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 Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients (NCT01818726), a randomized phase 4 study. The primary outcome is Change in Serum Ferritin Values.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01818726 |
| Phase | Phase 4 |
| Condition | Aplastic Anemia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Transfusion-dependent adults with aplastic anemia receiving programmed immunosuppressive treatment with cyclosporine A. The record describes ferritin-defined groups, with one arm description specifying serum ferritin ≥ 1,000 μg/l and another specifying serum ferritin < 1,000 μg/l.
Intervention
Exjade, also identified as deferasirox, used as chelation therapy alongside cyclosporine A in the group described as having serum ferritin ≥ 1,000 μg/l.
Comparator
A group described as receiving cyclosporine A without chelation therapy. Its arm description identifies the group by serum ferritin < 1,000 μg/l and says participants were not receiving the investigational product.
Primary question
How did mean serum ferritin change from baseline over the scheduled study visits in the treatment groups? The registry record says change from baseline was to be summarized descriptively, but no efficacy analysis was performed.
The central question concerns changes in serum ferritin, a laboratory measure used in the clinical context of transfusion-dependent iron overload. The study description frames the comparison as chelation with Exjade added to cyclosporine A versus cyclosporine A without chelation. However, the arm descriptions also distinguish participants according to ferritin threshold, rather than presenting treatment assignment alone as the basis for the groups. The registry identifies allocation as randomized, but details of how randomization was implemented, and how that designation relates to the ferritin-defined arm descriptions, are not reported in the registry record. This matters when interpreting a comparison: a difference between groups cannot automatically be attributed to chelation if the groups also differ in how they were defined or assigned. The posted results do not give numerical ferritin changes, estimates of uncertainty, or a formal comparison. The record therefore establishes the intended clinical question, but does not provide an analyzed estimate that answers it.
3. Trial Design
The registry describes a Phase 4, randomized, open-label, parallel-group study sponsored by Novartis Pharmaceuticals. The study concerned adults with aplastic anemia and transfusion-dependent iron overload who were receiving immunosuppressive treatment with cyclosporine A. The intervention was Exjade (deferasirox) chelation, compared with a group described as receiving cyclosporine A without chelation. The study started on 2014-06-23, and the primary completion date is listed as 2016-10-17. Its current status is terminated. Enrollment is recorded as 15.
The registry says masking was none, so the design is described as open-label. It identifies the study as randomized, but does not report the randomization procedure, allocation concealment, or details about how participants were assigned to groups. The arm descriptions are based on serum ferritin categories: one describes participants with levels ≥ 1,000 μg/l receiving chelation, and the other describes participants with levels < 1,000 μg/l who were not receiving the investigational product. The descriptions also differ in the treatment received, as well as the ferritin category. How this arm structure relates to the randomized allocation is not reported in the registry record.
The stated primary endpoint was change in serum ferritin values. The planned timeframe lists Screening and visits from Week 4 through Week 52. The record says change from baseline was to be summarized descriptively at on-treatment visits. It also explains that a planned per-protocol efficacy analysis was not performed after substantial discontinuation and protocol deviations affecting efficacy assessment. The registry does not report a completed primary efficacy analysis. Further details on eligibility, randomization, treatment duration, adherence, or the reasons for termination are 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.
Before assignment: The study enrolled adult transfusion-dependent patients with Aplastic Anaemia (AA) on programmed immune suppressive treatment.
Overall Study
| Stage | Serum Ferritin Level ≥ 1,000 μg/l | Serum Ferritin Level < 1,000 μg/l |
|---|---|---|
| STARTED | 10 | 5 |
| COMPLETED | 4 | 3 |
| NOT COMPLETED | 6 | 2 |
Reasons for not completing this period:
| Reason | Serum Ferritin Level ≥ 1,000 μg/l | Serum Ferritin Level < 1,000 μg/l |
|---|---|---|
| Administrative reasons | 5 | 1 |
| Withdrawal by Subject | 0 | 1 |
| Decision to perform 2nd course of trtmnt | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set included all patients of the Safety Analysis Set with available baseline data \& data obtained at follow-up visits \&/or final visit, for evaluation of at least 1 efficacy parameter. Statistical analysis was not performed due to large number of patients discontinuing \& thus lack of assessments of iron exchange parameters at visits.
