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 Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation (NCT01186250), a randomized phase 2 study. The primary outcome is Insulin Levels Area Under Curve(AUC).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01186250 |
| Phase | Phase 2 |
| Condition | Cardiac Allograft Vasculopathy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 18 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Stanford University |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns human heart transplant recipients. The registry record identifies cardiac allograft vasculopathy as the condition and describes insulin resistance and the development or progression of cardiac allograft vasculopathy as study objectives. Eligibility criteria and further details about the participant population are not reported in the registry record.
Intervention
Participants assigned to the intervention arm received pioglitazone. The record describes it as an insulin-sensitizing agent and lists it as a drug intervention. Dosing, treatment duration, adherence, and other administration details are not reported in the registry record.
Comparator
The comparator was placebo. The trial is listed as randomized, with a parallel model and triple masking. The record does not explain how the masking was implemented or identify which roles were masked.
Primary question
The posted primary endpoint asks how insulin levels during an oral glucose tolerance test changed from baseline to one year. The outcome is the area under the curve for insulin levels, measured in h*pmol/L. The registry record also states an objective concerning cardiac allograft vasculopathy, but the posted primary result is the insulin measure. The posted result therefore describes insulin change by arm; it does not provide a direct estimate of the treatment contrast or establish an effect on cardiac allograft vasculopathy.
3. Trial Design
The registry record describes a randomized, triple-masked, parallel-group phase 2 trial comparing pioglitazone with placebo in heart transplant recipients. Stanford University is listed as the sponsor. The study status is completed, with enrollment of 18 participants. The recorded start was 2010-07 and primary completion was 2013-08.
The two arms each have a posted primary-outcome sample size of 9. The parallel design means participants were assigned to one of the two groups rather than receiving both interventions in sequence, as reflected in the registry's model designation. Random allocation and triple masking are recorded, but the method used to generate or conceal allocation and the specific parties masked are not reported in the registry record. Details of the treatment schedule, follow-up procedures, adherence, and handling of treatment changes are also not reported in the registry record.
The study description identifies two broad aims: assessing insulin resistance and examining whether pioglitazone therapy after transplantation affects the development or progression of cardiac allograft vasculopathy. The listed primary endpoint is change in insulin levels during an oral glucose tolerance test at one year. The record lists secondary outcomes concerning intimal volume, fasting glucose, the TG/HDL ratio, maximal intimal thickness measured by intravascular ultrasound, ADMA, and high-sensitivity C-reactive protein. These listed outcomes indicate the range of measurements in the registry, but they do not establish that every outcome was collected for every participant or analyzed.
The registry record does not report the trial's own sample-size justification, a detailed statistical analysis plan, the randomization procedure, or an interim-analysis plan. Those omissions limit how fully the design and intended analysis can be reconstructed from the posted record.
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
| Stage | Pioglitazone | Placebo |
|---|---|---|
| STARTED | 9 | 9 |
| COMPLETED | 8 | 9 |
| NOT COMPLETED | 1 | 0 |
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: Double-blind randomized clinical trial of pioglitazone versus placebo from 2010 to 2013 in heart transplant recipients who were 1-4 years post-transplant.Eighteen heart transplant patients aged 22 to 72 years were randomized (9 to pioglitazone, 9 to placebo)
| Characteristic | Unit | Pioglitazone | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 9 | 9 | 18 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 | 8 | 16 |
| Age, Categorical: >=65 years | Participants | 1 | 1 | 2 |
| Age, Continuous | years | 50.8 (23 to 72) | 49.2 (22 to 72) | 50.0 (22 to 72) |
| Sex: Female, Male: Female | Participants | 0 | 1 | 1 |
| Sex: Female, Male: Male | Participants | 9 | 8 | 17 |
| Region of Enrollment: United States | participants | 9 | 9 | 18 |
6. Primary Endpoint
The registry lists the primary outcome as Insulin Levels Area Under Curve(AUC), measured over Baseline and 1 year.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | h*pmol/L |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the change from baseline in insulin levels during an oral glucose tolerance test at one year. The measure is the area under the curve (AUC), with units of h*pmol/L. An AUC summarizes insulin measurements across the test period rather than describing only a single measurement. In general, this can represent the overall insulin response during the test; the specific sampling schedule and calculation details are not reported in the registry record.
The study description links the endpoint to its objective of assessing insulin resistance in heart transplant recipients. In general, insulin responses during an oral glucose tolerance test can be used to characterize glucose-insulin physiology. The endpoint is therefore relevant to the stated metabolic objective, but it is not itself a direct measurement of cardiac allograft vasculopathy. The registry lists outcomes involving intimal volume and maximal intimal thickness, among others, as secondary outcomes.
