Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload (NCT01254227), a na phase 2 study. The primary outcome is Change in Cardiac Iron Content From Baseline to Month 12.

2. Clinical Question

The study’s primary focus was change in cardiac iron content from baseline to Month 12. Cardiac T2* is described in the registry record as a sensitive and reproducible test for detecting myocardial iron load. A value <10 ms is defined there as severe cardiac iron overload.

The clinical question is framed as a before-and-after assessment in one treated group, rather than a comparison of two randomized groups. That framing matters: a change over time can describe what occurred during the study, but without a concurrent control group it cannot by itself separate the intervention’s contribution from other influences, such as changes over time or participant characteristics.

The registry record also lists secondary questions concerning T2* status and change at other follow-up points, cardiac iron concentration, and left and right ventricular ejection fraction. These are additional outcomes, not substitutes for the stated primary endpoint. Numerical results for the primary endpoint are not reported in the registry record.

3. Trial Design

This is a phase II, open-label, multicenter, single-group study. The registry record gives an enrollment of 60 and describes the intervention as deferasirox combined with deferoxamine, followed by deferasirox monotherapy. It lists no randomized allocation and no masking. The study status is completed.

The design has no concurrent control arm. The primary endpoint is a change from baseline to Month 12, so the central comparison is within participants over time. Such a design can describe the observed trajectory in the enrolled group, but it does not create a like-for-like comparison with people who did not receive the study intervention. The registry record itself cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison.

The registry record lists the study start as 2011-01 and primary completion as 2013-11. The primary endpoint timeframe is baseline to Month 12. Secondary outcome descriptions include assessments at Month 6, Month 12, Month 18, and Month 24, depending on the outcome. The record does not give additional operational details about visit windows or treatment duration.

Open-label means masking was not used, as indicated in the record. In general, lack of masking can matter when outcomes or decisions involve judgment, although the primary endpoint is described as an imaging-based measure. The registry record does not detail image-reading procedures or whether assessors were otherwise blinded.

The record identifies the sponsor as Novartis Pharmaceuticals. It does not report a protocol rationale for the sample size, a sample-size justification, or details of interim analyses. Those design features should not be inferred from the phase, enrollment, or completion status.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total 60 participants were enrolled in the study of which 34 completed the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set includes all participants to whom study treatment had assigned. Participants were considered evaluable for the efficacy endpoint if they had received at least one dose of study treatment and had baseline and a post baseline assessment prior to or on the time of the assessment of the corresponding efficacy endpoint.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Cardiac Iron Content From Baseline to Month 12, measured over From Baseline to Month 12.

The primary endpoint is change in cardiac iron content from baseline to Month 12, expressed using a geometric mean and a 95% confidence interval. The registry describes cardiac T2* as the measurement used to assess myocardial iron load, and defines a cardiac T2* value <10 ms as severe cardiac iron overload.

In general, T2* is an imaging measure used to characterize iron-related effects in the heart; the registry record specifically notes its sensitivity and reproducibility for detecting myocardial iron load. Assessing change from baseline allows each participant’s follow-up measurement to be considered in relation to their own starting measurement. That is a within-participant comparison, not a comparison against an untreated or usual-care group.

A geometric mean is a summary suited to positive measurements whose variation is more naturally understood on a multiplicative scale. In general, it describes a typical level after accounting for multiplicative rather than additive differences. The registry record identifies the endpoint parameter and its confidence interval, but does not report the numerical estimate, confidence limits, or detailed calculation method.

The endpoint description says participants without a baseline T2* measurement or without any post-baseline T2* measurement are excluded from the analysis. It also describes an efficacy population requiring at least one dose of study treatment and baseline and post-baseline assessment. The final wording of that population description is incomplete in the registry record, so further eligibility details cannot be established from it.

