A 4-Week Dose-Ranging and Efficacy Trial of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A 4-Week Dose-Ranging and Efficacy Trial of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease (NCT01074125), a randomized phase 3 study. The primary outcome is Change in Serum Phosphorus From Baseline to End of Treatment.

2. Clinical Question

The study description places the question in the context of high blood phosphorus in people with kidney failure receiving dialysis. The registry describes the trial as a dose-ranging and efficacy study of ferric citrate and gives a four-week treatment period following a two-week washout period in its official title. The key statistical contrast is not between ferric citrate and usual care or another binder: all three posted arms received ferric citrate at different doses. Consequently, the comparisons describe differences among the tested dose groups over the short treatment period, rather than a comparison with no ferric citrate.

3. Trial Design

The registry describes a phase 3, randomized, parallel-group trial sponsored by Keryx Biopharmaceuticals. It is marked completed. Enrollment is listed as 154. The trial began in 2010-05, and primary completion is listed as 2010-11. Those record dates describe the trial timeline; they do not by themselves establish how long individual participants were followed beyond the stated endpoint timeframe.

The three arm descriptions are 1 g/day, 6 g/day, and 8 g/day of KRX-0502 (ferric citrate). The record says masking was none, so the trial was unmasked. Allocation is recorded as randomized, but the randomization method, sequence generation, concealment procedures, and any stratification factors are not reported in the registry record. The reason for choosing these exact dose levels is not reported in the registry record.

The primary outcome is change in serum phosphorus from baseline to end of treatment, with the timeframe given as baseline and day 28. The outcome description says the mean change was calculated separately for each treatment arm using LOCF, and identifies the ITT Population. The record also includes two secondary outcome measures. Their existence does not establish that they were prespecified in a particular hierarchy or how they were used in decision-making; that information is not reported in the registry record.

Although the study title identifies a two-week washout period before the four-week trial period, details of the washout procedures and their implementation are not reported in the registry record. The original sample-size justification, planned statistical model, target power, planned multiplicity approach, and any interim analyses are not reported in the registry record. The posted values therefore support a description of the recorded design and results, but not a reconstruction of unreported protocol decisions.

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: 3 patients were randomized, but withdrew before initiating study treatment

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT) Population

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: Intent-to-treat

6. Primary Endpoint

The registry lists the primary outcome as Change in Serum Phosphorus From Baseline to End of Treatment, measured over Baseline and day 28.

The primary endpoint is mean change in serum phosphorus from baseline to day 28, measured in mg/dL. It is a continuous outcome: each participant's end-of-treatment measurement is considered in relation to that participant's baseline measurement, and the registry reports the mean change separately for each treatment arm. The outcome description specifies LOCF and the ITT Population.

Serum phosphorus is the laboratory measure at the center of this trial's stated research question. A change endpoint conveys the direction and average size of change over the specified treatment period, while retaining more information about measured values than a simple classification into categories. Comparing the mean changes between dose arms asks whether the average observed change differed between the groups, rather than only whether participants crossed a selected threshold.

The primary endpoint does not by itself describe every participant's response or the distribution of individual changes. The arm-level standard deviations provide information about variability around the means. The registry's outcome description names the analysis population and LOCF handling, but further details about the timing and availability of individual measurements, the exact imputation procedure, and sensitivity analyses are not reported in the registry record. Interpretation should therefore stay tied to the recorded mean changes and their uncertainty, rather than assume additional details about participant-level data or the missing-data process.

7. Results Posted in the Registry

• 6 g/Day: mean -1.86 versus -0.10 on control; difference -1.76 (95% CI -2.35 to -1.17), standardized effect d = -1.17; z-test p = <0.001.
• 8 g/Day: mean -2.13 versus -0.10 on control; difference -2.03 (95% CI -2.71 to -1.35), standardized effect d = -1.22; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Pairwise Comparison of the Mean Change in Serum Phosphorus From Baseline to the End of Treatment

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • 6 g/Day: mean -1.94 versus 0.04 on control; difference -1.98 (95% CI -2.66 to -1.30), standardized effect d = -1.23; z-test p = <0.001.
  • 8 g/Day: mean -2.21 versus 0.04 on control; difference -2.25 (95% CI -3.07 to -1.43), standardized effect d = -1.30; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for 6 g/Day than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for 8 g/Day than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Proportion of Patient With a Serum Phosphorus ≤5.5 mg/dL at the End of Treatment

