Incidence of Hypophosphatemia After Treatment With Iron Isomaltoside/Ferric Derisomaltose vs Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Incidence of Hypophosphatemia After Treatment With Iron Isomaltoside/Ferric Derisomaltose vs Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia (NCT03238911), a randomized phase 3 study. The primary outcome is Incidence of Hypophosphatemia (S-phosphate Level <2 mg/dL).

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, open-label, parallel-group trial sponsored by Pharmacosmos A/S. It compared intravenous iron isomaltoside/ferric derisomaltose with intravenous ferric carboxymaltose in participants with iron deficiency anaemia. The registry record reports an enrollment of 123 and a completed trial. The recorded start date was 2017-10-24, and the primary completion date was 2018-06-19.

The primary outcome was assessed in a safety analysis set, defined in the record as participants who received at least one dose of the investigational product. The outcome window ran from baseline to day 35. The record reports 63 participants in the iron isomaltoside/ferric derisomaltose primary outcome group and 60 in the ferric carboxymaltose group. The outcome is a count of participants meeting the event definition, not a continuous measurement of phosphate concentration.

Randomization supports a comparison between assigned treatment groups, while the parallel design means participants were assigned to a treatment arm rather than crossing between treatments. Open-label status means treatment assignment was not masked. The registry record does not report details of sequence generation, allocation concealment, or procedures used to reduce the possible effects of knowing treatment assignment.

The trial also recorded secondary outcomes concerning hypophosphatemia at day 35, time with hypophosphatemia, phosphate changes, urinary phosphate excretion, and measures related to fibroblast growth factor 23 and vitamin D. The record lists 18 outcome measures and 76 analyses. It does not report the trial’s original sample-size justification or the full statistical plan in the information summarized for these results.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set: included all subjects who received at least one dose of the investigational product.

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 Incidence of Hypophosphatemia (S-phosphate Level <2 mg/dL), measured over Baseline to day 35.

The primary endpoint counted participants with hypophosphatemia at any time from baseline through day 35. Hypophosphatemia was defined as a serum phosphate level below 2 mg/dL. The endpoint therefore captures whether a participant crossed the stated threshold during the follow-up window; it does not describe the magnitude or duration of every phosphate change.

A binary endpoint such as this is useful for comparing the frequency of a prespecified event between treatment groups. It translates repeated observations over a follow-up period into a participant-level event count. That makes the group comparison straightforward to describe, but it also means the count does not convey when the event occurred, how many measurements were below the threshold for a given participant, or how low the phosphate level became.

The record lists related secondary measures, including time with hypophosphatemia and phosphate levels at selected follow-up times. Those measures address aspects of timing and measurement that the primary incidence endpoint does not capture. The primary endpoint’s stated population was the safety analysis set, so the reported counts concern participants who received at least one dose, rather than an explicitly described intention-to-treat population.

The threshold and assessment window define what the endpoint can answer. The result concerns recorded hypophosphatemia below the specified serum phosphate level from baseline to day 35; it does not, on its own, establish the clinical consequences of an event or its course after that window.

7. Results Posted in the Registry

• Ferric Carboxymaltose: 75.0% (45/60) versus 7.9% (5/63) on control; risk difference 67.1 percentage points (95% CI 54.2 to 79.9), risk ratio 9.45 (4.02–22.19); unadjusted two-proportion 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.

Proportion of Subjects With Hypophosphatemia on Day 35 ( S-phosphate Level <2.0 mg/dL)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ferric Carboxymaltose: 41.4% (24/58) versus 1.7% (1/59) on control; risk difference 39.7 percentage points (95% CI 26.6 to 52.8), risk ratio 24.41 (3.41–174.59); 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 Ferric Carboxymaltose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Incidence of Protocol-defined Serious or Severe Hypersensitivity Reactions

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ferric Carboxymaltose: 0.0% (0/60) versus 1.6% (1/63) on control; risk difference -1.6 percentage points (95% CI -4.7 to 1.5); unadjusted two-proportion z-test p = 0.327.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ferric Carboxymaltose and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes addressing hypophosphatemia at day 35, time with hypophosphatemia, changes in serum phosphate, urinary phosphate excretion, fibroblast growth factor 23, and vitamin D. Taken together, these outcomes were intended to describe related features of the phosphate response, including timing and laboratory changes, rather than only whether the primary threshold was crossed at any point during follow-up.

The detailed secondary results in the registry record include a day-35 hypophosphatemia comparison and a comparison of protocol-defined serious or severe hypersensitivity reactions. For the other listed secondary outcomes, results are not reported in the registry record. The secondary information therefore does not support a complete account of the time course or all related laboratory measures. The day-35 outcome is related to the primary result but uses a specific assessment time rather than the primary endpoint’s any-time window.

