This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ZS) Among Patients With S-K ≥5.8 (NCT03337477), a randomized phase 2 study. The primary outcome is Mean Absolute Change in S-K From Baseline Until 4h After Start of Dosing With SZC/Placebo.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03337477 |
| Phase | Phase 2 |
| Condition | Hyperkalemia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 70 |
| Arms in the primary outcome | 2 |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
The trial enrolled patients presenting with hyperkalemia and serum potassium at least 5.8 mmol/L. The registry describes the primary analysis population as all randomized patients, but says patients without baseline or post-baseline data were excluded from that analysis: one patient in each group. More detailed eligibility criteria, including other clinical characteristics required for enrollment, are not reported in the registry record.
Intervention
The intervention was sodium zirconium cyclosilicate, also called SZC or ZS in the record, at a dose of 10g, added to insulin and glucose. The brief study description says ZS 10g could be administered up to three times over 10h. The arm description identifies insulin and glucose as the standard of care used alongside the assigned study treatment.
Comparator
The comparator was placebo added to insulin and glucose. Thus, the randomized contrast was between adding SZC and adding placebo to the insulin-and-glucose treatment regimen. The record does not report a specific allocation ratio or further details about the timing and administration of the insulin and glucose regimen.
Primary question
The primary endpoint was the mean absolute change in serum potassium from baseline until 4h after the start of SZC or placebo dosing. The study therefore asked whether the observed potassium change over that timeframe differed in the context of the assigned add-on treatment. The registry posts an adjusted mean and confidence interval for each arm, but no estimable two-arm comparison or p-value is reported. The posted arm-specific results should not be read as a definitive test of a treatment difference.
3. Trial Design
ENERGIZE, registered as NCT03337477, was a phase 2, multicenter, randomized, double-blind, placebo-controlled study with a parallel-group design. The registry also describes the masking as triple. Which specific groups of people were masked is not reported in the registry record. The study is marked completed, with enrollment of 70 participants.
Participants were assigned to SZC 10g plus insulin and glucose or placebo plus insulin and glucose. The brief description states that SZC could be given up to three times over 10h. The registry identifies insulin and glucose as standard of care for serum potassium at least 5.8 mmol/L. It does not provide a detailed dosing schedule for insulin and glucose, nor does it explain how the permitted SZC administrations were selected in practice.
The primary outcome uses potassium measurements from baseline to 4h after dosing began. Its analysis was a regression-adjusted estimate rather than a simple comparison of unadjusted arm averages. The model included treatment group, baseline serum potassium, time from the start of insulin dosing to the start of SZC or placebo dosing, and the dose of the first insulin course in units/kg.
The posted primary results include 32 participants in the SZC arm and 36 in the placebo arm. The registry states that one patient in each group had no baseline or post-baseline data and was excluded from the analysis. The reason for the difference between enrollment and the primary-analysis counts is not further explained. The planned allocation ratio, the method used to generate the random sequence, and the sample-size justification are not reported in the registry record.
The record lists six secondary outcomes in addition to the primary outcome. They concern response criteria, potassium thresholds and normokalaemia at specified follow-up times, additional potassium-lowering therapy, and mean potassium change at earlier times. Results for those secondary outcomes are not included in the registry record for this analysis. The registry record does not report a study-specific interim-analysis plan or a detailed statistical analysis plan.
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: Patients with S-K ≥5.8 mmol/L for whom treatment with insulin and glucose to manage hyperkalaemia has been determined medically appropriate by the Investigator. The study originally recruited patients with S-K ≥6.0 mmol/L; however, this inclusion criterion was updated during CSP Amendment to allow enrolment of patients with S-K ≥5.8 mmol/L.