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • 6 g/Day: 51.0% (26/51) versus 12.0% (6/50) on control; risk difference 39.0 percentage points (95% CI 22.6 to 55.4), risk ratio 4.25 (1.91–9.43); unadjusted two-proportion z-test p = <0.001.
  • 8 g/Day: 57.8% (26/45) versus 12.0% (6/50) on control; risk difference 45.8 percentage points (95% CI 28.8 to 62.8), risk ratio 4.81 (2.18–10.62); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for 6 g/Day than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for 8 g/Day than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes extend the primary laboratory question in two ways: one records pairwise mean changes, and another classifies participants according to whether serum phosphorus was at or below the stated threshold at the end of treatment. In broad terms, both secondary measures point in the same direction as the primary pattern: the higher-dose groups have more favorable measured serum phosphorus results than the 1 g/Day comparator in the posted data. They add a view of the outcome beyond the primary continuous mean, but they do not answer a wholly separate question about long-term or broader clinical outcomes.

The mean-change secondary outcome is closely related to the primary measure, while the threshold outcome converts a continuous laboratory value into a binary classification. That conversion can aid interpretation of the fraction meeting a specified threshold, but it also discards information about how far individual measurements lie from that threshold. The secondary results should therefore be understood as complementary summaries, not independent confirmation of every implication of the primary result.

The posted pairwise secondary calculations are unadjusted. When multiple outcomes and comparisons are considered, the chance of at least one small p-value can increase if no multiplicity plan is used. The registry record does not report the prespecified testing hierarchy or adjustment method, so the secondary p-values should be treated as exploratory or supportive rather than as conclusive stand-alone evidence. Their alignment with the primary outcome is informative, but does not remove uncertainty about multiplicity, missing data, or the analysis choices that are not documented in the record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Pairwise Comparison of the Mean Change in Serum Phosphorus From Baseline to the End of Treatment
• Proportion of Patient With a Serum Phosphorus ≤5.5 mg/dL at the End of Treatment

9. Statistical Interpretation

10. Statistical Methods Explained

Serum phosphorus change is treated as a continuous measure. For each arm, the registry reports a mean change and a standard deviation. The mean describes the average change in that group; the standard deviation describes how spread out participant changes are around the group mean. These quantities answer different questions: a mean estimates the group's average, while a standard deviation indicates how much individual observations vary.

What does a mean difference represent?

The pairwise recalculations compare the mean change in a higher-dose arm with the mean change in the 1 g/Day arm. The estimate is expressed in mg/dL and retains the direction of subtraction used in the calculation. A negative estimate means the mean change in the higher-dose arm is lower, or more negative, than the mean change in the comparator arm. The estimate is an average contrast between groups, not a description of every participant's outcome and not a within-person treatment effect for any particular participant.

The recalculated estimates use the posted arm-level means, standard deviations, and participant counts. The standard deviations are not approximate in these calculations. The confidence intervals reflect uncertainty in the estimated mean differences, given the data and the calculation assumptions. They do not account for design features or adjustments that are not included in an unadjusted calculation, and they should not be mistaken for intervals from the registry's regression analysis.

How should a confidence interval be read?

A confidence interval presents a range of estimates compatible with the observed data under the statistical method. It conveys both the direction and precision of the estimate. When the interval excludes zero, the data are inconsistent with a zero difference at the corresponding conventional two-sided level under that method. That statement is about statistical compatibility, not proof that the true difference has a particular value, nor does it establish clinical importance. The interval's width depends on the variability and amount of information in the groups as well as the method used.

What does the p-value add?

The unadjusted p-value describes how unusual data at least as incompatible with a zero difference would be under a null model of no difference, assuming the calculation's model and conditions hold. The reported values are <0.001 for both primary pairwise comparisons. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of a difference. Because the values are unadjusted, they do not incorporate a correction for multiple testing.

Why does variability matter?

Participants in the same arm do not necessarily have the same change. Standard deviations summarize this between-participant variation. More variability generally makes a group mean less precisely estimated for a fixed amount of data, while more participants generally provide more information about the mean. The recalculated contrasts use pooled standard deviations of 1.504 mg/dL for 6 g/Day versus 1 g/Day and 1.661 mg/dL for 8 g/Day versus 1 g/Day. A pooled standard deviation combines information about spread across the two groups for the standardized effect description; it does not mean the two groups have identical participant-level distributions.

A standardized effect can express a mean contrast relative to pooled variability, which can aid comparison across measures with different units. Such a standardized quantity is not itself a change in mg/dL and does not replace the original-unit estimate. The calculated standardized effects are -1.17 for the 6 g/Day comparison and -1.222 for the 8 g/Day comparison. These are recalculations from posted summary statistics, not additional trial outcomes.