The endpoint is clinically focused on cardiac iron, but no numerical result for the baseline-to-Month-12 change is reported in the registry record. Its direction and precision therefore cannot be characterized from the registry information available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a geometric mean for the primary endpoint and a 95% confidence interval. It does not report the numerical estimate, the interval limits, or a detailed statistical analysis plan. The explanations below describe general statistical concepts; they do not imply that a particular unreported procedure was used in this study.

What does a geometric mean describe?

In general, a geometric mean summarizes positive measurements on a multiplicative scale. It is calculated by taking the arithmetic mean of logarithmically transformed values and transforming that summary back to the original scale. This can be useful when variation is proportional: a change that is similar in relative size across participants may be more meaningful than a constant absolute difference. The registry record names the geometric mean as the endpoint parameter, but does not specify the exact transformation, model, or calculation used for the reported change.

Because the endpoint is described as change from baseline, baseline and follow-up measurements are related within each participant. In general, an analysis of repeated measurements should account for this relationship rather than treat the two measurements as independent observations. The registry record does not state which model or estimation procedure was used to handle the paired measurements.

How should a confidence interval be read?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the method used. A narrower interval indicates greater precision than a wider interval for the same quantity and method. The interval does not by itself resolve whether an observed change is attributable to the intervention, particularly in a single-group study without a concurrent control. The registry record specifies a 95% confidence interval for the primary endpoint but does not report its bounds, so its precision cannot be judged.

A confidence interval is also not a guarantee that the true value falls inside the particular reported interval. In general, its interpretation comes from the long-run properties of the procedure used to construct intervals under its assumptions. Those assumptions and the endpoint estimate are not detailed in the registry record.

What does the single-group comparison estimate?

In general, comparing follow-up with baseline in one group describes change over time among the participants included in the analysis. It does not directly estimate a treatment effect relative to a control group. A concurrent randomized comparator helps distinguish differences associated with assigned treatment from other changes that occur over time. This study is listed as single-group, with no randomized allocation or masking, so its design does not provide that type of between-group contrast.

The primary endpoint uses cardiac T2* as a measure of cardiac iron content. The record states that values <10 ms define severe cardiac iron overload and describes the test as sensitive and reproducible for detecting myocardial iron load. These measurement properties support the endpoint’s stated rationale, but they do not replace the need to report the actual estimate and its uncertainty.

What do the planning assumptions mean?

The registry record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. The record distinguishes total events for time-to-event illustrations from participants per arm for other illustrations.

These assumptions describe a planning exercise, not the trial’s actual design. In particular, a two-arm equal-allocation illustration should not be mistaken for evidence that this single-group study randomized participants between two arms. The record does not report a trial-specific sample-size justification or the observed effect and resulting planning counts in the information available. Planning sample sizes are not observed power. In general, power calculated after a study from an observed effect does not add evidence beyond the effect estimate and its uncertainty.

The two-sided significance level is a general convention for assessing departures in either direction under a specified test. The record’s planning assumptions mention that level, but do not establish that the primary endpoint was tested using a particular hypothesis test. The statistical test, any model covariates, handling of repeated assessments, and prespecified decision threshold for the efficacy analysis are not reported in the registry record.

Why does analysis-population definition matter?

In general, an analysis population determines which participants contribute to an estimate and can affect both the estimate and its precision. The record describes a Full Analysis Set as including all participants to whom study treatment had been assigned. It also says endpoint-evaluable participants had received at least one dose and had baseline and post-baseline assessment. The description is incomplete at its end, so the full evaluability rule is not available.

The endpoint description explicitly excludes participants without baseline T2* or any post-baseline T2*. Excluding participants with missing measurements can be consequential if the reasons for missingness are related to their outcomes. The record does not report how many measurements were missing, why they were missing, or whether any imputation or sensitivity analysis was used. General statistical practice distinguishes a complete-measurement analysis from methods that model or impute missing values; no specific approach should be assumed.

