Effect of Pioglitazone on Insulin Resistance, Atherosclerosis Progression and Clinical Course of Coronary Heart Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Pioglitazone on Insulin Resistance, Atherosclerosis Progression and Clinical Course of Coronary Heart Disease (NCT03011775), a randomized phase 4 study. The primary outcome is Сardiovascular Death.

2. Clinical Question

The central comparison is therefore between pioglitazone added to standard care and standard care alone. The registry describes the study as randomized, with a parallel-group design and no masking. It records cardiovascular death as the primary outcome measure, while its description of the primary endpoints encompasses additional clinical events. The record does not provide a single reduced comparison covering that broader endpoint description. Nor does it report enough outcome detail to establish how the broader endpoint components were combined or analyzed.

The study also lists secondary measurements related to carotid atherosclerosis, systemic inflammation and lipid metabolism. These outcomes address biological and vascular measures alongside clinical events. The question is whether the groups differed on these measures and on clinical outcomes; the posted information does not give results for the listed secondary outcomes in the registry record used for this analysis. It therefore does not support conclusions about changes in insulin resistance, atherosclerosis progression, or lipid and inflammation measures.

3. Trial Design

The registry classifies this as a phase 4 randomized trial with a parallel design and no masking. It records enrollment of 43 participants: 20 assigned to pioglitazone plus standard care and 23 to standard care. The trial status is completed. Its recorded start is 2012-11, and primary completion is recorded as 2014-06.

The intervention description specifies pioglitazone 15 mg once daily in the morning, added to standard medical therapy. The standard-care regimen is described as isosorbide dinitrate 10-20 mg twice daily, acetylsalicylic acid 75 mg once daily, bisoprolol 2.5 mg once daily, rosuvastatin 20 mg once daily and ramipril 5 mg once daily. The record also mentions diet and lifestyle recommendations, but their content is not reported in the registry record.

The study summary describes standard complex drug therapy over 6 months. The listed timeframe for the cardiovascular-death outcome is “Baseline and 1 year.” The registry record does not explain how these timeframes relate, whether follow-up differed across outcomes, or how follow-up was handled for participants without an observed event.

The study description identifies intended primary clinical endpoints involving death due to myocardial infarction, coronary revascularization procedures, and hospitalization for acute coronary syndrome or unstable angina. In contrast, the posted primary outcome measure is the number of participants with cardiovascular death. The registry record does not reduce the primary outcome to one comparison across the stated categories or time points. That distinction limits what can be inferred from the cardiovascular-death count alone.

The record lists secondary outcomes concerning thickness of the intima-media complex, carotid stenosis diameter and lesions, systemic inflammation, and lipid metabolism. Although the registry gives a count of 17 outcome measures and 7 analyses, analytic details for those outcomes are not reported in the registry record. The record also does not report the randomization method, allocation concealment, protocol deviations, or the statistical plan. The sponsor is Ukrainian Medical Stomatological Academy.

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

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 Сardiovascular Death, measured over Baseline and 1 year.

The posted primary outcome measures the number of participants with cardiovascular death. A count of participants with an event is a binary outcome: each participant is classified according to whether the event was recorded during the specified observation period. The registry lists the timeframe as “Baseline and 1 year.” It reports zero cardiovascular deaths in the pioglitazone plus standard-care group and zero in the standard-care group.

Clinical events such as death can be important endpoints because they directly describe events experienced by participants, rather than an intermediate laboratory or imaging measure. That general rationale does not establish that this outcome was the only intended primary endpoint in this trial. The study description also names death due to myocardial infarction, revascularization, and hospitalization for acute coronary syndrome or unstable angina as intended primary points. The posted cardiovascular-death measure is narrower than that description, and the registry record does not report a combined result for the broader set of events.

With no cardiovascular deaths recorded in either group, the posted counts do not display a between-group difference for this outcome. A zero count is not evidence that the groups are equivalent: the precision of an estimate depends on the amount of information and the analysis, and no confidence interval or inferential comparison for this measure is reported in the registry record. The record also does not specify how the listed timeframe was operationalized for this outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent? The posted cardiovascular-death measure is a count of participants with an event. For a binary outcome, each participant is classified as having or not having the event under the outcome definition. Counts are easy to understand, but a comparison generally also needs to account for how many participants were observed in each group and how completely outcomes were ascertained. The registry lists 20 participants in the pioglitazone plus standard-care group and 23 in the standard-care group; it records zero cardiovascular deaths in both.

Why does a zero in each group not settle the comparison? When no events are observed, the directly observed counts do not distinguish the groups on that outcome. General statistical reasoning cautions against interpreting this as proof that the underlying event rates are exactly equal. The data may be compatible with a range of possible effects. A confidence interval is a way of expressing uncertainty around an estimated effect, under the assumptions of a specified method. No confidence interval or effect estimate for the cardiovascular-death comparison is reported in the registry record.