What does the registry's regression result describe?

The registry reports a linear regression analysis involving all three groups and labels its parameter “Mean Difference (Final Values).” It reports -0.338 and p < 0.001, without a confidence interval or further model details in the record. This result is not the same estimand as the pairwise recalculation of change from baseline. The registry record does not report enough model specification to explain the coding, covariate adjustments, or exact contrast represented by that regression value. It is therefore appropriate to report it as the registry's analysis, while keeping it distinct from the pairwise change estimates.

Why can over-dispersion matter in other outcome types?

Over-dispersion is a general statistical issue that arises when count or binary-outcome variability exceeds what a model assumes. If present and ignored, standard errors can be too small and confidence intervals too narrow. The primary outcome is a continuous measure summarized with means and standard deviations, so that particular count-model issue is not the central method described for the primary endpoint. It is still important to match a statistical model to the type and distribution of an outcome rather than assume that one analysis method applies to every endpoint.

The secondary threshold outcome is binary at the participant level, and its registry results are reported as proportions. Its pairwise risk-difference calculations are likewise separate from the continuous-outcome calculations. Different outcome types have different assumptions and uncertainty calculations; a result for one endpoint should not be treated as if it were generated by the method for another.

11. Confidence Intervals and Precision

The primary recalculated confidence intervals are -2.345 to -1.175 mg/dL for 6 g/Day versus 1 g/Day, and -2.714 to -1.346 mg/dL for 8 g/Day versus 1 g/Day. Both intervals are entirely below zero. In the context of the defined contrast, this indicates that the data are compatible with a more negative mean change in each higher-dose arm than in the 1 g/Day arm, under the unadjusted calculation.

Precision is not the same as the size of an estimate. The interval communicates uncertainty around the estimated mean difference; it does not state that the true value is equally likely to be anywhere within its limits, nor does it capture every source of uncertainty in the study. In particular, these recalculated intervals do not reflect an unreported multiplicity adjustment or account for unknown choices in the original analysis plan.

The arm-level standard deviations—1.285, 1.692, and 1.998 mg/dL—show substantial variation in participant-level changes relative to the group averages. Thus, a clearly separated average contrast does not imply uniform individual responses. The number of participants contributing to the primary outcome summaries was 50 in the 1 g/Day arm, 51 in the 6 g/Day arm, and 45 in the 8 g/Day arm.

The registry's regression result has no confidence interval reported. Its p-value alone therefore does not provide a range for that regression estimate's magnitude. The pairwise confidence intervals should not be attached to that separate analysis. More generally, precision statements are specific to the estimand and method that produced them.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures describe illustrative participants per arm for a hypothetical two-arm comparison. They are not the observed enrollment or the original trial's documented design target. The assumptions listed for this illustration are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original trial's own sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a design that would have an 80% chance of detecting the specified effect under the listed assumptions, if that effect and the other assumptions were true. The 90% power column gives the corresponding participants per arm for a higher chance of detecting that same specified effect. These are design-planning concepts, not guarantees about the outcome of a future study.

Rows describing 100%, 75%, or 50% of the observed effect use progressively smaller effects as planning targets. Smaller effects are harder to distinguish from random variation and therefore require more participants per arm under otherwise identical assumptions. The figures are based on observed estimates, which may not equal the effect that would be seen in a new study. They should be read as illustrations for planning rather than as evidence about whether this completed trial had adequate power.

All the listed planning figures for these continuous and binary outcomes are participants per arm, not total event counts. The sample-size assumptions distinguish event-count output for time-to-event outcomes from participant counts for other outcome types; no time-to-event outcome is among the posted measures. These planning values are not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.760; pooled standard deviation σ = 1.504.
2. n = 2 × (1.96 + 0.842)² × 1.504² / -1.760² = 11.5, rounded up to 12 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.76                      # observed difference in means
sigma <- 1.50438156359645                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1074125)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 12 (80% power), 16 (90% power)
 75% of observed effect: n per arm = 21 (80% power), 28 (90% power)
 50% of observed effect: n per arm = 46 (80% power), 62 (90% power)
power.t.test: 12.5 
Simulated power at n = 12 per arm: 0.780 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry's reported analysis is a linear regression across the three groups. Its parameter is labeled “Mean Difference (Final Values),” and the record reports an estimate of -0.338 with p < 0.001. A confidence interval is not reported for this analysis. The result is not presented as either of the pairwise mean-change contrasts calculated from the arm-level summaries.

