The ORTIZ Study: Optimising RASi Therapy With SZC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The ORTIZ Study: Optimising RASi Therapy With SZC (NCT04983979), a randomized phase 2 study. The primary outcome is Proportion of Patients on Maximum Dose (300mg) Irbesartan Therapy at 12 Weeks Compared to Placebo.

2. Clinical Question

The clinical hypothesis recorded for the study was that treatment with SZC versus placebo would enable maximisation of RASi therapy, specified as irbesartan, in patients with diabetic kidney disease. The primary endpoint focuses on the proportion reaching the maximum irbesartan dose, rather than on a direct measure of kidney function or potassium change. The registry also lists secondary outcomes concerning potassium, blood pressure, GFR and adverse events.

The registry record does not report a primary-outcome result, so it does not establish the observed proportions on maximum-dose irbesartan or the difference between arms. It also does not report a confidence interval or a significance test for that endpoint. The question is therefore clear from the endpoint description, but its answer cannot be read from the recorded information.

3. Trial Design

The ORTIZ Study is described as a phase 2, randomized, parallel-group, placebo-controlled trial with quadruple masking. It compares sodium zirconium cyclosilicate (SZC) with matched placebo. The registry lists an enrollment of 18. Randomization and masking describe important design features, but the registry record does not report the method used to generate the allocation sequence, the allocation concealment procedure, or which roles were included in the quadruple masking.

The planned treatment period was 3 months. In both arms, the recorded dose options were 5 or 10g once daily, with titration according to potassium levels measured at clinic visits. The primary endpoint is assessed at study end (week 12) and concerns whether patients were on maximum-dose irbesartan therapy (300mg). The trial hypothesis was that SZC would enable optimisation of RASi therapy in patients with diabetic kidney disease.

The registry lists the study status as terminated. The recorded start date is 2022-06-17 and the primary completion date is 2023-03-16. The reason for termination, the timing of the termination decision, and its relationship to recruitment or data collection are not reported in the registry record. The enrollment figure alone does not establish how many patients contributed data to any particular endpoint or analysis.

Secondary outcomes include changes in potassium and blood pressure, potassium thresholds, a specified decline in GFR, change in GFR and adverse-event frequency. The registry lists eight outcome measures and eight analyses. It does not report the full statistical analysis plan or provide enough detail to determine how every outcome and analysis was defined in practice. In particular, the record does not describe the planned handling of missing observations, the analysis population, or any interim analyses.

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: After patient enrolment, patients were checked for eligibility, then randomized to either Arm A or B if eligible. 18 participants were consented for inclusion in ORTIZ. 7 participants failed screening as they did not meet the inclusion criteria. Two participants were not randomised despite being eligible. One participant was deemed to be unable to comply with the study schedule. The other was screened and found to be eligible 2 days prior to study termination so was not randomised.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Patients with diabetic kidney disease

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Total 9 participants

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Patients on Maximum Dose (300mg) Irbesartan Therapy at 12 Weeks Compared to Placebo, measured over Study end (week 12).

The primary endpoint is the proportion of patients on maximum-dose irbesartan therapy (300mg) at the end of 12 weeks, compared with placebo. The record defines the arm-specific proportion as the number of individuals on maximum-dose therapy divided by the number of individuals in that study arm. It defines the difference as the experimental-arm proportion minus the placebo-arm proportion.

This endpoint is used to assess the study’s stated aim of enabling RASi optimisation. It is a binary outcome at the participant level: each participant either is or is not on the stated maximum dose at the specified assessment. Comparing proportions gives a direct description of how often that endpoint was reached in each arm. The arm difference communicates the direction and size of the contrast on the proportion scale, when results are available.

The primary endpoint is distinct from the listed secondary measures of potassium, blood pressure and GFR. A result on maximum-dose irbesartan would not, by itself, describe those other outcomes. Nor would the endpoint alone establish how treatment affected each participant’s potassium or kidney function.

