Rosiglitazone Versus a Sulfonylurea On Progression Of Atherosclerosis In Patients With Heart Disease And Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rosiglitazone Versus a Sulfonylurea On Progression Of Atherosclerosis In Patients With Heart Disease And Type 2 Diabetes (NCT00116831), a randomized phase 3 study. The primary outcome is Change From Baseline in Percent Atheroma Volume (PAV) to Month 18.

2. Clinical Question

The trial was designed to compare the treatments on progression of coronary atherosclerosis, using imaging of a specified coronary-artery segment. The primary measure is change in percent atheroma volume, rather than a clinical event such as a heart attack or death. The registry record identifies the endpoint and its population, but does not report the group estimates or a between-group comparison. Therefore, the posted record does not establish the direction, magnitude, or precision of any difference on the primary endpoint.

3. Trial Design

This was a Phase III, randomized, triple-masked, parallel-group, active-controlled clinical trial. The official title describes a multicenter study with an 18-month follow-up, comparing rosiglitazone with glipizide in people with type 2 diabetes mellitus and cardiovascular disease. The registry lists enrollment as 672 and status as completed. It records a start date of 2005-01 and primary completion in 2008-08.

Both groups received an oral antidiabetic medication: rosiglitazone maleate or glipizide. The record identifies the trial as active-controlled, so the comparison was between these two treatments rather than between a treatment and no active treatment. It does not report the allocation ratio, the randomization procedure, or which roles were masked. The label “triple” describes the recorded masking level, but the registry record does not identify the three masked parties.

The primary endpoint was assessed at baseline and Month 18, with an exit-imaging eligibility condition of at least 9 months in the IVUS-evaluable population. This endpoint-specific population was defined as randomized participants who received at least one dose and had evaluable baseline and exit IVUS imaging. Its size is not reported in the registry record. Enrollment is not interchangeable with the number included in this endpoint analysis, and the record does not give the analysis population count.

The record lists additional imaging outcomes involving atheroma, vessel, and lumen volume and area. It does not give the analysis plan, the methods used to estimate treatment differences, or the primary endpoint results.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: IVUS Evaluable Population (Defined as all randomized participants who received at least one dose of study medication, with an evaluable Baseline and exit \[≥ 9 months\] IVUS imaging assessment.)

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 Change From Baseline in Percent Atheroma Volume (PAV) to Month 18, measured over Baseline to Month 18.

The primary endpoint is change from baseline in percent atheroma volume (PAV) to Month 18. PAV is defined as total atheroma volume divided by total vessel volume, multiplied by 100. It was assessed by intravascular ultrasound in a 40 mm segment of non-intervened coronary arteries. The reported unit is percent, with the endpoint expressed as an absolute change.

In general, an imaging measure such as PAV provides a way to quantify atherosclerotic plaque burden in a defined artery segment. Using change from baseline focuses the comparison on how the measured value shifts over follow-up, rather than only comparing values at the end of follow-up. The vessel-volume denominator makes PAV a relative measure of plaque volume within the measured vessel segment. The record identifies this as the primary efficacy endpoint; the exact reason for choosing it over the other listed imaging measures is not reported in the registry record.

The Month 18 comparison is restricted to the IVUS-evaluable population, which requires dosing and evaluable baseline and exit imaging, with exit imaging at least 9 months after baseline. This definition matters when interpreting the endpoint: it is not automatically an estimate for every randomized participant. The registry record does not report the number analyzed, group means, variability, or the estimated between-group difference in change. Consequently, the endpoint definition can be described, but its observed result and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the primary endpoint as a continuous measure and names the mean as the parameter of interest, with standard deviation as the dispersion measure. It does not report which statistical test, regression model, or covariate adjustments were used for the primary comparison. The explanations below describe general statistical concepts; they should not be taken as a description of methods actually used in this trial unless the registry record explicitly says so.

What does a mean describe?

In general, a mean is the arithmetic average of measured values. For a change-from-baseline outcome, each participant's change is determined from the follow-up value relative to that participant's baseline value, and a group mean summarizes those changes. A between-group contrast then compares the groups' average changes. The registry record does not report the group means or the contrast, so no numerical comparison can be interpreted.

A standard deviation describes the variability of individual observations around a group mean. It is not the same as the uncertainty in the estimated mean or in the treatment contrast. In general, uncertainty in an estimate depends on both variability and the amount of information available for that analysis. The registry record does not report the endpoint analysis group sizes or a standard error for the treatment contrast.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data under a specified statistical procedure. It communicates the precision of an estimate as well as its direction and scale. A narrow interval indicates greater precision than a wide interval, although interpretation also depends on the endpoint and the question being asked. No confidence interval for the primary endpoint is reported in the registry record. There is consequently no interval from which to assess either precision or compatibility with different possible effect sizes.