Secondary analyses can help contextualize a primary finding, but they generally carry less weight when many outcomes or tests are examined and no multiplicity strategy is reported. Without a stated hierarchy or adjustment, a notable secondary result may reflect chance as well as a real pattern. The registry record does not report a multiplicity adjustment for these analyses. The primary result should therefore remain distinct from exploratory or supportive findings, and the secondary outcomes should not be treated as independent confirmation of the primary comparison.

Differences in outcome definitions and analysis populations also matter. A result at day 35 does not answer exactly the same question as an event occurring at any point through day 35, and a safety event comparison is not a measure of phosphate response. The secondary findings add context but do not replace the primary endpoint’s stated definition and analysis.

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

• Time With Hypophosphatemia ( S-phosphate Level <2.0 mg/dL)
• Proportion of Subjects With Hypophosphatemia on Day 35 ( S-phosphate Level <2.0 mg/dL)
• Absolute [∆] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35
• Relative [%] Changes in S-phosphate From Baseline to Day 1, 7, 8, 14, 21, and 35
• Change From Baseline in Fractional Phosphate Urinary Excretion
• Change in Concentration of (Intact) Fibroblast Growth Factor 23 (iFGF23) From Baseline to Day 1, 7, 8, 14, 21, and 35
• Change in C-terminal Fibroblast Growth Factor 23 (cFGF23) From Baseline to Days 1, 7, 8, 14, 21, and 35
• Change in Vitamin 25-Hydroxyvitamin D (Vitamin D 25) From Baseline to Days 1, 7, 8, 14, 21, and 35

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary: each participant either met the hypophosphatemia definition during the stated window or did not. The posted group results are counts of participants with the event, alongside the numbers assessed in each arm. An unadjusted comparison uses these group summaries directly, without adjustment for other variables or stratification factors.

Risk differences and direction

A risk difference compares the event proportions in two groups by subtracting one group’s proportion from the other’s. Its sign depends on the order of subtraction. The recalculated estimate is expressed as ferric carboxymaltose minus iron isomaltoside/ferric derisomaltose, so a positive estimate indicates a higher observed event proportion in the former group. The registry-reported estimate uses the groups in the opposite order and is negative. These different signs do not indicate conflicting results; they reflect the direction in which the contrast is written.

The recalculated risk difference is 0.671, with a 95% confidence interval from 0.542 to 0.799. This is a simple, unadjusted recalculation from the posted counts. It is distinct from the registry’s Cochran-Mantel-Haenszel analysis, which reports a risk difference of -67.0, a 95% confidence interval from -77.4 to -51.5, and p < 0.001. The registry record does not give details of any strata used in that analysis, so the basis for adjustment cannot be described further.

Other measures of association

For the primary outcome, the recalculated risk ratio is 9.45, with a confidence interval from 4.024 to 22.19. The recalculated odds ratio is 34.8, with a confidence interval from 11.77 to 102.9. These measures express the comparison differently from a risk difference: a risk ratio compares event proportions, whereas an odds ratio compares event odds. They are recalculations from the posted summary data, not separate sponsor-reported estimates. When the event is frequent in one group, an odds ratio can appear more extreme than a risk ratio, so the measures should not be treated as interchangeable.

Confidence intervals and tests

A confidence interval describes the range of effect estimates compatible with the data under the method used, at the stated confidence level. It conveys precision as well as direction. A narrower interval indicates greater precision than a wider interval, while an interval that includes no difference leaves a range of values compatible with no group difference under that method. A p-value summarizes evidence against a specified null hypothesis under the test assumptions; it does not measure the probability that the treatment difference is real.

The primary outcome’s recalculated interval is wholly on the positive side for the stated contrast. The registry-reported interval is wholly on the negative side because its group order is reversed. The registry analysis reports p < 0.001. The recalculated unadjusted comparison reports p < 0.001. These p-values arise from analyses that are not identical, so the reported value should not be substituted for the sponsor’s analysis.

What the counts cannot show

Participant counts do not retain all information from repeated phosphate measurements. They indicate whether the threshold was crossed during follow-up, but not the number of low readings per participant, the duration of low values, or the degree below the threshold. The registry lists secondary outcomes that address timing and laboratory changes, but results for outcomes not detailed in the posted analysis are not reported in the registry record.

The primary population is the safety analysis set, defined by receipt of at least one dose. That definition is not the same as an explicitly stated intention-to-treat population. The record does not describe the number of participants with missing endpoint measurements, imputation procedures, or sensitivity analyses for missing data. These omissions limit assessment of how incomplete observations, if any, might have affected the comparison.