The primary endpoint description is present, but its observed arm counts, proportions and between-arm difference are not reported in the registry record. A confidence interval and significance test for the primary comparison are also not reported in the registry record. The endpoint can therefore be explained, but its estimated result and precision cannot be assessed from the recorded information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to study arms by chance according to a specified procedure. General statistical explanation: random assignment is intended to make the arms comparable, on average, with respect to both measured and unmeasured characteristics. In a trial with limited enrollment, chance imbalances can still occur, so randomization does not guarantee that the groups are identical. The registry describes the study as randomized but does not report the sequence-generation or allocation-concealment methods.

What does the primary endpoint compare?

The primary endpoint is a participant-level binary outcome: whether the participant was on maximum-dose irbesartan therapy (300mg) at study end (week 12). The registry defines a proportion for each arm and specifies the contrast as the SZC-arm proportion minus the placebo-arm proportion. General statistical explanation: a difference in proportions is an absolute contrast on the proportion scale. Its interpretation depends on the observed arm values and on a clear account of the participants included in each denominator. Those values and denominators are not reported in the registry record.

A binary endpoint can be summarized using counts and proportions. The count indicates how many participants had the recorded outcome; the proportion relates that count to the relevant group denominator. Neither can be recovered from enrollment alone. The registry’s enrollment of 18 is not a report of the number with primary-endpoint data, nor does it specify the size of either arm. No primary endpoint count, proportion, or difference is reported in the registry record.

What would a confidence interval add?

General statistical explanation: a confidence interval expresses uncertainty around an estimate. For a difference in proportions, it would indicate which differences are reasonably compatible with the observed data under the method’s assumptions. A narrow interval would indicate greater precision than a wide interval, although precision is not the same as clinical importance. A confidence interval is not reported for the primary endpoint in the registry record, so the precision of the intended comparison cannot be assessed.

A test of statistical significance addresses a different question from estimation. General explanation: a p-value measures how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It does not give the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The primary endpoint’s test statistic and p-value are not reported in the registry record. No conclusion about statistical significance can be drawn from the stated design or enrollment alone.

How should the design features be read?

The study is described as parallel-group, meaning the registry identifies separate SZC and placebo arms, and as placebo-controlled, with matched placebo listed as the comparator. It is also described as quadruple-masked. General explanation: masking is intended to limit the influence of knowledge of treatment assignment on conduct, assessment or reporting. The registry record does not identify the roles covered by the masking label or explain how masking was maintained. The presence of masking in the design description should not be mistaken for evidence about the outcome.

The recorded dosing plan allowed 5 or 10g once daily in both arms, titrated according to potassium levels at clinic visits. This is part of the treatment description; it is not a statistical result. The registry does not give treatment adherence, dose changes by arm, or participant-level exposure information. It is therefore not possible to describe how many participants received either dose or how dosing was distributed.

What do the planning illustrations mean?

General statistical explanation: a sample-size calculation estimates the amount of information a future study might need to detect a specified effect under stated assumptions. The planning assumptions recorded for the illustrations use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning illustrations computed from the observed effect, not the trial’s own design. Their values must not be interpreted as observed power, and they do not show that the trial had adequate power to detect its primary outcome.

The record does not report a sample-size justification for the trial or a prospective target based on a stated clinically meaningful effect. The actual numerical outputs of any planning illustrations are not included in the registry record. A planning calculation also cannot substitute for an observed estimate and its uncertainty, particularly when the primary outcome result is not reported.

Why do the safety counts need cautious interpretation?

General statistical explanation: event counts describe what was recorded, but small counts can be highly uncertain as estimates of an underlying event frequency. A difference between group counts is not, by itself, an adjusted comparison or a causal conclusion. Interpretation also depends on how events were defined, how long participants were observed, and whether all relevant events were collected consistently. The record provides some serious and non-serious event counts, but does not report a comparative statistical analysis or confidence intervals for them.

