Study of Zemplar iv in Patients With End Stage Chronic Kidney Disease, Undergoing Haemodialysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Zemplar iv in Patients With End Stage Chronic Kidney Disease, Undergoing Haemodialysis (NCT01084538), a registered phase not stated study. The primary outcome is Percentage of Subjects Achieving at Least a 40% Reduction of iPTH (Intact Parathyroid Hormone) From Baseline.

2. Clinical Question

The study was intended to gather further information on outcomes with Zemplar injections in routine practice. Its setting was Croatia and Serbia, and the official title describes a one-year, multicountry, multicenter study. The stated clinical context is people on hemodialysis whose condition was not adequately controlled with oral calcitriol or alfacalcidol. The listed arm describes end stage chronic kidney disease with secondary hyperparathyroidism.

This is a question about an observed clinical outcome among people receiving the intervention, not a randomized comparison of treatments. Without a suitable comparison group, the primary outcome can describe how often the threshold was reached in the study population, but cannot by itself establish how outcomes would have differed under another treatment or without treatment. The primary outcome result is not reported in the registry record.

3. Trial Design

This was a post-marketing observational study of intravenous Zemplar (paricalcitol) in routine clinical use. The study description identifies Croatia and Serbia as the participating countries, while the official title describes a one-year, multicountry, multicenter study. The registry lists an enrollment of 181 and an end stage chronic kidney disease arm. Its arm description specifies secondary hyperparathyroidism as iPTH > 300 pg/mL.

The population was described as having end stage chronic kidney disease and undergoing hemodialysis. The official title further characterizes participants as not adequately controlled with oral vitamin D receptor activators, naming calcitriol or alfacalcidol. The listed intervention is Zemplar IV, or paricalcitol IV. The study summary says the aim was to obtain further data on outcomes during routine clinical use.

The record does not describe a randomized allocation, and allocation is not stated. It does not identify a like-for-like control group. Consequently, the design is not a randomized head-to-head trial and does not support interpreting differences between treatment groups as randomized treatment effects. The registry record also does not report the protocol details for treatment decisions, follow-up procedures, or handling of changes in clinical care.

The study status is completed. The recorded start is 2007-09, and primary completion is recorded as 2010-06. The primary outcome timeframe is baseline through 12 months. The primary endpoint is the percentage of participants achieving at least a 40% reduction in iPTH from baseline. Three secondary outcomes are named: achieving iPTH less than or equal to 300 pg/mL, time to that iPTH level, and clinically meaningful hypercalcemia defined as corrected serum calcium > 11.0 mg/dL at two consecutive measurements.

The registry record does not report the primary outcome estimate or the results for these secondary outcomes. It does not report the statistical analysis plan, a sample-size justification, or whether any interim analyses were planned. These absences limit what can be concluded about the study’s analysis and its clinical findings.

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: Safety population consists of 181 participants who received at least one dose of drug. Of those, 175 were included in the full analysis set. Six participants were excluded; five due to initial intact parathyroid hormone values less than 300 picograms per milliliter and one suffered a serious adverse event before the first evaluation (study visit).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of the 175 participants in the full analysis set, one participant was excluded from the analysis due to missing data.

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 Percentage of Subjects Achieving at Least a 40% Reduction of iPTH (Intact Parathyroid Hormone) From Baseline, measured over Baseline through 12 months.

The primary endpoint is the percentage of participants achieving at least a 40% reduction in intact parathyroid hormone (iPTH) from baseline through 12 months. It is a threshold-based outcome: each participant either meets the specified reduction threshold during the defined timeframe or does not. The reported measure would therefore express the share of the analyzed population meeting that criterion.

A threshold can make a clinical outcome easier to interpret than a change in a laboratory value alone, because it describes the proportion reaching a prespecified degree of reduction. It also discards information about the size of changes within each category. Participants who fall just short of the threshold and those with little change are grouped together as not achieving it, while participants who exceed the threshold are grouped together as achieving it. The percentage therefore does not describe the full distribution of individual iPTH changes.

For this outcome to be interpreted, the analyzed population and missing-data handling matter. The record states that the full analysis set included 175 participants and that one participant was excluded from the analysis due to missing data. It does not provide the observed percentage achieving the endpoint, a confidence interval, or further details about the analysis population. The registry record therefore defines what was to be measured but does not report how often the endpoint occurred.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes an observational study, not a randomized comparison. That distinction determines what statistical claims are supportable. In a randomized study, treatment assignment can, under appropriate conditions, make groups comparable with respect to measured and unmeasured factors at the outset. Here, allocation is not stated, and the record does not identify a like-for-like control group. An observed outcome among participants receiving paricalcitol can be described, but it cannot by itself isolate the effect of treatment from other explanations.

