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 Study to Evaluate Vadadustat for Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) Who Are Hyporesponsive to Erythropoiesis Stimulating Agents (NCT03140722), a randomized phase 2 study. The primary outcome is Change From Baseline in Hemoglobin (Hb) Over Time During the Treatment Period.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03140722 |
| Phase | Phase 2 |
| Condition | Anemia, Dialysis-Dependent Chronic Kidney Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Akebia Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
People with anemia and dialysis-dependent chronic kidney disease who were hyporesponsive to erythropoiesis stimulating agents. The registry record describes the intended population; it does not provide participant-level characteristics.
Intervention
Vadadustat, administered as a daily oral dose adjustable based on hemoglobin level.
Comparator
Epoetin alfa, with its dose adjustable based on hemoglobin level as clinically indicated throughout the study.
Primary question
How did hemoglobin change from baseline over time during the treatment period in this randomized comparison? The planned timeframe was baseline through up to 20 weeks, but no efficacy analysis or participant-level result is reported.
The study was intended to evaluate vadadustat against epoetin alfa in a population specifically described as hyporesponsive to erythropoiesis stimulating agents. Its primary endpoint focused on change in hemoglobin over time, rather than a single endpoint value. The record also lists outcomes concerning hemoglobin levels, rescue treatment, transfusion, iron use, biomarkers, and resource use. These registered outcomes indicate several aspects the study intended to assess, but they do not establish that those assessments produced interpretable comparative results.
The registry reports enrollment of N=2 and states that efficacy analyses were not conducted because of the limited number of participants enrolled before termination. It also states that enrolled participants’ results cannot be reported to protect their privacy. Consequently, the clinical question remains unanswered by the efficacy results in the registry record: there is no reported estimate of hemoglobin change for either treatment, no comparison between treatment groups, and no reported uncertainty interval for a treatment difference.
3. Trial Design
This was a Phase 2, randomized, open-label study with a parallel-group model. It planned to compare vadadustat with epoetin alfa for anemia in people with dialysis-dependent chronic kidney disease who were hyporesponsive to erythropoiesis stimulating agents. The study is listed as terminated. The registry reports enrollment of N=2 and says no efficacy analyses were conducted because the number enrolled before termination was limited.
The interventions were both drugs. Vadadustat was described as a daily oral dose adjustable based on hemoglobin level. Epoetin alfa was described as dose-adjustable based on hemoglobin level, as clinically indicated throughout the study. The record does not give further details about dose schedules, treatment adherence, or how treatment adjustments were implemented.
Randomization is part of the registered design, but the record does not report the allocation sequence, allocation concealment, or the number assigned to each arm. The study had no masking. In an open-label design, treatment assignment is not concealed from participants or study staff; this can matter for outcomes involving judgment or decisions about care, even when an outcome is measured objectively. The record does not describe specific safeguards against those influences.
The primary endpoint was change from baseline in hemoglobin over time during the treatment period, with a timeframe of baseline through up to 20 weeks. The registry also lists secondary outcomes involving hemoglobin patterns and target-range values, epoetin alfa rescue, red blood cell transfusion, biomarkers, intravenous elemental iron, iron sufficiency, and resource use. Although ten outcome measures are listed, the record does not provide efficacy results for these measures. It also does not report a detailed statistical analysis plan or the reason for terminating the study.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Vadadustat | Epoetin Alfa |
|---|---|---|
| STARTED | 0 | 2 |
| COMPLETED | 0 | 2 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
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: All subjects enrolled in the trial.
| Characteristic | Unit | Vadadustat | Epoetin Alfa | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 2 | 2 | |
| Age, Categorical: <=18 years | Participants | — | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | — | 1 | 1 |
| Age, Categorical: >=65 years | Participants | — | 1 | 1 |
| Sex: Female, Male: Female | Participants | — | NA | NA |
| Sex: Female, Male: Male | Participants | — | NA | NA |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | — | NA | NA |
| Race (NIH/OMB): Asian | Participants | — | NA | NA |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | — | NA | NA |
| Race (NIH/OMB): Black or African American | Participants | — | NA | NA |
| Race (NIH/OMB): White | Participants | — | NA | NA |
| Race (NIH/OMB): More than one race | Participants | — | NA | NA |
| Race (NIH/OMB): Unknown or Not Reported | Participants | — | NA | NA |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Hemoglobin (Hb) Over Time During the Treatment Period, measured over Baseline; up to 20 weeks.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change from baseline in hemoglobin (Hb) over time during the treatment period. The registered timeframe was baseline through up to 20 weeks. Hemoglobin is a measured blood component, and tracking its change over time provides a way to describe how its level develops during treatment rather than relying only on a value at one time point. The endpoint therefore concerns both the direction and pattern of change, although the registry record does not report a definition of the planned summary measure or the analysis used to characterize that pattern.