Over-dispersion is a general issue for count data: observed variability can exceed what a simple count model assumes. It can matter when modelling event counts, especially when participants differ in their underlying event rates or exposure time. The registry record does not report a count-data model or enough detail about exposure time to assess whether over-dispersion was considered. This is a general methodological consideration, not a description of an analysis confirmed for this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures and eight analyses. It includes a primary endpoint and secondary outcomes involving potassium, blood pressure, GFR and adverse events. When a study examines several outcomes or multiple time points, the chance of at least one apparently notable result can increase if all comparisons are treated as independent confirmatory tests. General statistical explanation: multiplicity can be addressed through a prespecified hierarchy, adjustment procedures, or by treating secondary findings as exploratory. The statistical approach used for this study is not reported in the registry record.

The registry describes the primary endpoint at study end (week 12), while the outcome list also includes change in potassium at each time point and several other outcomes. The record does not report which time points were included in the analyses, how repeated measurements were handled, or whether the primary endpoint was evaluated under a prespecified testing hierarchy. The posted analysis extraction does not reduce the primary outcome to one comparison because it involves several categories or time points. The recorded endpoint description still identifies the intended maximum-dose comparison, but its result is not reported.

Missing-data handling is not reported in the registry record. The record does not state how missing endpoint values were treated, whether any imputation was used, or what sensitivity analyses were planned or conducted. It also does not specify the analysis population, such as whether the primary analysis included all randomized participants or only participants with available endpoint data. These omissions limit assessment of how the endpoint estimate would relate to the randomized comparison.

The record does not report whether interim analyses were planned or conducted, nor does it provide the full statistical analysis plan. No assumptions about multiplicity control, missing-data methods, or analysis populations can therefore be attributed to the trial. These are areas where the registry record leaves the analytical approach unclear, rather than evidence that a particular method was or was not used.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: broken left humerus (20.0%).

The registry reports serious adverse-event counts separately for the SZC and placebo groups. In the SZC group, four participants are listed as at risk for serious events, with zero affected. In the placebo group, five participants are listed as at risk, with one affected. The record lists zero deaths in each group. For other, non-serious events, three participants are listed as affected among four at risk in the SZC group, and two among five at risk in the placebo group.

These figures are descriptive counts. They are not adjusted estimates, and the registry record does not provide confidence intervals or a statistical comparison of safety between arms. The counts should not be treated as proof that one treatment has a higher or lower underlying risk. The record does not report the duration of individual follow-up, detailed event definitions, or a complete account of the methods used to collect and classify events.

The record names “Broken left humerus” as a top serious term and reports 20.0%. That term is a safety listing; the record does not provide additional context about its timing, relationship to treatment, or circumstances. The registry’s safety information can therefore be read as a report of recorded counts and a listed term, not as a complete assessment of comparative safety.

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

The record describes a randomized, placebo-controlled trial designed to ask whether SZC could enable patients with diabetic kidney disease to reach maximum-dose irbesartan therapy. Its primary endpoint is the proportion on 300mg irbesartan at week 12, contrasted between the SZC and placebo arms. The registry does not report the primary-outcome counts, proportions, difference, confidence interval or significance test. It therefore does not provide the numerical result needed to judge the observed primary comparison.

This absence of a reported primary result should not be turned into a claim that the intervention did or did not affect the endpoint. The record does not support either conclusion. The study’s hypothesis and design describe what it sought to evaluate; they are not evidence of the outcome. Similarly, the stated status of terminated does not explain why the study ended, whether termination affected data availability, or what the results would have been under a different course of follow-up.

The reported safety counts offer limited descriptive information, but do not establish a comparative safety effect. No inferential analysis or precision estimates are reported for those counts. The secondary outcomes listed in the registry also cannot be interpreted as results: their numerical findings are not reported in the registry record.

General statistical explanation: a result is most informative when its estimate is considered alongside its uncertainty, the endpoint definition, the participants included in the analysis and the limitations of the study. Here, key elements of that interpretation—including the primary estimate, its precision, analysis population and missing-data approach—are not reported in the registry record. The study’s recorded enrollment of 18 is useful context about its scale, but it does not reveal how many participants contributed to each analysis or establish the precision of any result.