The posted results give an arm-specific mean change and a 95% confidence interval for each group. The pioglitazone arm's mean change is -47.7 h*pmol/L, with a 95% confidence interval from -171.3 to 75.9. The placebo arm's mean change is 10.7 h*pmol/L, with a 95% confidence interval from -76.8 to 98.2. These are changes within each arm. The registry record does not post a treatment-versus-placebo estimate for this endpoint, so the arm-specific results should not be mistaken for a direct comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary result reports mean change in insulin AUC from baseline to one year. In the pioglitazone arm, the mean change is -47.7 h*pmol/L, and the 95% confidence interval ranges from -171.3 to 75.9. In the placebo arm, the mean change is 10.7 h*pmol/L, and the 95% confidence interval ranges from -76.8 to 98.2. The point estimates describe the average change within each arm; the intervals communicate substantial uncertainty around those estimates.
Both confidence intervals include zero. In general, that means the posted intervals are compatible with no average change in the corresponding arm, as well as with changes in either direction within their bounds. This is not a test of whether the treatment arms differ. A confidence interval for each arm's change and a confidence interval for the between-arm contrast answer different questions. The registry record does not post a direct treatment-effect estimate, its confidence interval, or a p-value for the primary endpoint. A treatment difference should not be inferred by comparing the arm-specific interval limits or by subtracting the two means.
The sample is small: the record lists 18 enrolled participants and a primary-result sample size of 9 in each arm. With limited numbers, estimates can be imprecise, and a few individual observations may have considerable influence on an average. The posted confidence intervals are wide relative to the point estimates, illustrating that uncertainty. The record does not describe the distribution of individual changes, so it is not possible to assess from these summaries whether unusual values or distributional features affected the means.
The endpoint concerns insulin response, not a direct clinical event or a direct measurement of cardiac allograft vasculopathy. Although the study description includes an objective about vasculopathy, the primary result alone cannot answer that objective. The record lists several secondary measures that may be relevant to metabolic status or vascular changes, but does not post their results in the registry record in the registry entry. Their findings, and any relationship among them, are therefore not available for interpretation from this record.
The registry lists zero serious adverse events and zero other adverse events in each arm, with 9 participants at risk in each group. These are the posted counts, not proof that no unrecorded or unreported events occurred. Death counts are not reported. Overall, the posted primary data are descriptive arm-level estimates with considerable uncertainty; they do not, on their own, establish a comparative treatment effect or resolve the study's broader objectives.
9. Statistical Methods Explained
The registry identifies the primary endpoint as a continuous measure and specifies the mean as its summary parameter. A continuous endpoint can take values across a scale rather than belonging to a small set of categories. The mean describes the arithmetic average for the observations included in a group. Here, the result is expressed as change in insulin AUC from baseline to one year, in h*pmol/L. The record does not give individual observations or further details about the endpoint calculation.
What do the confidence intervals express?
The posted uncertainty measure is a 95% confidence interval. In general, a confidence interval describes the uncertainty associated with an estimated quantity under the statistical method used. It is not a range containing a known proportion of individual participant results, and it does not mean that every value inside the interval is equally plausible. Its width depends on features such as the amount of information in the data and variability in the outcome. The registry does not describe the formula or assumptions used to construct these intervals.
For the pioglitazone arm, the mean change is -47.7 h*pmol/L and its interval is -171.3 to 75.9. For the placebo arm, the mean change is 10.7 h*pmol/L and its interval is -76.8 to 98.2. Both intervals span zero. In general, zero represents no change when the target quantity is a change from baseline. The intervals thus do not pin down the direction of average change with precision. This statement concerns each arm's change separately, not the difference between arms.
Why is a direct comparison important?
A randomized comparison is designed to assess how outcomes differ between groups assigned to different treatments. The relevant treatment-effect estimate would directly contrast the pioglitazone arm with the placebo arm, with uncertainty quantified for that contrast. Separate estimates of change within each group are not a substitute: participants in both groups can change over time for reasons unrelated to the assigned intervention. The registry record posts arm-specific means and intervals but no direct comparative estimate or p-value for the primary endpoint. A comparison cannot be reconstructed without calculating a new statistic, which is not appropriate from these posted summaries.
The registry lists 9 participants for the primary result in each arm. That number indicates the size of the group attached to each posted result, but the record does not explain whether all enrolled participants contributed to the endpoint or how missing measurements were handled. Small group sizes generally lead to limited information and potentially imprecise estimates. The intervals are consistent with this uncertainty, but no additional measure of precision should be inferred from the sample size alone.