As a general statistical consideration, a repeated-measure outcome can contain information about measurements across the follow-up period. Its interpretation depends on which time points are included, how measurements are summarized, and how incomplete follow-up is handled. These details are not reported in the registry record. The record gives the timeframe but does not provide the measurement schedule, a baseline definition, or a clinically meaningful threshold for change.
The endpoint is relevant to the stated study question because the trial aimed to compare two treatments for anemia in people with dialysis-dependent chronic kidney disease who were hyporesponsive to erythropoiesis stimulating agents. However, no efficacy analysis was conducted, and participant results cannot be reported for privacy. There is therefore no posted estimate of change in hemoglobin, no treatment contrast, and no indication of how precisely any such contrast could have been estimated. The endpoint definition describes what the study intended to measure, not a finding about either treatment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the registry does not report efficacy findings. It states that no efficacy analyses were conducted because only N=2 participants had enrolled before the study was terminated. It further states that results for enrolled participants cannot be reported in order to protect their privacy. Thus, the registry record supplies no analyzed hemoglobin changes, no between-group estimate, and no confidence interval or other measure of uncertainty for the primary endpoint.
This absence of an efficacy estimate is different from a result showing little or no difference. A comparison requires reported outcome data and an analysis; neither is available in the efficacy record. It is therefore not possible to determine from the posted results whether hemoglobin changed in either arm, whether changes differed between arms, or how compatible the data might be with different possible treatment effects. No conclusion about efficacy follows from the lack of a reported analysis.
The trial’s randomized, parallel design describes how a comparative study was intended to work. Random assignment can, in a sufficiently informative trial, support a comparison by reducing systematic differences between treatment groups. In this record, however, the very limited enrollment and privacy restriction prevent an efficacy comparison from being reported. Randomization alone does not supply an estimate or resolve uncertainty when outcome results are unavailable.
The registry lists secondary outcomes, including participants with incremental hemoglobin increases, values within the target range of 10.0-11.0 g/dL, epoetin alfa rescue, red blood cell transfusion, specified biomarker levels, intravenous elemental iron dose, iron sufficiency, and resource use. These are planned or registered outcome topics, not reported findings. The record does not support conclusions about any of them.
The safety figures also need cautious interpretation. The adverse-event record lists zero participants at risk and zero affected for the vadadustat group, while the epoetin alfa group lists two at risk and zero affected for both serious and other adverse events, with zero deaths. The vadadustat entries do not provide an exposed denominator from which to assess observed risk. The small amount of safety information cannot establish that either treatment is safe or unsafe.
Overall, this record documents a terminated randomized study with no reportable efficacy analysis. Its design and endpoint explain the question the investigators intended to address; they do not answer that question. Any planning quantities based on an observed effect should also be interpreted cautiously: the registry does not report an efficacy effect estimate, and a planning illustration is not an observed treatment result.
9. Statistical Methods Explained
What does randomization contribute?
In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the start of a trial, including differences that may not have been measured. When outcomes are available and the study is sufficiently informative, a randomized comparison can support an estimate of the effect of assignment to one treatment rather than another. The registry identifies this study as randomized, but it does not report the allocation procedure or arm-specific enrollment. Because efficacy analyses were not conducted and participant results are withheld for privacy, randomization does not yield a reported treatment-effect estimate in this record.
What does the open-label design mean?
Open-label means treatment assignment is not masked from participants and study personnel. In general, knowledge of assignment may influence behavior, co-interventions, clinical decisions, or reporting of outcomes. Hemoglobin is a measured laboratory outcome, but decisions such as rescue treatment or dose adjustment can involve clinical judgment. The record says doses could be adjusted based on hemoglobin level and, for epoetin alfa, as clinically indicated. It does not describe procedures for standardizing adjustments or limiting possible influence of treatment knowledge. These are design considerations, not evidence that bias occurred.
How should change over time be understood?
A repeated-measure endpoint describes measurements collected over follow-up. In general, analysis may estimate change at selected time points, an average pattern, or another summary across time. The choice affects the meaning of the result. The registry specifies change from baseline in hemoglobin over time and a timeframe of baseline through up to 20 weeks, but it does not report which summary was planned or how measurements were to be modeled. Since no efficacy analysis was conducted, there is no reported trajectory to interpret.
What does a confidence interval ordinarily tell a reader?