Overall Study
| Stage | Sodium Zirconium Cyclosilicate (SZC) 10g | Placebo |
|---|---|---|
| STARTED | 33 | 37 |
| COMPLETED | 22 | 24 |
| NOT COMPLETED | 11 | 13 |
Reasons for not completing this period:
| Reason | Sodium Zirconium Cyclosilicate (SZC) 10g | Placebo |
|---|---|---|
| not categorized into the listed ones | 11 | 9 |
| Withdrawal by Subject | 0 | 1 |
| Death | 0 | 1 |
| Lost to Follow-up | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set: all randomized patients. However, patients with no baseline or/and post-baseline data (one patient in each group) were excluded from the analysis.
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.
| Characteristic | Unit | Sodium Zirconium Cyclosilicate (SZC) 10g | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 33 | 37 | 70 | |
| Age, Continuous | years | 62.0 (SD 12.7) | 56.4 (SD 14.4) | 59.0 (SD 13.8) |
| Age, Customized: <50 years | Participants | 6 | 11 | 17 |
| Age, Customized: >=50 - <65 years | Participants | 11 | 18 | 29 |
| Age, Customized: >=65 years | Participants | 16 | 8 | 24 |
| Sex: Female, Male: Female | Participants | 16 | 19 | 35 |
| Sex: Female, Male: Male | Participants | 17 | 18 | 35 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 6 | 10 | 16 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 27 | 27 | 54 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 11 | 9 | 20 |
| Race (NIH/OMB): White | Participants | 22 | 26 | 48 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
| Region of Enrollment: Denmark | Participants | 0 | 2 | 2 |
| Region of Enrollment: Italy | Participants | 1 | 1 | 2 |
| Region of Enrollment: Russia | Participants | 13 | 14 | 27 |
| Region of Enrollment: United States | Participants | 19 | 20 | 39 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Absolute Change in S-K From Baseline Until 4h After Start of Dosing With SZC/Placebo, measured over Baseline to 4h potassium measurements..
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | mmol/L |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean absolute change in serum potassium from baseline until 4h after the start of SZC or placebo dosing, measured in mmol/L. An absolute change expresses the follow-up measurement relative to the participant’s baseline measurement, rather than reporting only the potassium concentration at follow-up. Negative estimates indicate a mean decrease from baseline; they do not, by themselves, quantify a randomized difference between the two groups.
Using change from baseline can account for the fact that participants may begin with different potassium concentrations. The registry’s analysis also adjusts for baseline potassium and other listed covariates. This produces a least-squares mean for each treatment group, intended to represent the model-adjusted mean change after accounting for those variables. The endpoint therefore summarizes an early biochemical change over a defined interval, rather than a later clinical outcome.
The registry describes the primary outcome as a continuous measure and reports a 95% confidence interval around each arm’s least-squares mean. Those intervals communicate uncertainty around the arm-specific estimates. They are not themselves a confidence interval for the treatment contrast. A direct comparison of the treatment groups, including its estimated difference and uncertainty, is not reported as an estimable result in the record. The endpoint is one part of the trial’s assessment; its numerical values alone do not establish a broader clinical effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For SZC 10g plus insulin and glucose, the reported least-squares mean change in serum potassium through 4h was -0.41 mmol/L, with a 95% confidence interval from -0.63 to -0.19. For placebo plus insulin and glucose, the corresponding least-squares mean change was -0.27 mmol/L, with a 95% confidence interval from -0.48 to -0.07. The analyzed counts were 32 and 36, respectively. Both arm-specific estimates are negative, indicating that the model-estimated mean potassium measurement decreased from baseline in each group over the endpoint timeframe.
These are adjusted estimates for each arm, not the estimated difference between arms. The record explicitly indicates that values are missing or not estimable for a two-arm comparison of this continuous outcome. No treatment contrast, confidence interval for that contrast, or p-value is reported. The arm estimates therefore describe the observed pattern and its precision within each group, but do not quantify the uncertainty around a randomized between-group effect.
A confidence interval gives a range of values compatible with the data and the statistical model under the method used. Its width conveys precision: a narrower interval would indicate more precise estimation than a wider one. Here, each interval is attached to its own arm’s least-squares mean. It should not be repurposed as an interval for the difference between SZC and placebo. Nor does an interval for one arm answer whether the groups differ from one another.