The appropriate reading is consequently narrow. The registry documents the intended question, the trial design, the endpoint definition and some safety counts. It does not document a numerical primary efficacy result or enough analytical detail to assess the planned comparison fully. These gaps limit what can be concluded from this record; they are not evidence for a particular treatment effect.

13. Why This Trial Matters Statistically

This trial raises a statistical question that depends on a clearly defined participant-level endpoint: whether patients were on maximum-dose irbesartan therapy at the end of the treatment period. The registry specifies the arm-specific proportions and the direction of the intended contrast. That definition matters because it makes clear what the primary comparison was meant to quantify, and distinguishes it from the separate outcomes concerning potassium, blood pressure, GFR and adverse events.

The record also illustrates why design labels and results must be kept separate. Randomization, placebo control, parallel groups and quadruple masking describe the intended study structure. They do not reveal the observed endpoint values, the uncertainty around them, or the consequences of the study’s terminated status. A trial can have a defined primary question while its registry record still lacks the result needed to answer it.

Enrollment of 18 provides important context for the scale of the trial, but is not a substitute for arm-specific analysis denominators. Without the number contributing endpoint data, the observed proportions and their uncertainty, a reader cannot assess the precision of the primary comparison. Likewise, reported safety counts are useful descriptive information but cannot establish a comparative safety effect in the absence of an inferential analysis and further context.

The record lists multiple outcomes and analyses, making prespecified handling of multiplicity and missing data relevant to interpretation. Those methods are not reported in the registry record. This matters because a transparent analysis plan helps readers distinguish a primary confirmatory question from secondary or exploratory findings and understand how incomplete observations were treated. The record therefore offers a useful statement of the intended clinical question, while leaving important elements of its statistical answer unresolved.

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 principal limitation for interpreting the trial is that the registry record does not report the primary endpoint result. There are no arm-specific outcome counts or proportions, no reported between-arm difference, and no confidence interval or significance test. As a result, the main clinical question is not numerically answerable from the record.

The registry lists enrollment of 18, but does not report arm-specific numbers or the number with evaluable primary-endpoint data. It does not identify the primary analysis population, explain how missing endpoint data were handled, or report sensitivity analyses. The reason for the terminated status and its implications for follow-up and data availability are also not reported in the registry record.

Although the record identifies the study as randomized and quadruple-masked, it does not describe the allocation-sequence method, concealment procedures, or which roles were masked. It does not report treatment adherence or the distribution of dose titration. These details would help readers assess implementation, but cannot be inferred from the design labels.

The registry lists multiple outcome measures and analyses, yet the statistical analysis plan and approach to multiplicity are not reported. It also does not report numerical results for the listed secondary outcomes. Safety information is limited to the recorded group counts and a top serious term; comparative uncertainty, event-collection details and participant follow-up duration are not reported in the registry record. These limitations constrain interpretation of both efficacy and safety and do not justify an inference about why the record is incomplete.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The ORTIZ Study: Optimising RASi Therapy With SZC — NCT04983979.
• Registry record last updated 2025-06-08; status last verified 2025-06.
• Results first posted 2025-06-08.
• 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.

18. Record Summary

The ORTIZ Study is a phase 2, randomized, parallel-group, placebo-controlled, quadruple-masked trial of sodium zirconium cyclosilicate versus matched placebo in patients with diabetic kidney disease. The registry lists enrollment of 18 and a treatment period of 3 months. The primary endpoint is the proportion on maximum-dose irbesartan therapy (300mg) at study end (week 12), with the comparison defined as the SZC-arm proportion minus the placebo-arm proportion.

The registry status is terminated. The recorded start date is 2022-06-17 and the primary completion date is 2023-03-16. The record lists eight outcome measures and eight analyses, but does not report the primary endpoint result or the numerical results of the listed secondary outcomes. It also does not report the analysis population, missing-data methods, or statistical plan. Some serious and non-serious adverse-event counts are recorded, but no comparative safety analysis is reported.