What do planning calculations mean?
In general, sample-size planning uses assumptions about the effect to detect, the variability of the outcome, the significance level, and the desired power. The registry's planning note describes an illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the illustrated effect is a stated fraction of the observed effect. Such illustrations are not the original trial design and do not represent observed power. The registry record does not report the trial's own sample-size justification. No planning sample-size results are included in the registry record for this analysis.
The record also does not report the statistical model used for the primary endpoint, covariate adjustment, or any transformation of the outcome. In general, modeling choices can affect estimates and their uncertainty, especially when data are limited or assumptions about the outcome distribution are not well matched to the observations. The mean and confidence intervals alone do not reveal which modeling choices were made.
Randomization can support a fair comparison by reducing systematic differences between groups at assignment, on average. Masking can reduce certain forms of bias in care or outcome assessment. Those are general design principles, not confirmation of how well these features were implemented in this study. The registry records randomization and triple masking but does not report operational details, allocation concealment, or checks of baseline comparability.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures, including the primary endpoint and 6 secondary outcomes. The secondary outcomes cover intimal volume, fasting glucose, the TG/HDL ratio, maximal intimal thickness by intravascular ultrasound, ADMA, and high-sensitivity C-reactive protein. The record reports no analyses. Results for the secondary outcomes are not reported in the registry record, so their estimated effects and uncertainty cannot be assessed.
In general, evaluating multiple outcomes raises a multiplicity issue: the more statistical questions examined, the greater the chance that at least one result may appear notable by chance if each is assessed separately. Prespecified priorities and adjustment strategies can help readers interpret a set of tests. The registry record does not report whether multiplicity was addressed, which outcomes were included in any formal testing strategy, or whether analyses were prespecified. No conclusion about adjustment or selective reporting can be drawn from the available information.
Missing-data methods and analysis populations are also not reported in the registry record. The primary result lists 9 participants in each arm, but the record does not explain whether these are all randomized participants, all participants with observed endpoint measurements, or another analysis set. It does not state how missing baseline or one-year measurements were handled, whether any imputation was used, or whether participants were analyzed according to original assignment.
In general, missingness can affect interpretation when participants without an observed result differ from those with one. Without information about the amount, reasons, and handling of missing data, readers cannot assess the direction or size of any resulting bias. The posted arm counts are useful context, but they do not resolve these questions.
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 |
|---|---|---|---|
| Pioglitazone | 0 | 9 | 0.0% |
| Placebo | 0 | 9 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pioglitazone | 0 of 9 |
| Placebo | 0 of 9 |
The registry lists 9 participants at risk for serious adverse events in each arm. The number affected by a serious adverse event is recorded as 0 in the pioglitazone arm and 0 in the placebo arm. For other adverse events, the record also lists 9 participants at risk in each arm and 0 affected in each arm. These are the counts posted for the registry outcome.
These counts should be read as the adverse-event figures recorded in the registry, not as evidence that the treatments have no safety risks. With a small number of participants, uncommon events may not occur during observation even if they are possible. The record does not provide event descriptions, collection procedures, observation time by participant, or an explanation of how events were attributed. Death counts are not reported.
In general, adverse-event counts describe what was recorded in a study population over its observation period. They do not by themselves establish comparative safety, particularly when the study is small and the registry record does not provide detailed event definitions or exposure information. The posted figures therefore support only the narrow statement that no serious or other adverse events are listed as affecting participants in either arm.
12. What the Result Does, and Does Not, Mean
The primary result provides a descriptive estimate of average change in insulin AUC within each randomized arm. The mean change is -47.7 h*pmol/L for pioglitazone and 10.7 h*pmol/L for placebo, with 95% confidence intervals of -171.3 to 75.9 and -76.8 to 98.2, respectively. Both intervals include zero, and both span values on either side of zero. The result is therefore uncertain about the direction and size of average change within each group.
These estimates do not provide a direct treatment-versus-placebo contrast. The registry record does not post a between-arm effect estimate, its uncertainty, or a p-value for the primary endpoint. Consequently, the arm-specific results cannot establish whether the groups differed in their change. A difference should not be calculated or inferred from the separate means and intervals.
The endpoint is insulin response during an oral glucose tolerance test. It does not directly measure cardiac allograft vasculopathy or a clinical event. The study description states that the trial also sought to assess the development or progression of cardiac allograft vasculopathy, and the registry lists secondary outcomes such as intimal volume and maximal intimal thickness. Their results are not reported in the registry record. The primary result therefore cannot answer the broader vasculopathy question.