The adjustment matters when reading the estimates. The least-squares means came from a linear regression model that included treatment group, baseline potassium, the timing between insulin and study-drug dosing, and the first insulin-course dose in units/kg. The estimates are therefore conditional on the specified model and covariates, rather than raw averages calculated only from the arm counts. The registry does not report model diagnostics, the handling of any departures from model assumptions, or further details about the exact estimation procedure.
The results are limited to the defined four-hour potassium-change outcome and the available primary-analysis data. They do not, on their own, establish how participants fared at later times, whether further potassium-lowering therapy was needed, or whether any clinical outcome differed. Although the registry lists related secondary outcomes, their results are not reported in the record for this analysis. The appropriate statistical reading is consequently descriptive and cautious: arm-specific decreases were estimated, but the registry does not provide an estimable direct comparison for the primary continuous endpoint.
9. Statistical Methods Explained
The primary analysis uses a least-squares mean from a linear regression model and attaches a 95% confidence interval to each group estimate. These methods are intended to summarize a continuous endpoint while accounting for measured covariates specified in the model. The registry identifies the endpoint as absolute change in serum potassium at 4h and names the adjustment variables, but does not report a fuller statistical analysis plan or diagnostics.
What does a least-squares mean represent?
A least-squares mean is a model-based estimate of a group mean after accounting for variables included in the regression. In this trial, the model included treatment group, baseline serum potassium, the time from the start of insulin dosing to the start of SZC or placebo dosing, and the dose of the first course of insulin in units/kg. The goal of adjustment is to estimate arm-specific outcome means while incorporating those covariates, rather than simply averaging observed changes without adjustment.
The estimate depends on the model and the data used to fit it. A least-squares mean is not automatically a raw sample average, and it should not be treated as an estimate free of assumptions. The registry does not report whether covariates were centered, how missing covariate values were handled, or whether model diagnostics were conducted. Those details are not reported in the registry record.
Why adjust for baseline and treatment timing?
In general, adjusting for a baseline measure can account for differences in starting values when the outcome is a change from baseline. Including timing and insulin dose makes the estimates conditional on those recorded aspects of treatment. That can be useful when the timing or amount of insulin differs across participants, but interpretation remains tied to the variables and functional form used in the fitted model. The record lists these covariates; it does not explain why each was selected or whether any additional variables were considered.
General statistical caution applies to regression adjustment: estimates rely on the model representing the relationship between the outcome and its covariates adequately. The record does not report residual checks, sensitivity analyses, or other assessments of model fit. It is therefore possible to describe the stated model and its adjusted estimates, but not to evaluate the adequacy of its assumptions from the registry information alone.
How should the confidence intervals be read?
A confidence interval expresses uncertainty around an estimated quantity under the method used. In repeated applications of a method under its assumptions, intervals constructed in this way are designed to cover the target value at the stated confidence level. For an individual analysis, it is not a probability statement that the fixed true value lies within the particular interval. The reported 95% intervals are associated with the arm-specific least-squares means.
The intervals describe the precision of those means, not the precision of a comparison between treatment groups. A direct treatment contrast would require its own estimate and uncertainty, which are not available as an estimable result for this endpoint in the record. It is not valid to substitute a visual comparison of two arm-specific intervals for a formal contrast. No p-value for the primary treatment comparison is reported.
What does the planning illustration describe?
General sample-size planning asks how many participants would be needed under stated assumptions to detect a specified effect with a chosen operating target. The record describes the planning illustration as using the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; it also describes planning for stated fractions of the observed effect. Such figures are planning illustrations, not observed power and not evidence about the probability that the trial detected an effect.
The illustration is distinct from the trial’s original design justification. The sample-size justification used for planning the completed trial is not reported in the registry record. Actual values for the planning illustrations are not included in the registry record, so no numerical sample-size conclusion can be drawn from them. In general, planning calculations are sensitive to assumptions about the effect, variability, allocation, and statistical method. They should not be mistaken for observed participant outcomes or for a substitute for the actual treatment-effect estimate and its uncertainty.