What would a significance test answer?

In general, a significance test evaluates how unusual the observed data would be under a stated null hypothesis and statistical model. A P value does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. The registry record does not report a primary endpoint P value or the test used. No inference about statistical significance can be drawn from the endpoint definition alone.

Why does the imaging population matter?

The stated primary population requires randomization, at least one dose of study medication, and evaluable baseline and exit IVUS imaging, with exit imaging at least 9 months after baseline. This is an endpoint-evaluable definition, not a statement that every randomized participant contributed a primary endpoint. In general, analyses restricted to participants with observed follow-up measurements can be affected if the availability of measurements is related to participant characteristics or outcomes. The record does not report how many participants met the definition, reasons for unavailable imaging, or the method used to handle missing values. It is not possible to assess the direction or size of any resulting bias.

What does the planning illustration represent?

The record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is a stated fraction of the observed effect. Such an illustration is a conditional calculation, not evidence about the trial's actual design justification. It does not mean the trial was planned around those assumptions, and it is not “observed power.” Because the primary result is not reported in the registry record, the observed effect underlying such planning cannot be interpreted from the available information. No calculated planning values are reported in the registry record for this explanation.

What analysis choices remain unknown?

The registry record does not report the primary comparison model, adjustment for baseline measurements or other covariates, the treatment-effect summary used, the handling of protocol deviations, or the approach to missing data. It also does not report whether the analysis was conducted according to randomized assignment or a different analysis population. These choices can affect both the estimated contrast and its uncertainty. The endpoint definition and trial design alone do not establish which methods were used.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary imaging endpoint and multiple secondary imaging outcomes involving atheroma, vessel, and lumen measures. It does not report a multiplicity-adjustment procedure, a hierarchy among the secondary outcomes, or a statistical analysis plan specifying how multiple comparisons were to be interpreted. When many outcomes are examined, the chance of finding at least one apparently unusual result can increase. In general, multiplicity procedures can control that risk, but the record does not say whether any such procedure was used. No outcome results are reported for assessment of this issue.

Missing imaging is especially relevant because the primary endpoint is defined for an IVUS-evaluable population. Participants had to receive at least one dose and have evaluable baseline and exit imaging, with exit imaging at least 9 months after baseline. The number excluded from this endpoint population, reasons for missing or unevaluable scans, and any imputation or sensitivity analyses are not reported in the registry record. Without those details, the completeness of follow-up and the sensitivity of the endpoint analysis to missing data cannot be evaluated.

The record also does not report an intention-to-treat analysis population or explain how participants who discontinued treatment were handled. These are not interchangeable details: population definitions determine which participants contribute to a particular estimate, while missing-data methods determine how unavailable measurements are addressed. The listed primary population definition is informative, but it does not resolve these unreported analysis details.

11. 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: angina pectoris (3.6%), angina unstable (2.4%), chest pain (2.4%), non-cardiac chest pain (1.2%), in-stent arterial restenosis (0.9%).

The registry record lists serious adverse events for Glipizide (GLP) 5 mg and Rosiglitazone (RSG) 4 mg. In each group, the number at risk is 337 and the number affected by serious adverse events is 71. For other adverse events, the number at risk is 337 in the glipizide group, with 117 affected, and 331 in the rosiglitazone group, with 98 affected. These are the counts recorded for the respective categories; they should not be combined or treated as a direct measure of comparative risk without further information.

The most frequently listed serious-event terms include angina pectoris at 3.6%, unstable angina at 2.4%, chest pain at 2.4%, non-cardiac chest pain at 1.2%, in-stent arterial restenosis at 0.9%, and anaemia at 0.9%. These percentages are reported for the terms, but the record does not provide further detail about their group-specific distribution or overlap. Serious-event terms are event categories, and a participant may potentially contribute to more than one category; the record does not clarify the counting convention.

Deaths are recorded as null for both groups. Null should not be read as a reported count of zero; death counts are not reported in the registry record. These safety figures do not, by themselves, establish a causal relationship or support a treatment recommendation.

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

The record documents a Phase III randomized comparison of rosiglitazone and glipizide and specifies an IVUS-based primary endpoint for coronary atherosclerosis. It also defines the endpoint-evaluable population and lists safety-event counts. These details establish the intended comparison and the kinds of measurements recorded, but they do not reveal the primary efficacy result.

In particular, the registry record does not report how PAV changed in either group or the estimated difference between groups. It therefore cannot establish whether the measured plaque burden increased, decreased, or remained similar during follow-up, nor whether the groups differed. It also does not provide a confidence interval or P value for the primary comparison, so neither precision nor statistical significance can be assessed.