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 Analysis Set included all enrolled patients received at least one dose of the investigational product, as well as all patients from the comparison group.
| Characteristic | Unit | Serum Ferritin Level ≥ 1,000 μg/l | Serum Ferritin Level < 1,000 μg/l | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 5 | 15 | |
| Age, Continuous | Years | 34.0 (SD 9.33) | 37.0 (SD 10.10) | 35.0 (SD 9.34) |
| Sex: Female, Male: Female | Participants | 6 | 4 | 10 |
| Sex: Female, Male: Male | Participants | 4 | 1 | 5 |
| Race/Ethnicity, Customized: Caucasian | Participants | 10 | 5 | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Serum Ferritin Values, measured over Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ng/ml |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in serum ferritin values, expressed in ng/ml, with the measure described as a mean and its dispersion as a standard deviation. The listed timeframe begins at Screening and includes scheduled assessments at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, and Week 52. The registry states that change from baseline was to be summarized descriptively for all on-treatment study visits.
In general, serum ferritin is used as a laboratory indicator related to the body’s iron stores, so tracking its change is relevant to a study of transfusion-dependent iron overload and chelation. A mean summarizes the average observed change within a group; a standard deviation describes the spread of individual measurements around that mean. These summaries can describe the direction and variability of observed measurements, but by themselves do not establish a treatment effect. Interpreting a between-group difference also requires information about the analysis population, missing observations, and how the groups were formed.
The registry record provides no numerical results for this endpoint and says statistical analysis was not performed because of discontinuations and limited availability of assessments. Thus, the endpoint is specified, but the posted record does not establish the size, direction, or precision of any ferritin change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies change in serum ferritin as the primary efficacy outcome and describes a planned descriptive summary across scheduled visits. It does not, however, provide numerical ferritin results or a formal comparison between groups. The record states that statistical analysis was not performed because many participants discontinued and assessments of iron exchange parameters were lacking. It also says an additional per-protocol efficacy analysis was not performed because of substantial withdrawal from the Per-Protocol Analysis Set and protocol deviations affecting efficacy assessment. As a result, the posted record does not estimate the treatment contrast posed by the study question.
This absence is different from a finding of no change or no difference. Without reported group means, changes from baseline, or a treatment contrast, the direction and magnitude of the observed response cannot be assessed. Without a confidence interval or other uncertainty measure for a contrast, its precision cannot be assessed either. The stated endpoint uses a mean and standard deviation, but the registry does not give those outcome values. No p-value or inferential result is reported in the registry record.
The design description also calls for care in interpreting any apparent group contrast. Although the study is labeled randomized, its arm descriptions distinguish the groups by ferritin thresholds and by whether participants received chelation. Details reconciling those descriptions with random assignment are not reported in the registry record. A randomized comparison can support causal interpretation when allocation and analysis preserve the randomized groups, but that general principle cannot fill gaps in the account of this study. The record does not describe the assignment process or a completed analysis using assigned groups.
There is a further unit inconsistency in the descriptions: arm titles use μg/l, while the text for the arms states mg/L. The record does not explain whether these are intended to refer to the same threshold. This uncertainty should not be resolved by assuming a correction. The endpoint unit is separately listed as ng/ml.
The record’s status is terminated, and enrollment is 15. These registry entries describe the study’s conduct, but do not quantify the effect of treatment. No conclusion about efficacy can be drawn from the absence of an efficacy result. The safety entries report serious adverse event counts by group, but they do not substitute for the missing efficacy analysis or provide a complete account of other safety outcomes. Overall, the registry describes a planned study question and some safety counts, while leaving the primary treatment comparison unanswered.
9. Statistical Methods Explained
The statistical details in the registry are limited. The record names a continuous outcome, a mean summary, and standard deviation as the measure of dispersion. It says changes from baseline were to be summarized descriptively at on-treatment visits. It does not report a completed efficacy analysis, inferential model, treatment-effect estimate, or confidence interval. The following concepts explain how such analyses are generally interpreted; they are not claims about methods used in this study unless expressly described in the registry.
What does a mean change describe?