What would an inferential comparison add? A statistical test or interval-based analysis would need a defined estimand and method. For a binary outcome, possible estimands include a difference in event probabilities or a relative measure, while time-to-event methods may incorporate the timing of events and censoring. These are general approaches, not claims about the method used in this trial. The registry record does not report the statistical method for cardiovascular death, and the available outcome details do not identify a selected comparative estimate.

How should the timeframe be considered? The posted cardiovascular-death outcome lists “Baseline and 1 year,” while the summary describes treatment over 6 months. This leaves uncertainty about the follow-up period used for the endpoint and how it relates to the treatment period. In general, interpreting event counts requires knowing when observation began and ended, how deaths were identified, and whether all participants had comparable follow-up. Those details are not reported in the registry record.

What is the issue with the broader endpoint description? The study summary describes intended primary endpoints that include death due to myocardial infarction, coronary revascularization and hospitalization for acute coronary syndrome or unstable angina. A composite endpoint combines specified events according to a stated rule. Its result can differ from the result for any one component, and its meaning depends on definitions and analysis choices. The posted outcome measure is cardiovascular death, and the registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison. A unified result for the broader endpoint is therefore not available in the registry record.

What does the sample-size approach mean? The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration is described as detecting a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is total events using the Schoenfeld method; for other outcomes, it is participants per arm. These are planning assumptions, not the trial’s own design justification, and the sample-size values are not reported in the registry record details used. Such illustrations are not observed power and do not show that the completed trial had a particular probability of detecting an effect.

Why can event data require special care? General statistical methods for event counts can be sensitive to sparse outcomes. When events are very uncommon, approximations designed for larger counts may not describe uncertainty well. Time-to-event analyses also depend on event timing and censoring; a simple count does not contain that information. Over-dispersion, in general, means that observed variability exceeds what a chosen count model expects, and methods that account for it may be needed in some settings. The registry record does not report use of a count model, a time-to-event model, or an over-dispersion adjustment for this outcome.

What is reported about other outcomes? The registry lists 17 outcome measures and 7 analyses, with secondary outcomes covering carotid measurements, systemic inflammation and lipid metabolism. Counts of listed outcomes and analyses do not themselves describe statistical methods or results. The analysis populations, covariate adjustments, missing-data methods, multiplicity procedures and outcome-specific statistical models are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures, including cardiovascular death and secondary measures of carotid atherosclerosis, systemic inflammation and lipid metabolism. It also records 17 outcome measures and 7 analyses. When many outcomes are examined, the chance of at least one apparently notable result can increase if each is tested separately. General approaches to multiplicity include specifying a primary hypothesis in advance, adjusting significance thresholds, or interpreting secondary findings as exploratory. The registry record does not report a multiplicity strategy or explain how the listed analyses were prioritized.

Missing-data handling is not reported in the registry record. The registry entries do not describe whether all enrolled participants contributed outcome data, how incomplete follow-up was handled, or whether any participants were excluded from an analysis. These details affect the interpretation of both event counts and continuous secondary measures. No imputation method, sensitivity analysis, or missingness description is reported.

The analysis populations are also not reported in the registry record. It is not stated whether analyses followed randomized assignment, included only participants who completed treatment, or used another population definition. The registry identifies randomization but does not describe allocation concealment or deviations from assigned treatment. Those omissions prevent assessment of how the analysis preserved or departed from the randomized comparison.

The outcome description gives “Baseline and 1 year,” while the study summary describes treatment over 6 months. The record does not explain the relationship between these timeframes. Together with the absence of a reduced comparison for the broader primary endpoint description, this limits interpretation of which observations were included in each outcome analysis.

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.

The adverse-event figures record zero serious events and zero other events in both groups. The pioglitazone plus standard-care group has 20 participants at risk in each listing, and the standard-care group has 23 participants at risk in each listing. Deaths are also recorded as zero in both groups. No serious adverse-event terms are listed.

These figures should be read as the events recorded in the registry, not as proof that no adverse events occurred during the trial. The registry record does not report the method or period used to collect adverse events, the definitions applied, the completeness of reporting, or whether events were assessed for relationship to treatment. It also does not describe how repeated events in the same participant were handled.

Zero recorded events in a relatively small study leaves uncertainty about the frequency of uncommon harms. The figures do not establish equal safety between groups, and they cannot rule out events that were not observed or not captured in the posted record. The available safety information is descriptive; no comparative estimate or uncertainty interval for adverse events is reported in the registry record.

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

The posted primary-outcome figures establish a limited fact: zero participants in the pioglitazone plus standard-care group and zero in the standard-care group were recorded with cardiovascular death. This is a description of the recorded counts, not a demonstration that the treatments have equal effects or that cardiovascular death cannot occur in either group.

