 mmol/kg. Concentration is estimated before and after each session. The registry states that the endpoint uses a geometric mean and that dispersion is described by the full range. The stated assessment period is up to 4 days after administration.
Dialysis removes substances from the blood, so tracking concentration around dialysis sessions is a way to describe the change associated with those sessions. In general, a before-and-after concentration measure can characterize the direction and size of a change within the observed group. It does not, by itself, separate the effect of dialysis from other changes over time or establish how the same patients would have changed without dialysis.
The calculation is restricted to subjects whose gadolinium concentration is above the lower limit of quantification. Values below that analytical limit cannot be treated as exact measured concentrations using the stated approach. The record reports that this affected 3 subjects after the second hemodialysis and 8 subjects after the third, who were excluded from the respective analyses. Numerical endpoint estimates, ranges, and uncertainty intervals are not reported in the registry record, so the magnitude and precision of the observed concentration changes cannot be assessed from the registry results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the study question and endpoint but does not report numerical results for the primary dialysability outcome. It therefore does not establish the size, direction, or precision of the percent change in serum gadolinium concentration after any hemodialysis session. A description of how an outcome was calculated is not a result for that outcome.
The intended comparison is within the injected group, using concentrations measured before and after dialysis. This can describe the concentration pattern among participants with measurements above the lower limit of quantification. It is not a treatment-versus-control contrast. With a single-group design, the record cannot provide a like-for-like estimate against an untreated or alternative-treatment group, and it does not identify the counterfactual concentration pattern that would have occurred without the injection or dialysis.
The analysis population also changes across the stated post-session measurements because concentrations below the lower limit of quantification were excluded. After the second hemodialysis, 3 subjects were not included in the analysis for being below that limit; after the third, 8 subjects were not included. This does not mean that those concentrations were zero. It means the concentrations were below the stated measurement threshold and were not used in the calculation. Without the numerical results or further detail on handling values below the limit, the extent to which this affects the reported endpoint cannot be quantified.
For safety, the registry reports 4 of 10 patients experiencing serious adverse events and 8 of 10 experiencing other adverse events. It also lists serious-event terms with percentages. These are descriptive counts and listed terms; the record does not establish that the events were caused by Dotarem®. The registry does not report deaths. The safety information should be read separately from the primary concentration endpoint, and neither the event counts nor the endpoint description constitute a comparison with another group.
Any sample-size illustrations associated with the posted results are planning calculations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The record does not report the trial’s own sample-size justification, and this single-group study does not itself provide a two-arm comparison. No calculated planning values should be interpreted as trial outcomes.
9. Statistical Methods Explained
What does a geometric mean describe?
A geometric mean summarizes measurements by averaging on a multiplicative scale rather than by taking a simple arithmetic average. In general, it is useful for positive measurements that vary proportionally or have a skewed distribution. It describes a central value, but does not show every participant’s measurement or the spread on its own. The registry pairs the geometric mean with the full range, which describes the lowest and highest observed values included in the relevant calculation. No numerical geometric means or ranges are reported in the registry record.
What does percent change mean for this endpoint?
The endpoint uses serum gadolinium concentrations measured before and after a hemodialysis session to calculate percent change. In general, a percent change expresses a change relative to a starting measurement, rather than reporting only the absolute difference in measurement units. Here, the registry does not provide the actual concentrations or calculated changes, so the direction and size of any change cannot be described. It also does not report whether results were aggregated across sessions or how session-specific estimates were combined.
Why does the lower limit of quantification matter?
The lower limit of quantification is the lowest concentration that the measurement procedure can quantify under its stated conditions. A result below that limit is not an exact measured concentration suitable for the calculation described in this record. It is not equivalent to a concentration of zero. The registry says that only subjects with concentrations above the limit were included in the calculations. After the second hemodialysis, 3 subjects were below the limit; after the third, 8 subjects were below it. The registry record does not report a method for assigning numerical values to those below-limit measurements or including them through another statistical approach.
What can a within-group before-and-after analysis show?
In general, measurements taken before and after an event can describe how the measured outcome changed in the observed group. Repeated measurements can also show whether the concentration pattern differs across the dialysis sessions. However, without a comparator group, a before-and-after pattern alone cannot distinguish the effect of dialysis from other time-related influences, measurement variability, or changes in the participants’ condition. It cannot make a randomized contrast between Dotarem® and another approach. The registry identifies a single-group design and does not report an adjusted model or a formal inferential analysis.
What does the reported dispersion tell the reader?
The full range gives the span from the lowest to the highest included observations. In general, a range is sensitive to extreme observations and does not indicate how values are distributed between its endpoints. It is different from a confidence interval, which is an interval intended to express uncertainty about an estimated quantity under a statistical model. The registry does not report confidence intervals, standard errors, or numerical ranges for the primary endpoint. Therefore, readers cannot assess the precision of the estimated changes or distinguish a narrowly estimated result from one with substantial uncertainty.