Why can over-dispersion matter in other analyses?
General explanation: over-dispersion occurs when count data vary more than a statistical model expects. If the model understates that variability, uncertainty estimates can be too small and statistical tests can appear more conclusive than the data warrant. This is a general issue in analyses of counts or event rates; it is not a feature established for this continuous potassium-change endpoint. The primary endpoint is analyzed as a continuous measure, and the registry does not report an over-dispersion assessment for it.
The registry lists zero posted analyses for the secondary outcomes in the record. Without those analyses, readers cannot assess the results of the secondary thresholds or response definitions, their uncertainty, or how any testing across outcomes was handled. The detailed statistical methods for those outcomes are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six secondary outcomes alongside the primary outcome. They include a response definition combining potassium thresholds and restrictions on additional therapy, normokalaemia at specified follow-up times, several potassium threshold outcomes, additional potassium-lowering therapy, and mean change at earlier measurements. The record reports no posted analyses for these secondary outcomes in the information.
When a study evaluates multiple outcomes or multiple timepoints, the chance of obtaining at least one apparently unusual result can increase if each is tested separately without accounting for the multiplicity. General approaches include prespecifying a testing hierarchy or adjusting inference across tests. The registry record does not report whether any multiplicity strategy was planned or used. Without posted secondary analyses and a stated strategy, no conclusion about multiplicity-adjusted secondary evidence can be made.
The record defines the primary analysis population as the full analysis set of all randomized patients, but also states that patients with no baseline or/and post-baseline data were excluded: one patient in each group. Thus, the reported endpoint analysis did not include every randomized participant. The missing-data mechanism, reasons for the unavailable measurements, and any imputation or sensitivity-analysis methods are not reported in the registry record.
Missing outcomes can affect both the analyzed sample and the interpretation of estimates, particularly if the availability of measurements is related to participant characteristics or outcomes. That is a general concern, not evidence that missingness biased these results. The registry’s description allows the exclusion to be identified but does not establish whether the missing observations were similar to or different from the observed ones. The analysis population should therefore be understood as the randomized group with the required baseline and post-baseline data for this endpoint, as described in the record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (SZC) 10g (0-24h) | 1 | 29 | 3.4% |
| Placebo (0-24h) | 2 | 33 | 6.1% |
| Sodium Zirconium Cyclosilicate (SZC) 10g (After 24h) | 2 | 29 | 6.9% |
| Placebo (After 24 h) | 3 | 33 | 9.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sodium Zirconium Cyclosilicate (SZC) 10g (0-24h) | 0 of 29 |
| Placebo (0-24h) | 1 of 33 |
| Sodium Zirconium Cyclosilicate (SZC) 10g (After 24h) | 0 of 29 |
| Placebo (After 24 h) | 0 of 33 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sodium Zirconium Cyclosilicate (SZC) 10g (0-24h) | 4 of 29 |
| Placebo (0-24h) | 5 of 33 |
| Sodium Zirconium Cyclosilicate (SZC) 10g (After 24h) | 3 of 29 |
| Placebo (After 24 h) | 0 of 33 |
Most frequent serious adverse event terms
| Event term | Organ system | Sodium Zirconium Cyclosilicate (SZC) 10g (0-24h) | Placebo (0-24h) | Sodium Zirconium Cyclosilicate (SZC) 10g (After 24h) | Placebo (After 24 h) |
|---|---|---|---|---|---|
| Hyperkalaemia | Metabolism and nutrition disorders | 0 of 29 | 0 of 33 | 0 of 29 | 2 of 33 |
| Hypotension | Vascular disorders | 0 of 29 | 1 of 33 | 0 of 29 | 0 of 33 |
| Clonic convulsion | Nervous system disorders | 0 of 29 | 1 of 33 | 0 of 29 | 0 of 33 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 0 of 29 | 1 of 33 | 0 of 29 | 0 of 33 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 29 | 0 of 33 | 0 of 29 | 0 of 33 |