What does the primary percentage represent?

The primary outcome is the percentage achieving at least a 40% reduction in iPTH from baseline through 12 months. This is a binary outcome at the participant level: a participant either meets the threshold or does not. The percentage is a summary of the frequency of meeting the criterion in the analysis population. It is not the average reduction in iPTH, and it does not describe how far above or below the threshold individual participants were.

For a percentage to be informative, readers need its numerator, denominator, and an uncertainty measure such as a confidence interval. The numerator would count participants meeting the endpoint, and the denominator would identify the population used in calculating the percentage. The registry record states that the full analysis set comprised 175 participants and that one participant was excluded from the analysis due to missing data, but it does not report the endpoint numerator, percentage, or confidence interval. Thus, the endpoint’s frequency and precision cannot be evaluated from the record.

What does a confidence interval tell a reader?

In general, a confidence interval communicates the statistical uncertainty around an estimated quantity. For a proportion, it indicates a range of values compatible with the observed data under the interval’s assumptions. A narrow interval indicates greater precision than a wide interval. An interval does not correct for bias from selection, confounding, outcome measurement, or missing data, and it does not make an observational comparison causal. No confidence interval for the primary endpoint is reported in the registry record.

Why is there no treatment-effect contrast?

The registry does not identify a control group suitable for a like-for-like comparison. A single-group proportion answers a descriptive question about the participants included in the analysis. It does not supply the counterfactual outcome that those same participants would have experienced under a different treatment. In observational research, treatment choices and participant characteristics may be related; without information and methods that address those relationships, differences in outcomes cannot be attributed to treatment alone. The record does not report an adjusted analysis or a statistical plan describing how such issues were handled.

Even a comparison between groups in an observational study would require care. Group membership may reflect clinical circumstances, prior treatment, or other factors associated with outcomes. Statistical adjustment can address measured differences only to the extent that relevant variables are recorded and appropriately modeled. It cannot guarantee removal of confounding from unmeasured factors. The record does not describe a comparison group or such adjustment.

How should threshold outcomes be understood?

A threshold outcome is easy to communicate but compresses information. The primary outcome distinguishes participants who achieve at least the stated reduction from those who do not. It does not preserve the magnitude or pattern of change within each category. A participant just meeting the threshold is counted with someone whose reduction is larger, while a participant narrowly missing the threshold is grouped with one whose reduction is much smaller. This is a general feature of dichotomizing a continuous measure, not a result specific to this study.

The named secondary measures broaden the clinical description. The percentage reaching iPTH less than or equal to 300 pg/mL is another threshold-based outcome. Time to that level is a time-to-event outcome: it concerns when the specified event occurs, and a complete analysis may need to account for participants who do not reach the threshold during observation. The registry record does not report the results or analysis details for this measure. The hypercalcemia outcome uses a definition requiring corrected serum calcium > 11.0 mg/dL at two consecutive measurements. Requiring consecutive measurements distinguishes a repeated finding from an isolated measurement, but the registry record does not give its observed frequency.

What does missingness mean for interpretation?

The record says the full analysis set included 175 participants and that one participant was excluded from the analysis due to missing data. It does not explain the missing-data mechanism, whether additional data were incomplete, or whether any imputation or sensitivity analysis was used. In general, missingness can affect an estimate if participants with unavailable outcomes differ systematically from those with observed outcomes. The direction and size of any effect cannot be determined without more information. The stated exclusion should be reported as part of the analysis-population description, not treated as evidence that missing data could not affect the result.

What can the safety counts establish?

Safety counts describe the events recorded in the study population. They are not, by themselves, estimates of excess risk caused by the intervention. A causal safety comparison would require an appropriate comparator and a defined analysis. Serious adverse event counts also do not convey the timing, duration, severity within categories, or relationship to treatment unless those details are reported. The registry lists serious-event terms and percentages, but does not report uncertainty intervals or a comparison that would quantify relative risk.

Over-dispersion is a general statistical concern when event counts vary more than a model assumes. If a count model assumes less variability than the data contain, uncertainty can be understated. This consideration is relevant to analyses of counts, but the registry record does not report a count model or an analysis of event rates. No conclusion about the use of such methods can be drawn from the listed safety counts.