For a continuous measurement, change from baseline represents how a participant’s measurement at a follow-up visit differs from their baseline measurement. A group mean change averages these participant-level changes among the observations included in the analysis. It provides a compact description of the group’s average trajectory, while the standard deviation describes variability among observed values. A mean can conceal variation: participants may have changes in different directions or of different sizes even when the group average is close to a particular value. The registry record does not give the means or standard deviations for this endpoint, so no such pattern can be examined.
Why does a between-group comparison need more than two summaries?
Comparing group averages can be useful, but a valid treatment interpretation depends on the design and analysis. In a randomized study, the intended comparison ordinarily follows the groups as assigned, so the comparison retains the protection offered by random allocation. The registry labels this study randomized, but does not report assignment details or a completed analysis by assigned group. It instead describes arms using ferritin thresholds as well as receipt or non-receipt of chelation. The available record does not explain the relationship between these arm descriptions and the stated randomization. It is therefore not possible to reconstruct a treatment contrast from the registry narrative.
In general, a confidence interval gives a range of values compatible with the observed data under the analysis assumptions and communicates uncertainty around an estimate. A narrow interval indicates greater precision than a wide interval, though neither alone establishes that an effect is clinically important. No confidence interval for serum ferritin change is reported in the registry record. A p-value, if reported, would address compatibility with a statistical null model under specified assumptions; it would not by itself describe effect size or clinical relevance. The registry record does not report a p-value for this outcome.
What can descriptive summaries establish?
Descriptive statistics can show what was observed in the analyzed participants. They do not automatically separate treatment effects from baseline differences, selection into the analysis, or differences in follow-up. This is particularly relevant when follow-up is incomplete. If participants with missing visits differ in outcome or prognosis from those who remain, a summary restricted to available measurements may not represent the full group originally enrolled. General methods for handling missing data require assumptions about why observations are missing and an analysis plan suited to those assumptions. The registry does not report a missing-data method or enough detail to judge those assumptions.
Repeated measurements across visits can be analyzed in different ways. A visit-by-visit descriptive approach summarizes each scheduled assessment separately; a longitudinal model can use repeated measurements while accounting for within-participant correlation. These approaches answer related but not identical questions and rely on different assumptions. The registry says the changes were to be summarized descriptively at on-treatment visits, but does not give details of a model for repeated measures. It should not be inferred that a longitudinal model, adjustment, or other method was used.
What does the record say about the analysis population?
The Full Analysis Set is described as including patients from the Safety Analysis Set with available baseline data and data at follow-up visits and/or a final visit for evaluation of at least one efficacy parameter. The recorded population description is truncated. The registry also states that efficacy analysis was not performed because of discontinuations and lack of assessments. It therefore does not provide results for this stated population. The planned per-protocol efficacy analysis was additionally not performed, with the record citing withdrawals and protocol deviations affecting efficacy assessment. The analysis population used for any reported primary endpoint estimate cannot be identified because no such estimate is reported.
Are the sample-size illustrations evidence of power?
In general, a sample-size calculation is a planning exercise based on assumptions about a target effect, variability, allocation, and a chosen error rate. It is not a measure of what the completed study actually detected. The record describes planning illustrations based on fractions of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It explicitly distinguishes these planning illustrations from the trial’s own design and states that participant counts are per arm for non-time-to-event outcomes. Such illustrations should not be read as observed power or as evidence that a treatment effect was present. Because the primary efficacy analysis was not performed and no observed effect estimate is reported, the registry does not establish an effect on which to base an empirical efficacy conclusion.
Overall, the methodological account supports a limited reading: the outcome and intended descriptive approach are named, and the reasons for not conducting efficacy analyses are summarized. The statistical plan, handling of repeated measures and missing data, and inferential comparison are not reported in the registry record. General statistical concepts cannot supply those missing study-specific details.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint is measured repeatedly, with scheduled assessments from Screening through Week 52. Multiple visits create several possible descriptions of change, but the registry does not identify a single visit as the sole time point for a treatment comparison. It says change from baseline was to be summarized descriptively at all on-treatment study visits. No adjustment for multiple comparisons, hierarchy among visits, or strategy for identifying a primary time-specific contrast is reported in the registry record. The record’s note that the primary outcome has several categories or time points and was not reduced to one comparison is consistent with avoiding an unsupported single-visit result.
