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 Pioglitazone Treatment for Hyperglycemic Acute Ischemic Stroke (NCT04123067), a randomized phase 1, phase 2 study. The primary outcome is Neurological Status.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04123067 |
| Phase | Phase 1, Phase 2 |
| Condition | Stroke, Acute, Hyperglycemia, Diabetes |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Milton S. Hershey Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with acute ischemic stroke and hyperglycemia, with diabetes also listed among the conditions. The registry rationale focuses on high-risk diabetic stroke patients and the possibility of improving neurological recovery and reducing morbidity and mortality. The record does not provide further eligibility details, such as specific glucose thresholds, stroke criteria, or restrictions on participant characteristics; these are not reported in the registry record.
Intervention
The pioglitazone treatment group was assigned oral pioglitazone 45 mg daily for three subsequent days, with treatment initiated within 12h of stroke symptom onset. The study objective was to examine whether pioglitazone could improve clinical outcomes in this setting. The record does not report whether the subject assigned to this group received the planned treatment.
Comparator
The comparison was an oral placebo tablet administered daily for three subsequent days, also initiated within 12h of stroke symptom onset. The registry describes randomized allocation, quadruple masking, and a parallel-group model. The allocation ratio and details about who was masked are not reported in the registry record.
Primary question
The primary outcome was neurological status at 90 days post stroke, assessed with the NIH-Stroke scale, which ranges from 0 to 42, with 0 indicating no deficits and 42 the worst score. The intended clinical question was whether outcomes differed between the pioglitazone and placebo groups. However, the record says the subject who received placebo was lost to follow up and 90-day outcome data were not collected. It does not give a comparison estimate or analysis result, so the treatment question cannot be answered from the posted outcome information.
3. Trial Design
The registry describes a randomized, quadruple-masked, parallel-group study comparing pioglitazone with placebo. It is listed as Phase 1 and Phase 2. The sponsor is Milton S. Hershey Medical Center. The recorded enrollment is 1, and the study status is terminated. The listed start date is 2020-09-01, with primary completion on 2021-04-07. The reason for termination is not reported in the registry record.
The pioglitazone group was assigned oral pioglitazone 45 mg daily for three subsequent days, initiated within 12h of stroke symptom onset. The placebo group was assigned an oral placebo tablet daily for three subsequent days, with the same stated initiation window. The registry does not report the allocation ratio, the randomization method, or whether treatment adherence was assessed. It also does not specify which parties were masked under the quadruple-masking designation.
The primary outcome was neurological status at 90 days post stroke, measured with the NIH-Stroke scale. The record lists two secondary outcome topics: concentrations of markers of neutrophil activation and function, and concentrations of stress response markers including cortisol, norepinephrine and epinephrine. Four outcome measures are listed in total, but the record does not describe all four in the available outcome information.
The primary outcome description states that the subject who received placebo was lost to follow up and that 90-day outcome data were not collected. There are no analysis entries. The registry does not report a statistical analysis plan, a sample-size justification, interim analyses, or the reason the study was terminated. The posted design therefore describes the intended comparison, but it does not provide an analyzed comparison of neurological outcomes.
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 Treatment Group | Placebo Group |
|---|---|---|
| STARTED | 0 | 1 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Pioglitazone Treatment Group | Placebo Group |
|---|---|---|
| Lost to Follow-up | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Subject that received Placebo was lost to follow up and 90 day outcome data was not collected.
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: Pioglitazone Group contains 0 participants because the Responsible Party terminated the study following the enrollment of first study subject
| Characteristic | Unit | Pioglitazone Treatment Group | Placebo Group | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 1 | 1 | |
| Age, Continuous | years | — | 72 (SD 0) | 72 (SD 0) |
| Sex: Female, Male: Female | Participants | — | 1 | 1 |
| Sex: Female, Male: Male | Participants | — | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | — | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | — | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | — | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | — | 0 | 0 |
| Race (NIH/OMB): White | Participants | — | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | — | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | — | 1 | 1 |
| Region of Enrollment: United States | participants | — | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Neurological Status, measured over 90 days post stroke.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is neurological status at 90 days post stroke. It is measured using the NIH-Stroke scale, a score from 0 to 42 in which 0 means no deficits and 42 means the worst score. The scale gives a standardized way to describe neurological function at the stated follow-up time. In general, a clinical outcome measure can make treatment groups comparable on an outcome relevant to the study objective, provided the measurements are collected and analyzed appropriately.