The recalculated contrasts compare change from baseline in each higher-dose arm with change in the 1 g/Day arm. They use the posted means, standard deviations, and sample sizes and produce unadjusted confidence intervals and p-values. The registry's regression analysis has a different stated parameter and includes all three groups, so the numeric estimates should not be compared as if they were estimates of the same quantity.

The record does not provide enough detail about the regression model to establish its covariates, contrast coding, or relationship to any prespecified analysis plan. No discrepancy is identified between the registry's reported analysis and the posted results, but the different estimands still need to be kept separate. The sponsor analysis is the analysis reported in the registry; the pairwise calculations are useful as transparent, unadjusted comparisons from summary statistics, not as a replacement for the regression analysis.

15. Multiplicity, Missing Data and Analysis Populations

The record lists a primary outcome and two secondary outcome measures, and the posted calculations include more than one pairwise comparison. The pairwise recalculated p-values are explicitly unadjusted. No multiplicity-control procedure, hierarchy among secondary outcomes, or family of hypotheses is reported in the registry record. Without that information, the nominal p-values should not be interpreted as if they necessarily preserve a study-wide error rate across every outcome and comparison.

Multiplicity matters because repeated testing creates more opportunities to observe results that appear statistically notable by chance, even when the individual tests use conventional thresholds. The issue does not change the observed arm means or the calculated contrasts; it changes how confidently a collection of tests can be interpreted as confirmatory. It is therefore appropriate to distinguish the primary endpoint from secondary findings and to avoid treating each unadjusted result as an independent confirmation.

The primary endpoint description specifies the ITT Population and LOCF. The record does not explain the detailed missing-data patterns, the number of participants with unavailable measurements, the exact implementation of LOCF, or whether sensitivity analyses using other missing-data methods were conducted. Carrying a last observed value forward is an imputation approach; its implications depend on why data are missing and whether the carried-forward value remains a reasonable representation of the participant's later measurement. Those conditions are not documented in the registry record.

Participant counts differ across posted outcome summaries, but reasons for the differences and the handling of missing outcome values beyond the stated LOCF description are not reported in the registry record. The record also does not specify the full analysis populations for each secondary measure. It is not possible to infer from these summaries whether missingness was balanced across arms or whether it was related to outcome values.

The original sample-size justification, planned primary model details, interim analyses, and prespecified multiplicity approach are not reported in the registry record. These omissions limit reconstruction of the intended statistical plan. They do not erase the posted numerical findings, but they constrain how fully the findings can be assessed as confirmatory evidence under the original protocol.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure congestive (3.9%), renal transplant (3.9%), hypertensive crisis (2.1%), hypertension (2.1%), cellulitis (2.1%).

The registry reports serious adverse events in all three dose groups. The at-risk counts are 51 for 1g/Day, 52 for 6g/Day, and 48 for 8g/Day; the corresponding counts with serious adverse events are 6, 7, and 9. These are counts, not rates adjusted for exposure time. The record does not give the duration of safety observation by participant or enough detail to compare event timing.

The registry also reports other adverse events: 34 participants in the 1g/Day group, 43 in the 6g/Day group, and 41 in the 8g/Day group, with at-risk counts of 51, 52, and 48, respectively. The registry lists serious-event terms including cardiac failure congestive and renal transplant at 3.9% each, and hypertensive crisis, hypertension, cellulitis, and acute myocardial infarction at 2.1% each. Arm-specific attribution for these listed terms is not reported in the registry record.

Deaths are not reported in the registry record. These summaries do not establish that an event was caused by study treatment, and the counts alone do not provide a complete comparative safety assessment. The study's short stated treatment period and the available event summaries also do not answer questions about safety beyond the recorded observation.

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

The posted primary results show that mean serum phosphorus change over the stated treatment period was more negative in the 6 g/Day and 8 g/Day arms than in the 1 g/Day arm. The unadjusted pairwise recalculations have confidence intervals entirely below zero and p-values of <0.001. This is a description of the registry's recorded laboratory outcome and its statistical uncertainty under the recalculation method.

The findings do not show how ferric citrate compares with placebo, no treatment, or another phosphate binder, because all three arms received ferric citrate at different doses. They do not establish that one dose is best, or that a measured laboratory change translates into a particular health outcome. The registry record reports serum phosphorus endpoints, not a complete evaluation of clinical outcomes. No inference about long-term persistence can be drawn from the stated day 28 endpoint alone.