Missingness is a material concern in the registry’s own account. The record attributes the lack of efficacy analysis to a large number of discontinuations and the resulting lack of assessments of iron exchange parameters at visits. It also cites protocol deviations affecting efficacy assessment as a reason not to conduct the per-protocol analysis. The reasons participants discontinued, the timing of missing visits, and the relationship between missingness and outcome are not reported in the registry record.
The Full Analysis Set is described as drawn from the Safety Analysis Set and requiring available baseline and follow-up and/or final-visit data for evaluation of at least one efficacy parameter. The description is incomplete in the record. The record does not specify a missing-data method, an imputation strategy, or sensitivity analyses. In general, analyses based only on available measurements can be biased if availability is related to outcome; methods addressing missing data rely on assumptions that should be made explicit. No such assumptions or methods are reported.
The registry states that neither the primary efficacy analysis nor the additional per-protocol efficacy analysis was performed. Consequently, there is no reported result to interpret across visits or analysis populations, and no reported multiplicity procedure to assess.
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 |
|---|---|---|---|
| Serum Ferritin Level ≥ 1,000 μg/l | 0 | 10 | 0.0% |
| Serum Ferritin Level < 1,000 μg/l | 0 | 5 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Serum Ferritin Level ≥ 1,000 μg/l | 0 of 10 |
| Serum Ferritin Level < 1,000 μg/l | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Serum Ferritin Level ≥ 1,000 μg/l | 4 of 10 |
| Serum Ferritin Level < 1,000 μg/l | 0 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Serum Ferritin Level ≥ 1,000 μg/l | Serum Ferritin Level < 1,000 μg/l |
|---|---|---|---|
| Blood creatine increased | Investigations | 2 of 10 | 0 of 5 |
| Nausea | Gastrointestinal disorders | 1 of 10 | 0 of 5 |
| Weakness | General disorders | 1 of 10 | 0 of 5 |
| Rash | Skin and subcutaneous tissue disorders | 1 of 10 | 0 of 5 |
| Constipation | Gastrointestinal disorders | 1 of 10 | 0 of 5 |
| Diarrhea | Gastrointestinal disorders | 1 of 10 | 0 of 5 |
The registry reports serious adverse event figures separately for the ferritin-defined groups. In the group titled Serum Ferritin Level ≥ 1,000 μg/l, 10 participants are listed as at risk for serious adverse events and 0 as affected. The other adverse event figures list 10 at risk and 4 affected. In the group titled Serum Ferritin Level < 1,000 μg/l, 5 are listed as at risk for serious adverse events and 0 as affected; the other adverse event figures list 5 at risk and 0 affected. Deaths are listed as 0 in both groups.
These entries are counts, not estimates of comparative risk. They do not show whether the reported other adverse events were serious, what events occurred, when they occurred, or how severity was assessed. The registry lists no top serious adverse event terms. The groups are described differently in both ferritin category and chelation exposure, so these figures should not be read as a clean randomized treatment contrast. Small group counts also make the absence of recorded serious events insufficient to establish that serious events cannot occur. The registry does not provide additional safety detail in this record.
12. What the Result Does, and Does Not, Mean
The record establishes that a study was registered to assess Exjade (deferasirox) chelation in adults with aplastic anemia and transfusion-dependent iron overload receiving cyclosporine A. It also establishes that the intended primary outcome was change in serum ferritin, with descriptive summaries planned across on-treatment visits. These are details about the study question and its planned outcome, not evidence of a treatment effect.
The posted results do not report numerical primary endpoint values or a between-group efficacy estimate. The registry says the planned efficacy analysis was not performed because of discontinuations and unavailable assessments, and that the per-protocol analysis was also not performed. This means the study record does not show whether serum ferritin increased, decreased, or remained similar between groups. It does not show how precise any such difference would have been. A missing result must not be interpreted as evidence that there was no effect, nor as evidence that an effect occurred.
The record labels allocation randomized, but the arm descriptions use ferritin thresholds and distinguish chelation exposure. Details reconciling these features are not reported in the registry record. Without a clear account of assignment and an analysis of the intended groups, even a numerical contrast would require careful interpretation; here, no efficacy contrast is reported at all. The unit wording for the arm thresholds also differs between the arm titles and descriptions.