The registry’s objective was to determine whether pioglitazone could improve clinical outcomes in hyperglycemic acute ischemic stroke. Neurological status is relevant to that objective because the study rationale concerns neurological recovery. The record does not define a particular clinically meaningful difference on the scale, explain how scores would be summarized, or specify whether the primary comparison would use a mean, a distributional measure, or categories. Those details are not reported in the registry record.
Most importantly, the primary outcome description says the subject who received placebo was lost to follow up and 90-day outcome data were not collected. As a result, the record does not provide an observed 90-day score for that subject or a reported treatment comparison. The endpoint’s definition alone cannot establish whether outcomes differed between the groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry states a clear treatment question: whether pioglitazone can improve clinical outcomes in people with hyperglycemic acute ischemic stroke. The comparison was designed around oral pioglitazone and an oral placebo, with both regimens intended to begin within 12h of stroke symptom onset and continue daily for three subsequent days. The listed primary endpoint was neurological status at 90 days post stroke.
There is no posted primary-outcome estimate to interpret. The registry says the subject who received placebo was lost to follow up and that 90-day outcome data were not collected. It does not report a group contrast, confidence interval, test statistic, p-value, or analysis result for neurological status. There are no analysis entries in the registry record. Accordingly, the posted information does not quantify the direction, size, or precision of a treatment effect.
In general, an estimate describes the observed contrast between groups, while a confidence interval describes the range of values compatible with the data and the analysis assumptions. Without a reported endpoint estimate and its uncertainty, neither the magnitude nor the precision of a possible difference can be assessed. The absence of a reported estimate is not evidence that the groups had the same outcome; it means the record does not furnish a result that can establish the comparison.
The enrollment is recorded as 1. That makes the scale of the recorded enrollment important context, but it does not identify how treatment was allocated, whether the planned intervention was received, or what the unobserved outcome would have been. The missing placebo follow-up further prevents a complete interpretation of the stated primary endpoint. The record does not report an imputation method or another approach for handling the missing outcome.
The registry lists secondary outcomes concerning neutrophil activation and function, and stress response markers including cortisol, norepinephrine and epinephrine. It lists four outcome measures overall, but does not provide analyzable results for those outcomes in the information. The trial status is terminated, and the reason is not reported in the registry record. These registry entries describe the scope and completeness of the record; they do not explain why enrollment was limited or why the study ended.
The planning assumptions refer to a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are assumptions for planning illustrations, not evidence that a particular test or design calculation was used in the trial. No sponsor analysis is reported for the primary outcome, so there is no sponsor estimate to compare with a recalculation.
Overall, the posted information documents a planned randomized comparison and the primary endpoint definition, but does not provide the primary outcome data needed to assess the clinical question. It should be read as an incomplete outcome record rather than as evidence for or against a difference between pioglitazone and placebo.
9. Statistical Methods Explained
Randomized allocation is intended, in general, to make assigned treatment groups comparable with respect to measured and unmeasured characteristics at the start of a study. It does not guarantee balance in a particular trial, especially when the recorded enrollment is small. The registry identifies the study as randomized but does not report the allocation sequence method, concealment procedures, or allocation ratio. Therefore, the record does not support a detailed assessment of how randomization was implemented.
What does masking mean?
The study is listed as quadruple-masked. Masking is used in general to reduce the chance that knowledge of assigned treatment affects care, outcome assessment, or reporting. The registry does not identify the four parties covered by this label or describe how masking was maintained. The presence of a masking designation is a design feature; by itself it does not show whether masking was successful.
How should the endpoint scale be understood?
The NIH-Stroke scale is described as ranging from 0 to 42, with 0 indicating no deficits and 42 the worst score. Scores on a bounded clinical scale may be summarized in more than one way. A mean-based comparison focuses on average score differences; a distributional analysis can instead examine how scores are spread across possible values. The registry does not state which summary or model was planned. It also does not define a threshold for a clinically important difference.
In general, the choice of analysis should reflect the outcome’s scale, the study design, and the question of interest. If a statistical model assumes a particular distribution or a particular relationship between the outcome and treatment, its assumptions should be checked where the data permit. Over-dispersion, for example, means that observed variability exceeds what a model assumes; if present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. The registry does not report an analysis model or diagnostic checks, and the available outcome description does not permit evaluation of these issues.
What does a confidence interval communicate?
As a general statistical concept, a confidence interval expresses uncertainty around an estimated quantity under the method’s assumptions. A narrow interval indicates greater precision than a wide interval, while an interval that includes values consistent with different conclusions may leave the comparison uncertain. An interval is not a guarantee that the true value lies within its endpoints. The registry record does not report a confidence interval for the primary outcome.
