Imaging Kidney Transplant Rejection Using Ferumoxytol-Enhanced Magnetic Resonance: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Imaging Kidney Transplant Rejection Using Ferumoxytol-Enhanced Magnetic Resonance (NCT02006108), a na na study. The primary outcome is Radiologically Detectable Differences in Signal Intensity Between Healthy and Rejected Kidneys, Measured Using T2* Maps.

2. Clinical Question

3. Trial Design

This is a completed, single-group study sponsored by Stanford University. The registry lists an enrollment of 21 and identifies renal transplant rejection as the condition under study. The study started on 2012-11-27, had a primary completion date of 2017-04-11, and is listed as completed. Its phase is recorded as NA.

Participants received intravenous Feraheme, described as 5 mg Fe/kg, and underwent an MR scan using a GE Healthcare 3 Tesla magnet. The registry lists masking as none and allocation as NA. It does not describe a randomized allocation process or a conventional treatment-control comparison. The stated scientific question contrasts signal in healthy and rejected kidneys, but that contrast should not be mistaken for evidence that participants were assigned to separate study arms.

The study's stated purpose was to develop a non-invasive imaging test for detecting kidney transplant rejection in vivo. Its hypotheses concerned whether ferumoxytol-MRI could estimate tissue iron and macrophages and whether renal allograft signal differed between rejected and non-rejected transplants. A secondary outcome concerns correlation between cell-bound iron quantities on QSM sequences and macrophage and iron stains on histopathology.

The registry record does not report the recruitment process, detailed eligibility criteria, number of kidneys assessed, procedures for assigning kidney status, or the timing of individual scans beyond the primary outcome timeframe. It also does not report a protocol-level statistical analysis plan or the actual primary outcome analysis. Therefore, the design can be described from the registered study characteristics, but the record does not support conclusions about how the planned diagnostic comparisons were carried out.

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

Analysis population for the primary outcome, as defined in the registry: T2\* value of transplant kidney

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 Radiologically Detectable Differences in Signal Intensity Between Healthy and Rejected Kidneys, Measured Using T2* Maps, measured over 24 hours to 7 days.

The primary endpoint is the mean T2* value of the transplant kidney, measured in milliseconds on delayed postcontrast scans. The stated measurement timeframe is 24 hours to 7 days. T2* maps provide a semiquantitative measure of MRI signal behavior, which the study uses to assess whether ferumoxytol-associated iron uptake is reflected in differences between healthy and rejected kidney tissue.

The biological rationale in the registry is that macrophage infiltration may be greater in rejected kidneys. Because macrophages are expected to take up injected iron, the resulting tissue iron may produce a detectable change in signal intensity. A difference in T2* could therefore be a candidate imaging feature for distinguishing kidney status. This is the proposed rationale, not a reported finding.

The registered outcome specifies a mean and standard deviation, but the registry record does not report the mean T2* values, their variability, a between-status contrast, or an estimate of diagnostic accuracy. It also does not report a threshold for classifying a kidney as rejected or healthy. Without those results and details, the endpoint definition explains what was intended to be measured but does not establish whether the measurement separated the groups or how precisely any separation was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary measure is continuous: a T2* value in milliseconds. For a continuous outcome, a mean describes the central value of observations, while a standard deviation describes how spread out those observations are around the mean. Together they can help readers understand both the typical measurement and the variability among measurements. They do not, by themselves, show whether two groups differ, and they do not show how precisely a group mean or a contrast has been estimated.

What would a comparison estimate?

To answer the stated question, an analysis would need to compare T2* measurements associated with healthy and rejected kidneys. A contrast between group means would describe the size and direction of the average difference on the measurement scale. A confidence interval around that contrast would communicate statistical uncertainty: narrower intervals indicate greater precision, while wider intervals indicate less precision. The registry record does not report a contrast or confidence interval, so neither the magnitude nor precision of a difference can be assessed.

A p-value, if reported, would address how compatible the observed data are with a specified null hypothesis under the assumptions of the test. It would not measure the probability that the hypothesis is true, and it would not establish clinical importance. No p-value or inferential test for the primary outcome is reported in the registry record. Nor does the record describe a test, model, or adjustment strategy for the primary comparison.

Why can variation matter?