The record does not report a statistical analysis plan, multiplicity procedure, sample-size justification, or interim-analysis plan. It is therefore not possible to determine from the registry whether any particular model, adjustment, or error-control strategy was planned or used. These omissions constrain interpretation; they do not establish that a method was or was not used outside what the registry reports.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("End Stage Chronic Kidney Disease")
n      <- c(174)
events <- c(101)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  End Stage Chronic Kidney Disease  174  101  58.0  50.3  65.5  50.6  65.1  50.6  65.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome and three secondary outcomes. The primary measure is the percentage achieving at least a 40% reduction in iPTH from baseline through 12 months. The secondary measures concern achievement of iPTH less than or equal to 300 pg/mL, time to that iPTH level, and clinically meaningful hypercalcemia defined by corrected serum calcium > 11.0 mg/dL at two consecutive measurements. The record does not report results for these outcomes.

When a study evaluates several outcomes, the chance of obtaining at least one apparently unusual result can increase if each is tested separately without accounting for the number of tests. In general, multiplicity procedures may be used to manage that issue, or results may be presented as exploratory. The registry record does not report whether any multiplicity adjustment or hierarchy among outcomes was planned. It also does not report a statistical analysis plan, so the intended inferential status of the secondary outcomes is not stated.

For the primary analysis population, the record says that the full analysis set included 175 participants and that one participant was excluded from analysis due to missing data. It does not explain why the data were missing, whether the participant’s missingness was related to outcome status, or how missingness was assessed. It does not report imputation or sensitivity analyses. In general, excluding participants with missing outcome information can bias an estimate if their outcomes differ systematically from those observed; the available record does not establish whether that concern applies in this study.

The registry also does not state whether analyses used additional populations, how protocol deviations were handled, or whether missing values occurred in secondary outcomes. Those details are not reported in the registry record. The documented analysis-set information is therefore useful but insufficient to assess the robustness of the reported outcome estimates, which themselves are not reported.

12. 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: pericardial effusion (1.1%), cerebrovascular accident (1.1%), cardiopulmonary arrest (0.6%), hypertension (0.6%), myocardial infarction (0.6%).

The registry reports 181 participants at risk for serious adverse events and 15 affected in that category. It separately reports 181 at risk for other adverse events and 20 affected in that category. These are the record’s category-specific counts; they should not be added together because the record does not state whether participants could appear in both categories or how the categories relate at the participant level.

The listed serious-event terms and percentages are pericardial effusion, 1.1%; cerebrovascular accident, 1.1%; cardiopulmonary arrest, 0.6%; hypertension, 0.6%; myocardial infarction, 0.6%; and pulmonary edema, 0.6%. The registry record does not provide uncertainty intervals for these percentages or explain the denominator used for each term. The listed terms should therefore be read as reported descriptive safety information, not as a comparative estimate of risk.

These counts do not establish that an event was caused by paricalcitol. The study is observational and the record does not identify a like-for-like control group for safety comparison. The registry record does not report deaths. It also does not provide further details on event timing, duration, treatment relationship, or how event coding and attribution were handled. The counts describe recorded events in the study, not a causal safety contrast.

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

The study addresses outcomes during routine clinical use of intravenous paricalcitol in people undergoing hemodialysis for end stage chronic kidney disease. Its stated primary endpoint is the percentage achieving at least a 40% reduction in iPTH from baseline through 12 months. That endpoint definition clarifies the intended measure and timeframe, but the registry record does not report the observed percentage. The record therefore does not establish how frequently the primary outcome occurred.

The record also does not report results for the secondary outcomes: reaching iPTH less than or equal to 300 pg/mL, time to reach that level, or clinically meaningful hypercalcemia as defined by corrected serum calcium > 11.0 mg/dL at two consecutive measurements. Without these results, it is not possible to describe the observed patterns for those measures. Definitions alone are not evidence that an outcome occurred at any particular frequency or time.

Because the study is observational and no like-for-like control comparison is identified, the results, if reported, would primarily describe outcomes among the participants assessed in routine practice. Such observations could not by themselves show what would have happened to the same population under another treatment. The registry does not state allocation, and it does not report a statistical plan that would permit assessment of adjustment for potential differences or other sources of bias.