Because treatment assignment was open-label, knowledge of assignment could potentially affect aspects of participant behavior, clinical management, or outcome assessment. The endpoint is based on a laboratory threshold, but the record does not describe whether laboratory assessment or event classification was blinded. This does not establish that bias occurred; it identifies a design feature relevant to evaluating the result.

Secondary analyses and multiplicity

The record lists multiple secondary outcomes and analyses. When many hypotheses are examined, the chance of at least one apparently notable result can increase if each is interpreted without accounting for multiplicity. The registry information summarized for these results does not report a multiplicity adjustment or a hierarchy that would establish which secondary tests were confirmatory. Secondary findings therefore warrant more cautious interpretation than the prespecified primary comparison, particularly when they are not supported by a clearly reported multiplicity plan.

The sample-size illustrations use the observed effect as a planning reference and assume a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are hypothetical planning calculations, not evidence that the study was originally designed with those assumptions. The trial’s original sample-size justification is not reported in the registry record.

11. Confidence Intervals and Precision

The primary unadjusted risk-difference estimate is 0.671, with a 95% confidence interval from 0.542 to 0.799, for ferric carboxymaltose minus iron isomaltoside/ferric derisomaltose. This interval is entirely above zero, indicating that the compatible estimates under this calculation favor a higher observed event proportion in the ferric carboxymaltose group. The interval is bounded, but its width also shows that the exact magnitude is not known without uncertainty.

The registry-reported Cochran-Mantel-Haenszel estimate is -67.0, with a 95% confidence interval from -77.4 to -51.5. The direction is reversed because the contrast is expressed in the opposite group order. The interval also remains on one side of zero. The registry estimate and the simple recalculation use different methods and presentation scales; the registry’s own analysis is the principal reported analysis.

A confidence interval is not a range that contains the true effect with certainty, nor does it describe the spread of individual participant outcomes. It reflects sampling uncertainty under the analysis method and its assumptions. Wider intervals generally leave greater uncertainty about the size of an effect; narrower intervals indicate greater precision. Precision should be considered alongside the estimate’s direction, the endpoint definition, and the design.

The primary groups include 63 and 60 participants. Those group sizes and the event counts are important context for the interval. The record does not report a confidence interval for each group’s event proportion in the primary results, so no such interval should be inferred. The secondary day-35 result has its own interval and differs from the primary outcome because it concerns a specific time point rather than any time through day 35.

Statistical precision does not resolve the limits of follow-up, missing-data reporting, or generalizability. The interval pertains to the stated comparison and analysis, not to every possible population or treatment context.

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 sample-size illustrations are planning calculations based on the observed effect, not the trial’s original design assumptions. For these binary participant outcomes, the figures are participants per arm. They are not total event counts. The calculation assumptions listed in the registry-derived information are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row uses a stated fraction of the observed effect as the effect to detect.

The 80% power column describes the number of participants per arm estimated to give an 80% chance of detecting the assumed difference if that difference is real and the calculation assumptions hold. The 90% power column applies the same idea with a higher probability of detection, which generally requires more participants. For the primary outcome, the illustration based on 100% of the observed effect gives 8 participants per arm for 80% power and 10 for 90% power. The corresponding figures for 75% of the observed effect are 13 and 17; for 50% of the observed effect, they are 25 and 33.

These illustrations use an unusually large observed contrast as their reference. Planning for a smaller effect requires more participants: the listed figures increase as the assumed effect decreases. This pattern is a general feature of power calculations, not a claim about what effect a future study will observe. The original sample-size justification and assumptions used to plan the completed trial are not reported in the registry record.

This is not observed power. It is a forward-looking planning illustration that applies stated assumptions to an effect estimated from the trial data. It should not be used to judge whether the completed trial was adequately powered according to its original protocol.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.079; treatment proportion p₁ = 0.750; average p̄ = 0.415.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6967 = 1.3656.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5105 = 0.4296.
4. n = (1.3656 + 0.4296)² / (0.6706)² = 7.2, rounded up to 8 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
p0 <- 0.0793650793650794                          # control proportion
p1 <- 0.75                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(3238911)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 8 (80% power), 10 (90% power)
 75% of observed effect: n per arm = 13 (80% power), 17 (90% power)
 50% of observed effect: n per arm = 25 (80% power), 33 (90% power)
power.prop.test: 7.2 
Simulated power at n = 8 per arm: 0.899 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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-reported primary analysis uses the Cochran-Mantel-Haenszel method and reports a risk difference of -67.0, with a 95% confidence interval from -77.4 to -51.5 and p < 0.001. The group order in that result is iron isomaltoside/ferric derisomaltose followed by ferric carboxymaltose. The negative sign therefore corresponds to a lower event proportion in the first-listed group.