Measurements may vary across kidneys because of biological differences, measurement conditions, or other sources of variability. When the spread of observations is substantial relative to a group difference, the estimate may be less precise. Some count outcomes can also show over-dispersion, meaning their variability is greater than a simple model expects; that can affect standard errors and uncertainty estimates. The primary endpoint in this study is continuous rather than a count, and the registry record does not report an over-dispersion assessment or a model for the T2* data. These are general statistical considerations, not claims about the study's observed data.

The secondary outcome concerns correlation between cell-bound iron quantities on QSM sequences and macrophage and iron stains on histopathology. Correlation describes the direction and strength of a pattern of association; it does not demonstrate that one measure caused the other, and it is not a direct measure of diagnostic accuracy. The registry lists the outcome but reports no correlation estimate, uncertainty interval, or analysis method. It also does not say whether the relationship was planned as exploratory or confirmatory.

What do the planning assumptions mean?

The registry gives assumptions for planning illustrations based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. These assumptions describe a hypothetical calculation framework; they do not establish the design of the completed study. In particular, the study itself is registered as single-group, not as an equal-allocation, randomized two-arm comparison. The registry record does not report the planning results or the fractions used in the illustrations.

A sample-size calculation asks how much information might be needed under specified assumptions to detect a target effect with a chosen level of statistical sensitivity. It is a planning exercise, not a result. A calculation based on an effect observed in the study must not be described as observed power, because observed power does not replace direct reporting of the estimated effect and its uncertainty. The registry's planning material is therefore best understood as illustrative rather than as evidence of the study's achieved precision.

For any statistical method to be fully evaluated, readers would need enough information about the analyzed population, outcome handling, model or test, missing observations, and uncertainty estimation. Those details are not reported in the registry record. General statistical concepts explain what such analyses could mean, but they cannot fill in the missing study-specific methods or results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures, including the primary T2* outcome and a secondary outcome concerning the correlation of cell-bound iron quantities on QSM sequences with macrophage and iron stains on histopathology. It reports no analyses. The record does not describe whether additional outcomes or comparisons were assessed, how many tests were conducted, or whether any approach was used to account for multiple testing. A multiplicity adjustment or a prespecified hierarchy of outcomes is therefore not reported in the registry record.

The registry also does not report how missing outcome measurements were handled, whether any observations were excluded, or whether all enrolled participants contributed to each analysis. The analysis population and the number of evaluable measurements for the primary endpoint are not reported in the registry record. Without this information, the completeness of the endpoint data and the potential influence of missingness cannot be assessed.

These gaps do not establish that outcomes were missing or that multiple testing occurred. They mean that the registry record does not document the relevant procedures. Any interpretation of the primary or secondary findings would require the analysis results and methods, including how outcome data and multiple comparisons were handled.

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 0% reporting threshold.

The registry's adverse-event entry lists the Feraheme group with 21 participants at risk for serious adverse events and zero affected. It also lists 21 at risk for other adverse events and zero affected, with deaths recorded as 0. These are the counts recorded in the registry for that group; they are not estimates of the probability of an event beyond this study.

Zero recorded events in a study does not establish that an event cannot occur, and it does not show that the intervention is free of risk. Event counts are interpreted in light of the number at risk, the duration and completeness of safety monitoring, the definitions used, and the accuracy of event reporting. The registry record does not describe those monitoring procedures or provide a detailed adverse-event listing.

The safety figures should therefore be read narrowly: the registry reports no serious adverse events, other adverse events, or deaths for the recorded group. The record does not provide enough detail to evaluate event ascertainment, timing, severity categories beyond the listed groupings, or comparisons with another group. There is no like-for-like control comparison in this single-group study.

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

This study addresses whether ferumoxytol-enhanced MRI could provide a non-invasive signal related to kidney transplant rejection. Its registered primary endpoint, mean T2* on delayed postcontrast scans, connects the imaging measurement to the proposed mechanism of iron uptake by macrophages. That makes the question relevant to imaging research, but a plausible mechanism is not equivalent to a demonstrated diagnostic result.

The registry record does not report the primary outcome values, the difference between healthy and rejected kidneys, or uncertainty around any difference. It therefore cannot show whether the signal differed, how large a difference may have been, or whether the measurements were sufficiently precise to distinguish kidney status. It also cannot establish diagnostic accuracy or whether using the imaging measurement would change clinical decisions.