The safety entries report zero serious adverse events and zero deaths in the listed groups, while other adverse event counts are recorded for one group. These sparse registry figures do not give a full safety profile or support a comparative safety conclusion. The study’s terminated status and enrollment are relevant context, but they do not explain the reasons for termination or resolve the missing efficacy results. The record therefore documents a planned clinical question and limited safety counts, while leaving the primary question unanswered.
13. Why This Trial Matters Statistically
This study illustrates why a registered clinical question and an interpretable result are not the same thing. The record specifies a clinically relevant endpoint, change in serum ferritin, and identifies a planned comparison involving chelation alongside cyclosporine A. Yet the registry also states that substantial discontinuation and missing assessments prevented the efficacy analysis. Without the outcome summaries or a treatment contrast, readers cannot assess the magnitude, direction, or precision of the result.
The record also highlights the importance of transparent analysis populations. It describes a Full Analysis Set and explains why the per-protocol analysis was not conducted, but the recorded population description is truncated and no efficacy estimate is presented. Clear reporting of who contributed measurements, how incomplete follow-up was handled, and which groups were compared is essential when attrition affects the planned analysis.
Another statistical issue is the distinction between a randomized label and evidence that a reported comparison preserves randomized assignment. Here, the study is identified as randomized, while its arm descriptions classify participants by ferritin threshold and treatment exposure. The registry does not explain how those descriptions relate to assignment. That ambiguity cautions against treating the listed groups as interchangeable with a clearly documented randomized contrast.
Finally, repeated assessments can create multiple possible summaries, and the record does not report a multiplicity strategy or a selected time-specific comparison. The outcome is described across visits, but no efficacy analysis was completed. The statistical significance of this record lies in the limits of what can be concluded: design labels, planned endpoints, and safety counts cannot replace an analyzed outcome with transparent uncertainty.
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.
Several limitations specific to this record constrain interpretation. The study is listed as terminated, but the reason for termination is not reported in the registry record. Enrollment is recorded as 15, while the safety figures are presented in groups of 10 and 5. The record does not explain the relationship between these counts and the reported analysis populations, and no efficacy analysis is reported.
The arm descriptions pose an interpretive difficulty. The registry labels the study randomized, but describes one group as having serum ferritin ≥ 1,000 μg/l and receiving Exjade chelation, and another as having serum ferritin < 1,000 μg/l and not receiving the investigational product. How these definitions align with randomization is not reported. The threshold units are also inconsistent across the record: arm titles use μg/l, while arm descriptions use mg/L. No clarification is reported.
The record says that discontinuations led to missing assessments of iron exchange parameters and that protocol deviations affected efficacy assessment. It does not give reasons for discontinuation, timing of missing measurements, or a missing-data analysis. The stated Full Analysis Set description is truncated. No baseline outcome summaries or participant-level outcome trajectories are reported, and there is no primary efficacy estimate or measure of its precision.
Other study details that could inform interpretation, including eligibility criteria beyond the brief arm descriptions, randomization procedures, treatment adherence, and the statistical analysis plan, are not reported in the registry record. The safety entries lack event terms for serious adverse events and do not provide a broader account of adverse event severity or timing. These gaps mean the registry supports description of the intended question and selected safety counts, but not a firm efficacy or comparative safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients — NCT01818726.
- Registry record last updated 2019-08-16; status last verified 2019-07.
- Results first posted 2019-08-16.
- 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
NCT01818726 is a Phase 4, randomized, open-label, parallel-group study sponsored by Novartis Pharmaceuticals. It concerns Exjade (deferasirox) chelation for transfusion-dependent iron overload in adults with aplastic anemia receiving cyclosporine A. The registry records enrollment as 15, a start date of 2014-06-23, a primary completion date of 2016-10-17, and status as terminated.
The primary endpoint is change in serum ferritin, with descriptive summaries planned from Screening through Week 52. The registry states that efficacy analyses were not performed because of discontinuations, missing assessments, and protocol deviations affecting efficacy assessment. It reports no numerical primary efficacy result. Serious adverse event counts and deaths are listed as 0 in both ferritin-defined groups; other adverse event counts are 4 and 0. The arm descriptions use different ferritin categories and treatment exposure, and the registry does not clarify how these relate to the randomized designation.