The simple recalculation uses the posted event counts and expresses the contrast in the reverse direction, ferric carboxymaltose minus iron isomaltoside/ferric derisomaltose. It gives a risk difference of 0.671, with a 95% confidence interval from 0.542 to 0.799 and p < 0.001. The direction agrees after accounting for group order. The values should not be treated as identical estimates: one is the registry-reported Cochran-Mantel-Haenszel analysis, and the other is an unadjusted recalculation from summary counts.

The registry record does not flag a discrepancy between the posted result and the recalculation. The sponsor’s own analysis remains the primary reported analysis; the recalculation serves as a transparent, unadjusted comparison rather than a replacement for it. The record does not provide additional detail about the strata or other implementation choices behind the Cochran-Mantel-Haenszel result.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 18 outcome measures, 16 posted secondary outcomes, and 76 analyses. This is a substantial set of opportunities to examine different endpoints, time points, and comparisons. When multiple hypotheses are tested, the probability of observing at least one small p-value by chance can rise if each result is judged in isolation. Multiplicity methods can address this issue, but their use depends on the planned testing strategy and the role assigned to each outcome.

A multiplicity plan may specify a hierarchy of outcomes, control an overall error rate, or identify analyses as exploratory. The registry record does not report whether any adjustment was used, how testing was ordered, or which secondary analyses were intended to be confirmatory. Without those details, individual secondary p-values should be interpreted cautiously. The primary result is the clearest basis for the main comparison because it is identified as the primary outcome, but the record does not provide the full protocol-level testing plan.

The primary analysis population is described as the safety analysis set, including participants who received at least one dose. The record does not report an intention-to-treat analysis population for this endpoint. It also does not describe the amount or pattern of missing outcome data, how missing measurements were handled, or whether sensitivity analyses assessed different assumptions about missingness. Consequently, the effect of missing observations on the estimates cannot be evaluated from the registry information summarized for these results.

The endpoint relies on assessment of serum phosphate over a follow-up window. The record states the threshold and window, but does not explain how measurements that were unavailable at particular times were treated when determining whether an event occurred. Nor does it describe whether outcome assessment was blinded. These omissions do not demonstrate that the analysis was biased or that data were missing; they limit what can be concluded about those possibilities.

Details of randomization implementation, allocation concealment, and the full statistical analysis plan are not reported in the registry record. Their absence from the available record restricts assessment of prespecification and analysis choices. Conclusions should therefore focus on the reported comparison and avoid assuming unreported methods.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypersensitivity (1.6%).

For serious adverse events, the registry reports 1 affected participant among 63 in the iron isomaltoside/ferric derisomaltose group and 0 among 60 in the ferric carboxymaltose group. The listed serious adverse event term is hypersensitivity, reported as 1.6% for the former group. Deaths were 0 in both groups. These are counts within the trial, not estimates of how often such events would occur in other populations.

The record separately reports other adverse events in 0 of 63 participants in the iron isomaltoside/ferric derisomaltose group and 25 of 60 in the ferric carboxymaltose group. These figures are distinct from the serious adverse event counts and should not be combined with them. The registry also lists a secondary outcome for protocol-defined serious or severe hypersensitivity reactions: 1 participant in the iron isomaltoside/ferric derisomaltose group and 0 in the ferric carboxymaltose group. Its unadjusted risk-difference interval includes zero, and the recalculated p-value is 0.327.

Small event counts provide limited precision for comparing safety outcomes. The record does not supply detailed descriptions of all adverse events, their timing, duration, or relationship to treatment. These figures should be read as the trial’s reported safety observations over the stated period, not as a complete characterization of risk.

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

The primary result describes a difference in recorded hypophosphatemia between the randomized treatment groups during follow-up from baseline to day 35. The event was defined as a serum phosphate level below 2 mg/dL. The posted counts were 5 of 63 participants in the iron isomaltoside/ferric derisomaltose arm and 45 of 60 in the ferric carboxymaltose arm. The registry-reported comparison and the unadjusted recalculation point in the same direction when their group order is taken into account.

This finding is specific to the endpoint, population, treatments, and follow-up described in the record. The primary outcome captures whether the threshold was crossed, not the duration or depth of each low value. It does not establish what happened after day 35, and it does not quantify every aspect of phosphate physiology or related clinical outcomes. Secondary outcomes were intended to examine some related measures, but results for several listed outcomes are not reported in the registry record.