The safety counts provide descriptive information: the registry lists 15 participants affected by serious adverse events and 20 in the other adverse event category, with 181 at risk in each category. The serious-event terms are accompanied by percentages, but there is no comparative safety estimate or uncertainty interval reported. These data cannot establish whether any event was caused by the intervention, nor do they establish safety relative to another treatment.

Accordingly, the record’s contribution is chiefly to document the study’s post-marketing observational purpose, population, intervention, outcome definitions, and selected adverse-event counts. It does not provide the outcome estimates needed to determine the observed primary endpoint frequency or the secondary outcome results. No claim that treatment did or did not work follows from the information reported in the registry.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between a well-defined outcome and a reported outcome. The registry specifies a threshold, a baseline reference, and a follow-up timeframe for the primary endpoint: at least a 40% reduction in iPTH from baseline through 12 months. Those details make the intended measure understandable. Yet without the resulting percentage and its precision, readers cannot judge how often participants met the endpoint or how variable the estimate may be.

The observational design also matters. Post-marketing studies can describe outcomes in routine clinical use, which is the stated purpose of this study. However, the absence of a like-for-like control comparison means that descriptive outcome information cannot be interpreted as a randomized treatment effect. This distinction is essential when reading clinical evidence: an outcome observed after treatment is not automatically an outcome caused by treatment.

The record provides several safety counts and serious-event terms, but event counts need context. A count does not quantify comparative risk, establish causation, or show the precision of an estimate. Denominators, event definitions, follow-up, and a comparator all influence how safety information can be interpreted. The record’s counts are useful descriptive information, but they do not answer a causal comparative safety question.

Finally, the analysis population and missing-data note illustrate why transparent reporting matters. The record says the full analysis set included 175 participants and that one participant was excluded due to missing data, but does not describe the missingness mechanism or analysis strategy. Such details affect confidence in an estimate. In this case, the primary estimate is not reported, further limiting interpretation. The study’s statistical importance therefore lies in both its real-world observational context and the substantial boundaries the registry record places on inference.

15. 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 main limitation for interpreting this study is that the registry record does not report the primary outcome result. It defines the endpoint and timeframe, but gives no observed percentage, confidence interval, or test result. Results for the named secondary outcomes are also not reported. The record therefore cannot support a quantitative assessment of the study’s efficacy outcomes.

The design is observational, and allocation is not stated. The registry does not identify a like-for-like control group. This prevents a direct randomized comparison and limits causal interpretation of any outcomes observed among participants receiving paricalcitol. The record does not describe adjustment methods or other approaches that might address confounding, so their use cannot be assessed.

Information about missing data is limited. The full analysis set is described as including 175 participants, with one participant excluded from analysis due to missing data. The record does not explain the nature of the missing data, how missingness was assessed, or whether sensitivity analyses were conducted. It also does not state whether other outcome measures had missing observations.

The registry record does not report a statistical analysis plan, sample-size justification, interim-analysis plan, or multiplicity procedure. It does not provide confidence intervals for the primary endpoint or listed safety terms. These omissions make it difficult to assess precision, planned inferential priorities, and the handling of multiple outcomes.

Safety information is also limited to category counts and selected serious-event terms with percentages. The record does not report deaths, event timing, attribution to treatment, or a comparative safety analysis. These limitations are specific to the information recorded and should not be interpreted as proof that such details were absent from all study materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Zemplar iv in Patients With End Stage Chronic Kidney Disease, Undergoing Haemodialysis — NCT01084538.
• Registry record last updated 2011-09-21; status last verified 2011-09.
• Results first posted 2011-09-12.
• 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.

19. Record Summary

NCT01084538 is a completed post-marketing observational study of intravenous Zemplar (paricalcitol) in people with end stage chronic kidney disease undergoing hemodialysis. The study description names Croatia and Serbia, and the official title describes a one-year, multicountry, multicenter study. The recorded start is 2007-09, primary completion is 2010-06, and enrollment is 181.

The primary outcome was the percentage achieving at least a 40% reduction in iPTH from baseline through 12 months. The registry states that the full analysis set included 175 participants and that one participant was excluded due to missing data. The observed primary result is not reported in the registry record. Three secondary outcomes are specified, but their results are not reported.

The record lists 15 participants affected by serious adverse events and 20 in the other adverse event category, with 181 at risk in each category, along with selected serious-event terms and percentages. No like-for-like control comparison is identified, and allocation is not stated. The registry record does not report a statistical analysis plan or deaths.