Why might over-dispersion matter?
As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. If a model underestimates variability, uncertainty can appear smaller than it is, affecting confidence intervals and tests. This matters particularly when data are more variable than a simple model expects. The registry record does not state that over-dispersion was assessed, nor does it report a model for the primary outcome. It is therefore not possible to say whether it was relevant to the sponsor’s analysis.
How should planning calculations be interpreted?
Sample-size calculations are planning exercises that ask how many participants might be needed under specified assumptions to detect a target effect with a chosen statistical procedure. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target defined as a stated fraction of the observed effect. Such calculations are hypothetical illustrations, not evidence about the precision or success of this study. They are not observed power. The record does not report a trial-specific sample-size justification, and no two-arm comparison is described in the study design.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 4 outcome measures and 0 analyses. It identifies the dialysability measure as primary and lists safety, assessed by the number of patients experiencing adverse events, as a secondary outcome. The registry record does not report whether additional outcomes were prespecified in a hierarchy, whether any adjustment for multiple testing was planned, or how the primary and secondary outcomes were to be interpreted together. No p-values or confidence intervals for the primary outcome are reported.
The primary endpoint has analysis-population exclusions tied to the lower limit of quantification. After the second hemodialysis, 3 subjects with concentrations below that limit were not included; after the third, 8 subjects were not included. This is a measurement-threshold issue, not necessarily ordinary loss to follow-up. The record does not report whether those subjects had other missing measurements, whether below-limit values were handled in any alternative analysis, or whether sensitivity analyses were conducted.
The registry record does not describe an intention-to-treat population, a per-protocol population, or other formal analysis populations for the primary endpoint. It also does not report imputation procedures, a missing-data model, or an analysis population definition beyond the above-limit restriction. Safety counts are reported for 10 patients at risk, but the record does not provide further detail on the safety analysis population or the handling of missing safety information. Because results and analysis methods are not fully reported, the effect of missing or excluded measurements and any multiplicity considerations cannot be evaluated.
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 |
|---|---|---|---|
| Dotarem® Injected Patients | 4 | 10 | 40.0% |
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 |
|---|---|
| Dotarem® Injected Patients | 8 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Dotarem® Injected Patients |
|---|---|---|
| moderate sepsis | Infections and infestations | 2 of 10 |
| severe respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 10 |
| severe peripheral ischemia | Vascular disorders | 1 of 10 |
| moderate thrombocytopenia | Blood and lymphatic system disorders | 1 of 10 |
| severe urosepsis | Infections and infestations | 1 of 10 |
| Dialysis device insertion | Surgical and medical procedures | 1 of 10 |
| Nephrectomy | Surgical and medical procedures | 1 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dotarem® Injected Patients |
|---|---|---|
| Hypotension | Vascular disorders | 5 of 10 |
| Headache | Nervous system disorders | 3 of 10 |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 3 of 10 |
| Anemia | Blood and lymphatic system disorders | 1 of 10 |
| Abdominal pain | Gastrointestinal disorders | 1 of 10 |
| influenza-like illness | General disorders | 1 of 10 |
| thirst | General disorders | 1 of 10 |
| Procedural pain | Injury, poisoning and procedural complications | 1 of 10 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1 of 10 |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 1 of 10 |
Serious events with the highest arm-level rate: moderate sepsis (20.0%), severe respiratory failure (10.0%), severe peripheral ischemia (10.0%), moderate thrombocytopenia (10.0%), severe urosepsis (10.0%).
The registry reports that 4 of 10 patients experienced serious adverse events and that 8 of 10 experienced other adverse events. These are counts of patients, not a rate per unit of follow-up. The record lists serious-event terms and percentages: moderate sepsis, 20.0%; severe respiratory failure, 10.0%; severe peripheral ischemia, 10.0%; moderate thrombocytopenia, 10.0%; severe urosepsis, 10.0%; and Dialysis device insertion, 10.0%.
The registry does not report whether the listed terms overlap within patients, so they should not be added together or treated as mutually exclusive categories. The record also does not state that these events were caused by Dotarem®. The figures describe events recorded in the study group; they do not establish causality or provide a comparison with another group. Deaths are not reported in the registry record. The secondary outcome is described as the number of patients experiencing adverse events, but additional details about event collection, follow-up, or attribution are not reported.
12. What the Result Does, and Does Not, Mean
This study addresses a focused measurement question: how serum gadolinium concentration changed around hemodialysis after a single Dotarem® injection in patients with end-stage renal failure who required regular hemodialysis. It provides a study design and an endpoint definition suited to describing concentrations around dialysis sessions. However, the registry record does not report numerical primary outcome results, so the magnitude and precision of dialysability cannot be determined from the posted results.