A statistically clear difference does not, by itself, establish the clinical importance of that difference. Clinical importance depends on the consequences of the event and the wider balance of outcomes, and the registry information summarized for this result does not establish those consequences. Nor does a finding in this trial guarantee the same pattern in every setting or population.

The open-label design and the limitations in reporting about missing data, outcome assessment, and the full analysis plan should be considered when interpreting the findings. The randomized design supports a comparative interpretation, but the available registry record does not answer every question about implementation or analysis. The results are evidence about the recorded trial outcomes, not medical advice or a recommendation for an individual treatment decision.

18. Why This Trial Matters Statistically

This trial illustrates how a binary safety endpoint can produce an interpretable group comparison: the outcome is defined by a threshold, and the result is expressed as the number of participants who crossed it during a specified window. The absolute event counts make the observed pattern clear, while risk differences and confidence intervals describe the size and uncertainty of the comparison.

It also shows why contrast direction must be checked before comparing estimates. The registry-reported risk difference and the unadjusted recalculation have opposite signs because the order of the groups is reversed. Once that distinction is made, the analyses point in the same direction, although they remain different methods and should not be conflated.

The record offers a useful distinction between a sponsor-reported analysis and a simple recalculation from group summaries. The recalculation can help readers understand the posted counts, but it does not reproduce every feature of the registry analysis. Giving priority to the sponsor’s reported method while labeling the recalculation accurately avoids treating a straightforward summary comparison as if it were the trial’s full statistical analysis.

Finally, the many listed outcomes underline the importance of prespecified analysis plans, multiplicity control, and complete reporting. Secondary measures can illuminate timing and related physiology, but without their results and a reported testing strategy they cannot be weighed as confidently as the primary comparison. Precision, design, missing-data reporting, and outcome definitions all contribute to a responsible statistical interpretation.

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 primary outcome window ends at day 35, so the record does not establish whether the observed pattern continued, resolved, or changed after that point. The binary endpoint also omits details about event duration, repeated low readings, and the magnitude of phosphate changes. Although related secondary measures are listed, results for several are not reported in the registry record.

The trial was open-label. Treatment assignment was therefore known, and the record does not report whether laboratory assessment or event classification was blinded. Because the endpoint uses a serum phosphate threshold, knowledge of assignment may be less directly relevant to the laboratory value itself than to some subjective outcomes, but the record does not provide enough detail to assess measurement procedures or management decisions.

The primary population is the safety analysis set of participants who received at least one dose. The registry record does not report an intention-to-treat analysis for the primary endpoint, the extent of missing endpoint data, or the methods used to handle missing measurements. It also does not give the original sample-size justification or full analysis plan. These gaps limit assessment of the intended analysis and the effect of any incomplete data.

The record lists many outcomes and analyses but does not report a multiplicity strategy. Secondary results may therefore be more vulnerable to chance findings when interpreted individually. The available information also does not describe the randomization implementation or allocation concealment. These reporting limits do not invalidate the posted estimates, but they restrict a complete appraisal of bias, robustness, and generalizability.

The primary comparison comes from 123 enrolled participants, with 63 and 60 in the reported primary outcome groups. The trial’s results should not be assumed to represent other populations, treatment regimens, or follow-up periods without additional evidence.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Incidence of Hypophosphatemia After Treatment With Iron Isomaltoside/Ferric Derisomaltose vs Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia — NCT03238911.
• Registry record last updated 2020-02-25; status last verified 2020-02.
• Results first posted 2020-02-25.
• 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

The registry record describes a completed, randomized, open-label, parallel-group phase 3 trial sponsored by Pharmacosmos A/S. It compared intravenous iron isomaltoside/ferric derisomaltose with intravenous ferric carboxymaltose in people with iron deficiency anaemia. Enrollment was 123; the recorded start date was 2017-10-24, and primary completion was 2018-06-19.

The primary safety endpoint counted participants with serum phosphate below 2 mg/dL at any time from baseline through day 35. The posted counts were 5 of 63 in the iron isomaltoside/ferric derisomaltose group and 45 of 60 in the ferric carboxymaltose group. The registry-reported Cochran-Mantel-Haenszel risk difference was -67.0, with a 95% confidence interval from -77.4 to -51.5 and p < 0.001; its group order is the reverse of the unadjusted recalculation discussed in the analysis.

The record lists secondary biochemical and safety outcomes, but does not report the original sample-size justification, full statistical plan, multiplicity approach, or details of missing-data handling. These limits should accompany interpretation of the posted results.