| Pneumonia | Infections and infestations | 0 of 29 | 0 of 33 | 0 of 29 | 1 of 33 |
| Cardiac failure | Cardiac disorders | 0 of 29 | 0 of 33 | 1 of 29 | 0 of 33 |
| Tibia fracture | Injury, poisoning and procedural complications | 0 of 29 | 0 of 33 | 1 of 29 | 0 of 33 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sodium Zirconium Cyclosilicate (SZC) 10g (0-24h) | Placebo (0-24h) | Sodium Zirconium Cyclosilicate (SZC) 10g (After 24h) | Placebo (After 24 h) |
|---|---|---|---|---|---|
| Hypoglycaemia | Metabolism and nutrition disorders | 4 of 29 | 3 of 33 | 0 of 29 | 0 of 33 |
| Nausea | Gastrointestinal disorders | 1 of 29 | 2 of 33 | 2 of 29 | 0 of 33 |
| Procedural pain | Injury, poisoning and procedural complications | 0 of 29 | 0 of 33 | 2 of 29 | 0 of 33 |
Serious events with the highest arm-level rate: hyperkalaemia (6.1%), gastrointestinal haemorrhage (3.4%), cardiac failure (3.4%), tibia fracture (3.4%), hypotension (3.0%).
The registry reports serious adverse events for distinct periods. During 0-24h, the SZC group lists 1 serious adverse event among 29 participants at risk, and the placebo group lists 2 among 33 at risk. After 24h, the corresponding counts are 2 among 29 and 3 among 33. These are the counts and denominators stated for each period; they should not be combined into a single period-specific rate without further information about follow-up and participant overlap.
The record lists deaths as 0 for SZC and 1 for placebo during 0-24h, and 0 for each group after 24h. It also reports other adverse-event counts of 4 among 29 and 5 among 33 during 0-24h, followed by 3 among 29 and 0 among 33 after 24h. These figures are descriptive counts, not a formal comparison of risk.
The listed serious-event terms and percentages include Hyperkalaemia, 6.1%; Gastrointestinal haemorrhage, 3.4%; Cardiac failure, 3.4%; Tibia fracture, 3.4%; Hypotension, 3.0%; and Clonic convulsion, 3.0%. The record does not provide treatment-group attribution for these terms in the registry record. Counts alone do not establish that a treatment caused an event or that a difference between groups is meaningful. Definitions, event-level details, and a statistical comparison of safety outcomes are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted primary results describe model-adjusted mean potassium decreases from baseline in each treatment group through 4h. The estimated decrease was -0.41 mmol/L for SZC plus insulin and glucose and -0.27 mmol/L for placebo plus insulin and glucose. The confidence intervals indicate uncertainty around those separate arm estimates. The registry does not report an estimable treatment contrast for this continuous outcome, so the figures do not quantify the difference attributable to adding SZC.
This distinction matters because the trial was randomized, but the available result is not a reported randomized comparison with an estimate and uncertainty for the contrast. Separate means can describe each group, but the clinical question about the difference between assigned regimens is answered most directly by the between-group estimate. That estimate, its confidence interval, and a p-value are not reported as estimable results in the record. The posted values therefore cannot establish whether the groups differed statistically or by how much.
The result concerns one biochemical endpoint at a specified early time. It does not establish a later potassium response, the need for additional treatment, or a patient-centered clinical outcome. The registry’s secondary-outcome list includes measures relevant to response and additional potassium-lowering therapy, but their results are not reported in the record. Nor do the primary estimates establish a general safety profile; safety counts are descriptive and require their own context.
General interpretation: statistical evidence and clinical importance are related but distinct. An estimate may be precise yet not address outcomes that matter beyond the measured endpoint, while an uncertain estimate may leave a range of possible effects. Here, the arm-specific confidence intervals convey precision for the adjusted means, but the missing direct contrast leaves the central comparative question unresolved by the posted primary results.