The registry reports an enrollment of 18, with 9 participants listed for the primary result in each arm. Limited group sizes and wide intervals mean that the estimates are not precise. They do not establish that a meaningful effect is absent, nor do they establish that a meaningful effect is present. The results should be understood as uncertain estimates from a small trial rather than as a definitive answer to either study objective.
The adverse-event record lists zero serious and zero other adverse events in both groups, but those counts do not rule out uncommon events or provide a comprehensive comparative safety assessment. The record also does not report missing-data methods, analysis populations, or detailed statistical methods. These gaps further constrain interpretation of the posted results.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it distinguishes an outcome's relevance from the strength of evidence available to answer a question. The study description concerns insulin resistance and cardiac allograft vasculopathy, while the posted primary endpoint is change in insulin AUC. The endpoint is connected to the metabolic objective, but it is not itself a direct measure of vasculopathy. Keeping the outcome and the scientific question aligned is essential when interpreting any result.
The record also illustrates the distinction between within-arm change and a randomized treatment comparison. Separate arm means describe what was observed in each group relative to baseline. The causal comparison of interest is the difference between outcomes under the randomized assignments, estimated directly with its uncertainty. Because the registry posts no such estimate for the primary endpoint, the available arm summaries do not answer that comparative question.
Precision matters as much as the point estimate. The confidence intervals are broad and include zero for both arms, so the direction of average change is not tightly determined. A result that is uncertain is not equivalent to evidence of no effect. Conversely, a point estimate alone does not demonstrate an effect, particularly without a direct comparison and its uncertainty.
The record lists multiple secondary outcomes, but does not report their results or a multiplicity strategy. This highlights why outcome hierarchy and transparent analysis reporting matter: without those details, readers cannot determine how a collection of findings should be interpreted together. Similarly, the absence of information about missing data and analysis populations prevents a complete assessment of who contributed to the results.
Finally, planning illustrations based on an observed effect are conceptually different from the trial's original design justification and from observed power. The registry explicitly characterizes its planning note as an illustration, while the trial's own sample-size justification is not reported. Separating design assumptions, observed estimates, and uncertainty helps prevent overstatement.
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 gives a limited account of the trial methods. It identifies randomization, triple masking, and a parallel design, but does not report the randomization procedure, allocation concealment, or which people were masked. It also does not describe eligibility criteria in detail, intervention dosing, treatment duration, adherence, or follow-up procedures. These omissions restrict assessment of how the stated design was implemented.
The primary result is posted as arm-specific means and confidence intervals rather than as a direct treatment contrast. The registry record does not provide a comparative estimate, p-value, or detailed statistical model. Without individual-level data or an explicitly reported contrast, the treatment effect cannot be evaluated from the posted summary alone.
The reported sample is small, with 18 enrolled and 9 participants listed in each arm for the primary result. The record does not explain whether those counts represent all randomized participants or only participants with available endpoint measurements. Missing-data handling and analysis populations are not reported. It is therefore not possible to determine from the record whether missing observations or exclusions influenced the estimates.
The trial description includes a cardiac allograft vasculopathy objective, but the posted primary outcome measures insulin AUC. Although the registry lists several secondary outcomes relevant to metabolic or vascular measures, their results are not reported in the registry record. The record also does not report a multiplicity plan, a detailed endpoint measurement protocol, or the trial's own sample-size justification. These specific gaps limit conclusions about both the primary comparison and the broader study objectives.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Clinical Trial of Pioglitazone for Prevention of Cardiac Allograft Vasculopathy After Heart Transplantation — NCT01186250.
- Registry record last updated 2016-08-18; status last verified 2016-07.
- Results first posted 2016-08-18.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed, randomized, triple-masked, parallel-group phase 2 trial sponsored by Stanford University. It enrolled 18 participants and compared pioglitazone with placebo, with 9 participants listed per arm for the primary result. The study's stated aims concerned insulin resistance and cardiac allograft vasculopathy after heart transplantation.
The posted primary endpoint is change from baseline to one year in insulin levels during an oral glucose tolerance test, summarized as mean AUC in h*pmol/L. The pioglitazone mean change is -47.7, with a 95% confidence interval from -171.3 to 75.9; the placebo mean change is 10.7, with a 95% confidence interval from -76.8 to 98.2. A direct comparative estimate is not reported in the registry record.
The record lists 6 secondary outcomes but reports no analyses. It records zero serious and zero other adverse events in each arm; death counts are not reported. Details of missing-data handling, analysis populations, multiplicity, and the trial's own sample-size justification are not reported in the registry record.