Finally, interpreting multiple outcomes requires knowing which analyses were planned, how they were ordered, and whether adjustments were used to control the risk of false-positive findings across tests. The record lists seven outcome measures and zero analyses, but does not report an adjustment strategy or detailed inferential results. This leaves the statistical evidence across the full set of outcomes uncharacterized.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven outcome measures, including the primary endpoint and secondary measures of T2*, cardiac iron content, left ventricular ejection fraction, right ventricular ejection fraction, and cardiac iron concentration. Several secondary outcomes are assessed at multiple follow-up points. Considering multiple outcomes or time points can raise a multiplicity issue: in general, the chance of at least one false-positive result can increase when many inferential tests are conducted.

The record reports zero analyses and does not describe a multiplicity adjustment, a hierarchy of testing, or a prespecified strategy for interpreting secondary outcomes. These statistical details are not reported in the registry record. Numerical estimates and inferential results for the secondary outcomes are also not reported, so the degree to which outcomes agree cannot be assessed.

For the primary endpoint, participants without baseline T2* or any post-baseline T2* are described as excluded. The efficacy-population description also requires at least one dose and baseline and post-baseline assessment, but its final wording is incomplete. The record does not report the number of participants excluded under these criteria, the extent or reasons for missing measurements, or a missing-data method. It does not report whether sensitivity analyses assessed the effect of missingness.

In general, missing-data methods rely on assumptions about why observations are absent. Without the amount and pattern of missingness, and without a stated method, the robustness of the endpoint analysis to incomplete follow-up cannot be evaluated from the registry record.

11. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (3.3%), anaemia (1.7%), dermoid cyst (1.7%), irritable bowel syndrome (1.7%), pancreatitis acute (1.7%).

Safety counts are reported for all participants, with 60 at risk for serious adverse events and 60 at risk for other adverse events. The serious-event affected count is 17; the other-event affected count is 52. The registry record also reports 1 death. These are counts recorded for this study group, not comparisons between treatment groups.

The serious-event terms listed include abdominal pain (3.3%), anaemia (1.7%), dermoid cyst (1.7%), irritable bowel syndrome (1.7%), pancreatitis acute (1.7%), and reflux gastritis (1.7%). These percentages are reproduced as reported. The record does not provide further detail about event timing, severity grading, recurrence, or the relationship of each event to study treatment.

In general, an affected-participant count is different from a count of all event occurrences when one participant can experience more than one event. The registry record labels affected participants and provides event terms, but does not give enough detail to interpret each term as a unique participant count or as the total number of occurrences. The counts should therefore be read as descriptive registry safety information, not as a causal comparison or a rate adjusted for follow-up time.

The death count is reported without additional attribution details in the available record. A death occurring during a study does not, by itself, establish that the study intervention caused it. The single-group design also provides no concurrent safety comparator.

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

The registry record establishes that this was a phase II, open-label, single-group study of deferasirox with deferoxamine followed by deferasirox monotherapy in patients with severe cardiac iron overload due to chronic blood transfusion. It defines the primary endpoint as change in cardiac iron content from baseline to Month 12, using a geometric mean and a 95% confidence interval. It also states how cardiac T2* relates to the endpoint and identifies a threshold used to define severe cardiac iron overload.

Those details explain the question the study was designed to address, but they are not a numerical efficacy result. The registry record does not report the primary estimate or its confidence interval. It therefore does not show the magnitude or direction of change, nor how precisely that change was estimated. Results for the listed secondary outcomes are also not reported in the registry record.

Even if a before-and-after change were available, the single-group design would limit causal interpretation. In general, participants may change over time for reasons other than the intervention. A control group can help distinguish those influences from differences associated with assigned treatment; this study has no randomized comparator. The study’s design can describe outcomes in the group studied, but it cannot provide a like-for-like controlled treatment contrast.

The safety information records serious events, other events, and a death among participants in the study group. These observations are important descriptive information, but they do not establish causation or comparative safety. The record does not provide the detail needed to assess event timing or attribution for the listed terms.