The study is single-group and has no comparator. Any observed before-and-after change would describe the participants with qualifying measurements, but would not establish how concentrations would have changed under an alternative contrast agent or without the study procedure. The record also excludes below-limit concentrations from specified calculations. The number excluded differs by session: 3 subjects after the second hemodialysis and 8 subjects after the third. This limits what can be inferred about the later-session measurements from the stated analysis population.
The safety information records serious and other adverse events, including listed serious-event terms. Those observations do not by themselves establish that Dotarem® caused the events, and the registry does not report a control group for comparison. The event counts should therefore be interpreted as descriptive findings for this study group rather than comparative estimates.
Overall, the record documents that a phase 1 study was completed and defines its dialysability and safety questions. It does not report enough outcome or analysis detail to quantify a treatment effect, assess its statistical precision, or support a comparative conclusion. It does not show that a treatment works or does not work; those claims are not established by the registry information reported for this study.
13. Why This Trial Matters Statistically
This trial illustrates how a clinical question can be framed around a measurable pharmacologic process rather than a comparison of clinical outcomes. Its primary endpoint tracks serum gadolinium concentration before and after hemodialysis, and its design follows a single group after a single injection. That structure makes clear why design and endpoint interpretation must be considered together: a concentration pattern can describe what was measured in the group, but the absence of a comparator limits causal and comparative interpretation.
It also highlights how assay limits shape the analysis population. Measurements below the lower limit of quantification are not exact quantified concentrations, and excluding them changes which observations contribute to the calculation. The registry notes exclusions after the second and third hemodialysis sessions but does not report alternative handling or sensitivity analyses. That makes transparent reporting of threshold-related exclusions important for understanding what an estimate represents.
Another statistical lesson is the distinction between an endpoint definition and an endpoint result. The registry specifies the geometric mean, full range, percent-change measure, and assessment period, yet the numerical primary outcome results are not reported. Without estimates and uncertainty measures, readers cannot judge magnitude or precision. The listed adverse-event counts similarly require careful interpretation: descriptive safety observations are not causal comparisons, especially in a single-group study.
Finally, planning calculations should not be confused with evidence generated by the trial. The record describes assumptions for sample-size illustrations, but these are hypothetical planning exercises rather than observed power or a report of the study’s own design justification. The case demonstrates why estimates, analysis populations, uncertainty, and comparator structure all matter when translating registry records into statistical conclusions.
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 primary question is that the registry record does not report numerical dialysability results. It describes percent change in serum gadolinium concentration and the use of a geometric mean with full range, but gives no endpoint estimates or uncertainty measures. Thus, the magnitude, direction, and precision of the primary outcome cannot be assessed from the record.
The study is single-group, with no like-for-like control comparison. The registry lists allocation as not applicable and masking as none. A within-group concentration change cannot by itself isolate the contribution of dialysis from other time-related factors or establish a comparative effect of Dotarem®.
The analysis excludes subjects whose concentrations were below the lower limit of quantification for the relevant calculation. This applied to 3 subjects after the second hemodialysis and 8 subjects after the third. The record does not report how those values were handled in any alternative analysis, whether sensitivity analyses were performed, or how the changing analysis population affected interpretation.
Additional limitations are that the registry does not report a statistical analysis plan, confidence intervals, p-values, the rationale for the enrollment target, or details of missing-data methods. Safety findings are descriptive, and the record does not establish event attribution. These omissions restrict assessment of precision, potential bias, and the basis for statistical conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Dialysability of Dotarem® in Dialysed Patients — NCT01449266.
- Registry record last updated 2015-07-08; status last verified 2015-06.
- Results first posted 2015-06-08.
- 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
NCT01449266 is a completed phase 1, single-group study sponsored by Guerbet, with enrollment of 10. It evaluated Dotarem® dialysability and safety in patients with end-stage renal failure receiving hemodialysis. Participants received a single intravenous injection at 0.1 mmol/kg before 3 hemodialysis sessions.
The primary endpoint was percent change in serum gadolinium concentration, using a geometric mean and full range, assessed up to 4 days after administration. Calculations included subjects with concentrations above the lower limit of quantification; 3 subjects were excluded after the second session and 8 after the third because their concentrations were below that limit. Numerical primary outcome results are not reported in the registry record.
The registry reports serious adverse events in 4 of 10 patients and other adverse events in 8 of 10, with serious-event terms listed. It does not report a comparator group or deaths. The registry lists 4 outcome measures and 0 analyses, and does not report the statistical analysis plan or trial-specific sample-size justification.