As a general concept, a confidence interval communicates the precision of an estimated quantity by describing a range of values compatible with the data under the model used. A narrow interval indicates greater precision than a wide interval, while an interval spanning materially different possibilities may leave substantial uncertainty. An interval is not a guarantee that the true effect lies within its endpoints. No confidence interval for the primary endpoint is reported in the registry record, so precision cannot be assessed for a treatment comparison.
Why does sample size matter?
In general, the amount of information in a trial affects how precisely it can estimate treatment differences and how readily it can distinguish a signal from random variation. A small enrollment can leave estimates highly uncertain, but the registry record does not report an efficacy estimate to quantify that uncertainty. It reports enrollment of N=2 and explains that no efficacy analyses were conducted, with participant results withheld for privacy.
The record’s planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Such assumptions describe a planning exercise, not the trial’s own design justification or an observed power calculation. The registry does not report a sample-size justification or the effect used for planning. Because no efficacy result is reported, a planning illustration must not be read as evidence that the study observed an effect or had a particular ability to detect one.
What is over-dispersion, in general?
For count outcomes, over-dispersion means the observed variation is greater than a simple statistical model expects. If it is ignored, standard errors can be too small and uncertainty can be understated. This is a general issue for some count-data analyses; the registry does not report a count-data model or an analysis of event counts for this study. The concept therefore explains a possible methodological concern, not a method confirmed to have been used.
What can be said about statistical testing?
A significance test, in general, evaluates how compatible data are with a specified null hypothesis under particular assumptions. A p-value does not express the probability that a treatment works, nor does it measure the clinical importance of an effect. There is no reported efficacy test or p-value for the primary endpoint. The significance level of 0.05 appears among the stated planning assumptions; it should not be mistaken for a reported analysis result or confirmed trial analysis plan.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and multiple secondary outcome topics. When a study tests or estimates several outcomes, multiplicity can arise: conducting many statistical tests can increase the chance of at least one apparently notable result by chance. General approaches include identifying a primary hypothesis in advance, adjusting tests, or treating secondary analyses as exploratory. The registry record does not report a multiplicity adjustment strategy, a testing hierarchy, or a detailed statistical analysis plan. No efficacy analyses were conducted, so there are no reported efficacy tests to interpret as a family of results.
The record does not describe how missing outcome measurements would have been handled, whether participants who discontinued treatment would remain in an analysis, or which analysis populations were planned. These details are not reported in the registry record. In general, missing-data methods can affect estimates when the reason data are missing is related to outcomes or treatment. Without an analysis plan or participant-level results, it is not possible to assess missingness or the impact of any method.
The registry’s statement that participant results cannot be reported to protect privacy is distinct from a conventional missing-data problem within an efficacy analysis. The record says that no efficacy analyses were conducted because of limited enrollment before termination; it does not supply aggregate efficacy estimates. The number of analyses is listed as zero. This does not establish what analyses might have been planned in a protocol or what would have been done had enrollment continued. Those details are not reported in the registry record.
Although the primary endpoint timeframe extends through up to 20 weeks, the record does not describe visit-level completeness or follow-up for individual participants. No inference about completion, attrition, or the pattern of missing measurements is justified from the reported information.
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 |
|---|---|---|---|
| Epoetin Alfa | 0 | 2 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Vadadustat | 0 of 0 |
| Epoetin Alfa | 0 of 2 |
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 |
|---|---|
| Vadadustat | 0 of 0 |
| Epoetin Alfa | 0 of 2 |
The registry separates serious adverse events from other adverse events and lists the number at risk and the number affected, along with deaths. For vadadustat, the record lists zero at risk and zero affected in both categories, with zero deaths. For epoetin alfa, it lists two at risk and zero affected for serious adverse events, and two at risk and zero affected for other adverse events; deaths are listed as zero.
The vadadustat entries require particular care: zero at risk is not an exposed group with observed zero events. It does not provide an at-risk denominator for interpreting event frequency. The epoetin alfa entries describe no affected participants among the two listed at risk, but that limited observation cannot characterize safety reliably or rule out uncommon or unobserved harms. The record does not provide event-level detail or follow-up time for interpreting these counts.
These figures are not a basis for comparing safety between treatments. They should be read as the limited adverse-event information recorded, not as evidence that either treatment is safe or unsafe. The study’s termination and limited enrollment further restrict what these figures can establish.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, open-label Phase 2 study was undertaken to evaluate vadadustat against epoetin alfa in people with anemia and dialysis-dependent chronic kidney disease who were hyporesponsive to erythropoiesis stimulating agents. It identifies change from baseline in hemoglobin over time as the primary endpoint and lists additional outcome areas. It also reports that the study was terminated after enrollment of N=2.