The trial’s broader stated clinical question includes death due to myocardial infarction, revascularization and hospitalization for acute coronary syndrome or unstable angina. The registry does not report a unified result for these events. It also does not report numerical findings for the listed secondary outcomes on carotid atherosclerosis, inflammation or lipid metabolism. The cardiovascular-death figures therefore cannot answer the full set of questions described in the study summary.

The absence of a reported effect estimate and confidence interval means the precision of a group comparison cannot be judged. General statistical interpretation distinguishes between a result that shows little estimated difference with narrow uncertainty and one that has insufficient information to rule out meaningful differences. The posted counts alone do not tell which situation applies.

The study’s enrollment was 43, and its outcome listing and treatment description leave unresolved details about follow-up, analysis populations and missing data. These limitations matter when deciding how broadly the figures can be interpreted. In particular, the record’s “Baseline and 1 year” outcome timeframe is not reconciled with the summary’s description of treatment over 6 months.

Accordingly, the result does not establish treatment benefit, lack of benefit, equivalence, or a definitive safety conclusion. It reports no cardiovascular deaths in either group and no adverse events in the posted adverse-event counts. Broader conclusions would require outcome results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because the outcome presented as primary is a sparse binary event: cardiovascular death was recorded zero times in each group. When event counts are zero, a simple visual comparison does not provide an estimate of how different the groups might be in the underlying population. The absence of a reported interval or other comparative analysis makes the uncertainty especially important to recognize.

The registry also describes a wider clinical endpoint set than the posted primary outcome measure. This distinction illustrates why endpoint definitions matter. A count for cardiovascular death is not interchangeable with a composite that includes revascularization or hospitalization. Readers need the exact endpoint definition and a reported analysis to understand what the trial evaluated and what its results address.

The study also includes multiple secondary outcomes and analyses. In general, multiple testing can make isolated findings harder to interpret unless the analysis plan specifies how outcomes are prioritized or how multiplicity is handled. The record does not report such a plan. This absence is particularly relevant when several biological and clinical outcomes are considered together.

Finally, the listed treatment duration and outcome timeframe are not aligned explicitly in the registry record. Follow-up duration, missing outcome information and analysis population are central to interpreting event data, yet these details are not reported. The trial therefore illustrates a broader statistical point: a concise event count is useful, but it cannot substitute for transparent endpoint definitions, analysis methods and uncertainty estimates.

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 registry record offers limited information for interpreting the posted cardiovascular-death count. It reports zero events in both groups but does not provide an effect estimate, confidence interval, p-value, or statistical method for this comparison. The count therefore supports description but not a precise comparative conclusion.

The primary endpoint information is not fully aligned. The study summary describes a broad set of intended clinical endpoints, including death due to myocardial infarction, revascularization, and hospitalization for acute coronary syndrome or unstable angina. The listed primary outcome measure is cardiovascular death, and the registry indicates that the primary outcome has several categories or time points without a single reduced comparison. Results for the broader endpoint are not reported in the registry record.

The registry lists the cardiovascular-death timeframe as “Baseline and 1 year,” while describing standard therapy over 6 months. It does not clarify follow-up, event ascertainment or how participants without complete follow-up were handled. The analysis populations and missing-data procedures are not reported.

The study is small, with 43 participants recorded in total, and the event count is zero in both groups. The record does not provide a sample-size justification or an explanation of the trial’s ability to estimate clinical-event effects. The planning assumptions described for sample-size illustrations should not be read as the trial’s own design rationale or as observed power.

Other limitations include the absence of reported results for the listed secondary outcomes, no reported multiplicity strategy despite multiple outcomes and analyses, and no details on randomization implementation, allocation concealment, protocol deviations or adverse-event ascertainment. These gaps restrict assessment of both the robustness and scope of conclusions from the registry data.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Pioglitazone on Insulin Resistance, Atherosclerosis Progression and Clinical Course of Coronary Heart Disease — NCT03011775.
• Registry record last updated 2022-03-10; status last verified 2022-01.
• Results first posted 2022-03-10.
• 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 registry record describes a completed, phase 4, randomized, open-label, parallel-group trial sponsored by Ukrainian Medical Stomatological Academy. Enrollment was 43, with 20 participants assigned to pioglitazone plus standard care and 23 to standard care. Pioglitazone was described as 15 mg once daily in the morning, added to a regimen that included isosorbide dinitrate, acetylsalicylic acid, bisoprolol, rosuvastatin and ramipril.

The posted primary outcome measure is the number of participants with cardiovascular death, with a timeframe listed as “Baseline and 1 year.” The recorded count is zero in each group. The registry’s study description identifies a broader set of intended primary clinical endpoints, but a single comparison for that set is not reported. Serious and other adverse-event counts are also zero in both groups.

Statistical methods, uncertainty estimates, missing-data handling, analysis populations, multiplicity procedures and numerical results for secondary outcomes are not reported in the registry record.