The registered secondary relationship between QSM cell-bound iron quantities and histopathology stains could provide information about how an imaging measure relates to tissue findings. However, no analysis for that outcome is reported in the registry record. Even a correlation, in general, would describe association rather than prove causation or establish that an imaging test correctly classifies individual kidneys.

The single-group design, no masking, and absence of a registered randomized control comparison also limit what can be inferred about comparative effects. The contrast between healthy and rejected kidneys is the scientific question, not evidence of a randomized intervention effect. The registry does not report enough detail about kidney classification or the analysis procedures to resolve those interpretive issues.

In short, the record establishes the study's aim, intervention, and intended endpoint, but not the evidence needed to judge whether the imaging hypothesis was supported. The lack of reported results is not a negative finding; it is an absence of evaluable outcome information in the registry record.

13. Why This Trial Matters Statistically

The statistical importance of this study lies in the gap between a well-defined measurement question and the information needed to assess it. The registry identifies a continuous MRI endpoint, a biological rationale, and a time window for measurement. Those features make the intended analysis understandable: assess whether T2* measurements differ in association with healthy versus rejected kidney status.

For a diagnostic imaging question, an average difference is only one part of the evidence. Readers also need to know the spread of measurements, the uncertainty around any contrast, and how much the distributions overlap. A difference in group means alone would not necessarily show that individual kidneys could be classified accurately. Measures of diagnostic performance and details about the reference classification would be needed to address that separate question. The registry record does not report those results or details.

The study also illustrates why design and analysis descriptions should be read together. The scientific hypothesis refers to two kidney states, while the registered design is single-group and not masked. The planning assumptions describe equal allocation between two arms, but that planning framework does not convert the registered study into a randomized two-arm comparison. Clear reporting is needed to distinguish a biological or diagnostic contrast from a randomized treatment comparison.

Finally, a completed status does not by itself communicate the findings. Without the primary analysis, uncertainty estimates, and outcome-handling methods, readers cannot judge effect size, precision, or robustness. The registry record is informative about the intended research question, but it does not supply the results necessary to evaluate its statistical answer.

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 interpretation is that no primary endpoint results or analyses are reported in the registry record. The mean T2* measurements, standard deviations, comparison between kidney states, and uncertainty estimates are all absent. The stated hypothesis therefore cannot be evaluated from the registry entry.

The record does not explain how healthy and rejected kidney status was determined, how many kidneys contributed measurements, or whether classification was made independently of imaging. Those details are particularly relevant for a diagnostic imaging study because they affect interpretation of any apparent separation between groups. The registry also does not report a diagnostic threshold or performance measures.

Masking is listed as none. The record does not describe whether image assessment, histopathology assessment, or kidney-status classification was blinded in any other way. It does not provide details of recruitment, eligibility, missing measurements, exclusions, or analysis populations. These omissions prevent a full assessment of selection, measurement, and analysis processes.

The study is registered as single-group, with no like-for-like control comparison. Its planning assumptions refer to equal allocation between two arms, but the registry does not report the actual planning outputs or explain how they relate to the registered design. The record also gives no protocol-level account of the statistical methods, multiplicity handling, or treatment of missing data. These limitations describe what cannot be evaluated from the registry record; they do not establish that a particular bias or analytical problem occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Imaging Kidney Transplant Rejection Using Ferumoxytol-Enhanced Magnetic Resonance — NCT02006108.
• Registry record last updated 2018-05-11; status last verified 2018-04.
• Results first posted 2017-06-27.
• 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

NCT02006108 is a completed, single-group study sponsored by Stanford University, with an enrollment of 21 and a focus on renal transplant rejection. Participants received intravenous Feraheme, described as 5 mg Fe/kg, and underwent MRI using a GE Healthcare 3 Tesla magnet. Masking is listed as none, and allocation as NA.

The primary endpoint is mean T2* value of a transplant kidney, measured in milliseconds on delayed postcontrast scans during 24 hours to 7 days. The stated hypothesis is that iron uptake associated with macrophage infiltration may produce a signal difference between healthy and rejected kidneys. A secondary outcome concerns correlation of cell-bound iron quantities on QSM sequences with macrophage and iron stains on histopathology.

The registry lists zero serious adverse events, zero other adverse events, and deaths of 0 for the Feraheme group. It does not report primary or secondary analyses, endpoint values, or statistical uncertainty. Thus, the study's registered question and design are described, but its imaging results cannot be evaluated from the registry record.