The appropriate conclusion is limited to what is reported: the adjusted mean change was negative in each arm, with the stated intervals, among the participants included in the analysis. It is not appropriate to turn those arm-specific observations into a claim that one regimen is better, worse, effective, ineffective, or equivalent. The registry record does not report enough comparative information to support such a conclusion for the primary endpoint.
13. Why This Trial Matters Statistically
This trial raises a central issue in reading randomized studies: descriptive estimates within each arm are not the same as an estimate of the randomized treatment effect. The registry reports adjusted potassium-change means for SZC and placebo groups, each with a confidence interval. Those values show the pattern of change within the groups, but the main comparative question concerns the difference between assigned regimens. A direct estimate and its uncertainty are not reported as an estimable result for the primary continuous endpoint.
The distinction is important even when an endpoint is clinically relevant and measurements are taken at a clearly defined time. An analysis should match the scientific question: for a randomized comparison, the treatment contrast is ordinarily the quantity needed to assess differences between assigned groups. Arm-specific means can support description, but they cannot by themselves supply that contrast. This is why reporting the estimate, its confidence interval, and the analysis population is essential to interpretation.
The trial also illustrates how adjustment changes the nature of a reported mean. Its primary outcome uses a regression model with baseline potassium, treatment group, insulin-to-study-drug timing, and first-course insulin dose. Readers need to distinguish such model-adjusted estimates from unadjusted averages and to understand which variables were included. The registry names the covariates, while details such as diagnostics and sensitivity analyses are not reported.
Finally, the record includes multiple secondary outcomes and a limited description of missing observations. Their analysis results, multiplicity approach, and missing-data methods are not reported. These omissions do not negate the posted primary arm estimates, but they narrow what can be concluded from the registry record. Statistically careful reading keeps the observed data, the model-based estimates, and the unanswered comparative questions distinct.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for interpretation is that no estimable two-arm comparison is reported for the continuous primary endpoint. The arm-specific least-squares means and their confidence intervals do not give a direct treatment-effect estimate. No p-value or confidence interval for the between-group contrast is reported. This prevents a direct assessment of the magnitude and precision of the randomized comparison from these results.
The analysis excluded one patient in each group because of no baseline or/and post-baseline data, although the registry describes the target population as all randomized patients. The record does not report why these measurements were unavailable, how missingness was handled beyond exclusion, or whether sensitivity analyses were performed. This leaves uncertainty about the consequences of missing endpoint data.
The registry lists six secondary outcomes but no posted analyses for them in the information. It also does not report how multiplicity was addressed, whether interim analyses were planned, or the original sample-size justification. Those omissions limit assessment of the full analysis plan and the context for interpreting secondary findings.
The record describes a regression model and its covariates but does not report model diagnostics, sensitivity analyses, or additional estimation details. It also gives limited detail about participant eligibility, allocation procedures, treatment administration, and the identities of groups covered by triple masking. Finally, the safety information is presented as counts for specified periods and selected event terms; further event-level details and formal comparative analyses are not reported. These limitations define the scope of interpretation rather than proving that the estimates are biased or that the study was poorly conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ZS) Among Patients With S-K ≥5.8 — NCT03337477.
- Registry record last updated 2020-01-28; status last verified 2020-01.
- Results first posted 2020-01-28.
- 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.
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18. Record Summary
NCT03337477, ENERGIZE, was a completed phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study with triple masking. It enrolled 70 participants with hyperkalemia and compared SZC 10g plus insulin and glucose with placebo plus insulin and glucose. The primary outcome was mean absolute change in serum potassium from baseline through 4h.
The registry reports adjusted mean changes of -0.41 mmol/L (95% CI -0.63 to -0.19) for SZC and -0.27 mmol/L (95% CI -0.48 to -0.07) for placebo. The analysis included 32 and 36 participants, respectively, after one patient in each group without baseline or/and post-baseline data was excluded. A direct two-arm comparison for this continuous endpoint is not reported as estimable. Results for the listed secondary outcomes and the study-specific multiplicity and missing-data methods are not reported in the registry record.