What the record does not establish is the comparative effect of the treatments. No efficacy analyses were conducted, and participant results cannot be reported to protect privacy. There is no reported hemoglobin result, treatment contrast, confidence interval, or efficacy test. The absence of these results should not be interpreted as evidence of no difference, evidence of equivalence, or evidence that either treatment changes hemoglobin in a particular way.
Likewise, the listed secondary outcomes do not constitute findings. The registry record does not provide results for hemoglobin target-range values, rescue treatment, transfusions, biomarkers, iron use, iron sufficiency, or resource use. The adverse-event counts are limited and do not support a comparative safety conclusion.
In general, a terminated study can still contribute useful information about feasibility or study conduct when those results are reported. This record does not provide enough information to assess why termination occurred or to draw broader conclusions about feasibility. It documents the intended design and the reason efficacy results are absent, but it does not resolve the clinical question the study was designed to examine. Interpretation should remain bounded by those limits.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a study design and an informative result. Randomization and a defined primary endpoint are important components of a comparative trial, but neither guarantees that the trial will produce an interpretable treatment estimate. Here, limited enrollment before termination meant efficacy analyses were not conducted, and privacy protection prevents participant-level results from being reported.
The distinction between no reported comparison and a reported comparison close to zero is essential. Without an estimate and a measure of uncertainty, readers cannot judge the range of effects compatible with the data. Nor can they evaluate whether the planned endpoint was measured consistently or how results might vary over the follow-up period. A registry record that documents the study question but lacks efficacy estimates cannot support a statistical conclusion about treatment differences.
The open-label design also highlights why statistical interpretation depends on more than a model or a p-value. Treatment adjustment and outcomes such as rescue treatment can involve clinical decisions; knowledge of assignment can matter to those processes. The registry describes dose adjustment but does not report detailed procedures for standardization. This does not demonstrate bias, but it identifies context that would be relevant when interpreting any reported comparison.
Finally, the record shows why planning illustrations should remain separate from observed findings. A sample-size illustration depends on assumptions and an effect used for planning; it does not turn an unavailable efficacy result into evidence or establish observed power. The registry’s stated planning assumptions are not a reported trial-specific sample-size justification. Keeping these distinctions clear prevents design details and safety counts from being mistaken for evidence answering the primary clinical question.
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 most consequential limitation is the absence of efficacy analyses. The registry attributes this to the limited enrollment before study termination and states that participant results cannot be reported to protect privacy. As a result, there is no primary endpoint estimate, treatment comparison, or reported uncertainty with which to assess the study question.
Enrollment was N=2, and the record does not report the allocation of participants between arms. It therefore does not support assumptions about the number assigned to either treatment. The adverse-event record lists zero at risk in the vadadustat group, which also limits interpretation of its event entries. The information is too limited to characterize comparative efficacy or safety.
The study was open-label, and dose adjustment was based on hemoglobin level; the epoetin alfa dose could also be adjusted as clinically indicated. The registry does not describe detailed procedures for dose adjustment, outcome measurement, or protection against possible influence of treatment knowledge. These omissions limit assessment of how consistently treatment was delivered and outcomes were evaluated, but they do not show that a particular bias occurred.
Several analytic details are not reported in the registry record, including the planned statistical model, definition of the summary measure for change over time, handling of missing measurements, analysis populations, multiplicity strategy, and sample-size justification. The reason for termination is also not reported. The listed secondary outcomes do not have posted efficacy results. These limitations leave the intended design identifiable but prevent a statistical assessment of treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate Vadadustat for Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) Who Are Hyporesponsive to Erythropoiesis Stimulating Agents — NCT03140722.
- Registry record last updated 2021-02-21; status last verified 2021-02.
- Results first posted 2021-02-21.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a randomized, open-label, parallel-group Phase 2 study of vadadustat versus epoetin alfa for anemia in people with dialysis-dependent chronic kidney disease who were hyporesponsive to erythropoiesis stimulating agents. Vadadustat was described as a daily oral dose adjustable based on hemoglobin; epoetin alfa was dose-adjustable based on hemoglobin and clinical indication.
The primary endpoint was change from baseline in hemoglobin over time, from baseline through up to 20 weeks. Secondary outcomes included hemoglobin patterns and target-range values, rescue treatment, transfusion, biomarkers, iron use and sufficiency, and resource use. The study is listed as terminated, with enrollment of N=2. The registry states that no efficacy analyses were conducted and that participant results cannot be reported to protect privacy. The available record therefore does not provide a comparative efficacy result.