The arm means describe averages, and individual changes varied. A group-level difference does not mean every participant in a higher-dose arm had a larger decrease than every participant in the 1 g/Day arm. Nor does statistical significance by itself establish whether the size of a difference is important to patients or clinicians; no threshold for clinical importance is reported in the registry record.

The analysis is also bounded by documentation. The registry identifies an ITT Population and LOCF for the primary outcome, but details of missing data and sensitivity analyses are not reported. The original analysis plan, multiplicity procedures, and regression-model specifications are not reported in the registry record. These limitations make it important to separate the observed statistical pattern from stronger conclusions about treatment effects, safety, or clinical value.

Overall, the data support a difference in the short-term mean serum phosphorus changes between the higher-dose arms and the low-dose active comparator as analyzed in the posted calculations. They do not independently establish what those differences mean beyond this outcome, period, and trial population.

18. Why This Trial Matters Statistically

This trial illustrates why the choice of comparator is central to interpreting a dose-ranging study. The 1 g/Day arm is an active ferric citrate dose, so the pairwise results address differences among doses rather than the effect of using ferric citrate compared with not using it. That distinction defines the question the estimates can answer.

It also shows why estimates should be read together with uncertainty and outcome variability. The mean contrasts and their confidence intervals describe average differences, while the arm standard deviations show that participant-level changes were dispersed. Reporting only p-values would omit both the magnitude in mg/dL and the precision of the estimates.

The registry provides a reported regression result alongside outcome summaries from which pairwise calculations can be made. The stated parameter for the regression analysis differs from the pairwise change estimand. Keeping those analyses distinct is a practical lesson in estimand clarity: two numbers from the same study need not answer the same question merely because both concern serum phosphorus.

Finally, the trial has multiple reported endpoints and comparisons, while the registry record does not report a multiplicity strategy or the full original analysis plan. Statistical interpretation requires attention not only to the pattern of results, but also to which question was primary, how missing observations were handled, and whether multiple tests were accounted for. A transparent distinction between documented results and unreported methods is essential to a careful reading.

19. 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 registry record does not report the randomization sequence method, allocation concealment, stratification, or detailed implementation of the unmasked design. These omissions limit assessment of how well the assigned groups may have been protected from selection or measurement biases. The record identifies the trial as randomized and unmasked, but those labels alone do not provide all design details.

The primary results use the ITT Population and LOCF, but the record does not report the amount or pattern of missingness, the exact imputation procedures, or sensitivity analyses. It is therefore difficult to assess how dependent the mean changes are on the approach to missing observations. Participant counts also differ across outcome summaries, and reasons are not reported.

The pairwise results are recalculated without adjustment for multiple comparisons. The registry does not report a prespecified multiplicity plan, the original sample-size justification, or enough detail to reconstruct the regression analysis. The reported regression estimate lacks a confidence interval and has a different stated parameter from the recalculated change contrasts. This limits direct comparison between analyses.

All arms received ferric citrate, so the trial record as described does not support a comparison with placebo or another treatment. The primary outcome timeframe is baseline and day 28, and longer-term results are not reported in the registry record. The posted safety summaries give event counts but do not provide detailed timing, exposure-adjusted rates, or arm-specific allocation for the listed serious-event terms. These are limitations in what the record documents; they should not be filled in by assuming unreported protocol or analysis details.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A 4-Week Dose-Ranging and Efficacy Trial of KRX-0502 (Ferric Citrate) in Patients With End-Stage Renal Disease — NCT01074125.
• Registry record last updated 2014-12-04; status last verified 2014-12.
• Results first posted 2014-12-04.
• 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.

23. Record Summary

NCT01074125 is a completed, randomized, unmasked, parallel-group phase 3 trial of KRX-0502 (ferric citrate) in people with end-stage renal disease and hyperphosphatemia. The three arms received 1 g/day, 6 g/day, or 8 g/day, and enrollment was 154. The primary endpoint was mean change in serum phosphorus from baseline to day 28 in the ITT Population, with LOCF specified.

The posted primary summaries and pairwise recalculations show more negative mean changes in the 6 g/Day and 8 g/Day arms than in the 1 g/Day arm. The recalculated contrasts have unadjusted p-values of <0.001, with confidence intervals below zero. The registry also reports a three-group linear regression analysis of final values. Two secondary outcomes and adverse-event summaries are posted.

The registry record does not report the original sample-size justification, multiplicity strategy, detailed missing-data analyses, or full regression-model specification. Interpretation is consequently limited to the recorded outcomes, comparisons, and documented methods.