Accordingly, the registry record supports a description of the trial’s design, endpoint definitions, analysis-population language, and selected safety counts. It does not support a quantitative conclusion about the primary endpoint or a controlled estimate of treatment effect.

13. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and study design must be read together. Cardiac T2* is identified as the measure for assessing myocardial iron load, and the registry record defines <10 ms as severe cardiac iron overload. The primary endpoint is framed as a change from baseline to Month 12, giving a clear clinical measurement target. But an endpoint definition is not itself evidence about the size or precision of a result; the registry record does not report the numerical primary estimate or its confidence interval.

The single-group structure is statistically important. A within-participant baseline comparison can describe change in the enrolled group, while a randomized concurrent control is needed for a direct comparative estimate protected against many time-related differences. Recognizing that distinction prevents an observed change, if reported, from being mistaken for a controlled treatment effect.

The record also demonstrates the importance of analysis populations and missing measurements. It says participants lacking a baseline or post-baseline T2* are excluded, and gives a further efficacy-population description that is incomplete. Without the number and pattern of excluded measurements, or a stated missing-data approach, readers cannot assess how representative the analyzed group may be of all enrolled participants.

Finally, the record lists multiple outcome measures and follow-up points but no analyses. In general, interpreting many outcomes calls for attention to multiplicity and the prespecified testing strategy. Those details, together with the numerical efficacy findings, are not reported in the registry record. The safety counts remain useful as descriptive observations, but the absence of a comparator limits their comparative interpretation as well.

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 primary limitation for statistical interpretation is that the registry record does not report the primary endpoint estimate or its 95% confidence interval. It also does not report numerical results for the secondary outcomes. As a result, the magnitude, direction, precision, and consistency of efficacy findings cannot be evaluated from the record.

The study is single-group and has no randomized comparator. A change from baseline can describe the observed course among participants, but cannot isolate the intervention’s effect from other changes over time. The open-label design adds another limitation; the registry record does not describe any procedures used to mask measurement assessors or reduce assessment bias.

The endpoint description excludes participants without baseline or post-baseline T2*. The number of participants excluded, the extent and reasons for missing data, and any imputation or sensitivity analyses are not reported in the registry record. The stated Full Analysis Set and evaluability descriptions are incomplete or insufficiently detailed to resolve all analysis-population questions.

The record lists multiple outcomes and time points, but does not report a multiplicity strategy or analyses. It also does not report the specific statistical model, test, covariate adjustments, or sample-size justification. A planning illustration is described using an observed effect and assumptions for two-arm calculations, but the observed effect and resulting planning counts are not reported in the registry record. That illustration is not the same as the design of this single-group trial and is not observed power.

Safety information is descriptive and lacks a concurrent comparator and further event attribution details. These limitations constrain interpretation; they do not establish that an unreported result was favorable or unfavorable.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload — NCT01254227.
• Registry record last updated 2021-07-26; status last verified 2021-07.
• Results first posted 2021-06-24.
• 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.

18. Record Summary

The registry record describes a completed phase II, open-label, multicenter, single-group study with an enrollment of 60. The intervention was deferasirox combined with deferoxamine followed by deferasirox monotherapy. The primary endpoint was change in cardiac iron content from baseline to Month 12, assessed using cardiac T2* and summarized as a geometric mean with a 95% confidence interval.

The record defines a cardiac T2* value <10 ms as severe cardiac iron overload. It lists seven outcome measures and no analyses. The numerical primary endpoint estimate, confidence interval, and secondary outcome results are not reported in the registry record. The analysis-population description excludes participants without baseline or post-baseline T2*, while further details on missingness and analysis methods are not reported.

Safety information includes 17 participants in the serious-event affected count, 52 in the other-event affected count, and 1 death, with 60 at risk in each category. The single-group design supports descriptive interpretation, not a randomized comparison.