The endpoint is an imaging measure, not a direct count of clinical outcomes. A finding about PAV would address the specified change in a coronary-artery segment; it would not automatically answer questions about symptoms, cardiovascular events, survival, or outcomes outside the measured population and follow-up. Those broader conclusions would require relevant outcomes and analyses, which are not reported in the registry record for this explanation.

The safety counts should likewise be read as recorded counts, not as proof that one treatment is safer or more harmful. The registry record does not provide a full account of event timing, duration, severity beyond the serious-event classification, causal attribution, or statistical comparisons. It also records deaths as null rather than reporting a numerical death count. These limitations prevent a complete comparative safety interpretation.

Overall, the posted record supports a description of the trial design, endpoint, analysis-population definition, and selected adverse-event figures. It does not support a conclusion about the primary treatment effect or a clinical recommendation. The absence of results in the registry record is an information limitation, not evidence that the treatments had the same effect.

13. Why This Trial Matters Statistically

This trial raises several important statistical issues because its primary question concerns change in an imaging-derived continuous endpoint, measured in a defined subset of randomized participants. The interpretation depends not only on the endpoint definition, but also on the estimated group contrast, its uncertainty, and how participants without evaluable scans were handled. The registry record supplies the first of these elements but does not report the others.

The distinction between enrollment and endpoint analysis population is consequential. Enrollment is recorded as 672, while the primary endpoint requires dosing and evaluable baseline and exit imaging. The record does not state how many participants contributed to the primary analysis. Thus, enrollment alone cannot indicate how much information supported the endpoint estimate or how representative the evaluable group was of the randomized population.

The record also lists several related imaging outcomes. Examining multiple outcomes can be useful for describing different features of plaque and vessel structure, but it makes prespecification and multiplicity handling important for confirmatory interpretation. The statistical plan and multiplicity approach are not reported, and the primary outcome results are not reported. Accordingly, there is no basis in the record for separating confirmatory findings from exploratory ones.

Finally, an imaging endpoint is distinct from a clinical-event endpoint. Statistical conclusions about change in PAV would be conclusions about that measured surrogate quantity in the defined study population and timeframe; they would not, without additional evidence, establish effects on clinical outcomes. In this case, even the imaging comparison itself is not reported. The record illustrates why transparent reporting of estimates, uncertainty, analysis populations, and missing-data methods is essential to a statistical reading of a trial.

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 central limitation is that the registry record does not report the primary endpoint results. Group-level changes, the between-group contrast, uncertainty estimates, and a statistical test are absent. Without them, the comparative efficacy question cannot be answered from the record, and no numerical interpretation of the primary endpoint is possible.

The endpoint is defined for an IVUS-evaluable population rather than explicitly for all randomized participants. Although the eligibility definition is stated, the analysis population size, the number and characteristics of participants without evaluable imaging, and reasons for missing assessments are not reported in the registry record. Missing-data methods and sensitivity analyses are also not reported. This leaves uncertainty about how the analyzed population may differ from the randomized population.

The statistical analysis plan is not reported. The record does not specify the model for the primary comparison, any covariate adjustment, the method for handling repeated or incomplete measurements, or the multiplicity strategy for the several listed imaging outcomes. It also does not identify the masked parties or describe the randomization procedure. These gaps limit evaluation of the prespecification and robustness of the analysis.

For safety, the registry lists counts and selected serious-event terms but does not report death counts numerically; deaths are recorded as null. Further details needed for a full comparative assessment, including event timing and statistical comparisons, are not reported in the registry record. These limitations are specific to the available record and should not be mistaken for evidence that an analysis or event did not occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Rosiglitazone Versus a Sulfonylurea On Progression Of Atherosclerosis In Patients With Heart Disease And Type 2 Diabetes — NCT00116831.
• Registry record last updated 2017-03-23; status last verified 2017-03.
• Results first posted 2010-03-31.
• 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 III, randomized, triple-masked, parallel-group, active-controlled trial comparing rosiglitazone maleate with glipizide in people with type 2 diabetes mellitus and cardiovascular disease. Enrollment is listed as 672. The official title describes an 18-month multicenter study, with a recorded start date of 2005-01 and primary completion in 2008-08.

The primary endpoint is change from baseline to Month 18 in PAV measured by IVUS in a 40 mm segment of non-intervened coronary arteries. The endpoint population requires at least one dose and evaluable baseline and exit imaging, with exit imaging at least 9 months after baseline. The primary endpoint results, analysis population count, statistical model, missing-data approach, and multiplicity procedure are not reported in the registry record. Safety counts and selected serious-event terms are listed, while death counts are null.