What does a p-value communicate?
In general, a p-value describes how surprising data at least as incompatible with a specified null model would be, assuming that model and the analysis assumptions. It is not the probability that a treatment works, nor does it describe the size or clinical importance of an effect. A p-value is most useful alongside an effect estimate, uncertainty interval, prespecified analysis, and information about missing data. No primary-outcome p-value is reported in the registry record.
How do planning illustrations differ from trial results?
The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect defined as a fraction of the observed effect. These assumptions describe planning illustrations. They do not establish the study’s original sample-size justification, which is not reported in the registry record. A planning calculation is not an observed result and is not observed power. It cannot replace an analysis of collected outcomes, and it does not show that a study had adequate precision.
The planning description also distinguishes participants per arm for non-time-to-event outcomes from a total number of events for time-to-event calculations. The primary outcome is neurological status at a stated follow-up, rather than a time-to-event result as described in the record. The assumptions alone do not supply an observed effect or a usable treatment comparison.
What can be concluded from the posted analysis information?
The registry lists no analysis entries, and the primary outcome description reports that 90-day data were not collected for the subject who received placebo. There is therefore no reported model, estimate, uncertainty interval, or significance test to interpret. The registry does not describe interim analyses, adjustment for multiplicity, or an analysis population. These omissions mean the statistical methods actually used, if any, are not reported in the registry record. General statistical principles can explain how such methods would be interpreted, but they cannot fill in the missing study-specific analysis information.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures overall. It names secondary outcome topics concerning neutrophil activation and function, and stress response markers including cortisol, norepinephrine and epinephrine. The primary outcome is neurological status at 90 days post stroke. The record indicates that the primary outcome has several categories or time points and is not reduced to one comparison. It does not provide a single treatment-effect estimate for that outcome.
Multiplicity arises in general when several outcomes, time points, or comparisons are examined. Considering many results can increase the chance that at least one appears notable by chance. Statistical approaches can address this, but the appropriate approach depends on the prespecified questions and analysis plan. The registry does not report a multiplicity adjustment, a testing hierarchy, or which outcome comparison was designated as the sole confirmatory test. These details are not reported in the registry record.
The primary outcome description states that the subject who received placebo was lost to follow up and that 90-day outcome data were not collected. The record does not state why follow-up was missed, whether other measurements were available, or how missing outcomes were handled. It does not report imputation, sensitivity analyses, or assumptions about the missingness mechanism. Missing outcome data can make a treatment comparison less precise and can bias it if the missingness is related to the outcome or treatment in a way not addressed by the analysis. That is a general concern, not a claim about the cause of this missing observation.
The registry does not identify an intention-to-treat, per-protocol, or other analysis population. It also does not report an analysis plan or analysis entries. Therefore, the handling of randomized assignment, treatment receipt, and missing outcome information cannot be assessed from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo Group | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pioglitazone Treatment Group | 0 of 0 |
| Placebo Group | 0 of 1 |
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 Treatment Group | 0 of 0 |
| Placebo Group | 0 of 1 |
The registry’s serious adverse event entries list 0 at risk and 0 affected for the pioglitazone treatment group. For the placebo group, the entries list 1 at risk and 0 affected. Deaths are listed as 0 in both groups. The other adverse event entries list 0 at risk and 0 affected for the pioglitazone group, and 1 at risk and 0 affected for the placebo group. No top serious adverse event terms are listed.
These figures should be read as the registry’s recorded adverse-event counts, not as evidence that the treatments have comparable safety. The at-risk entries differ between the groups, and the pioglitazone group has 0 recorded at risk in these entries. The record does not explain the basis for those denominators or report additional exposure details. With such limited recorded information, an absence of affected entries cannot establish that no adverse events occurred outside what was recorded, or characterize event risk reliably.
The registry does not provide definitions or further detail about collection and follow-up for these adverse event entries. The counts do not resolve the primary neurological outcome question, and they should not be used to infer a treatment effect. The reason for termination is also not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes the intended comparison and the primary outcome definition. It describes randomization, quadruple masking, a parallel-group design, pioglitazone 45 mg, and an oral placebo. Both regimens were intended to be given daily for three subsequent days, beginning within 12h of stroke symptom onset. The stated primary endpoint was neurological status at 90 days post stroke, assessed with the NIH-Stroke scale.
The record does not establish whether pioglitazone improved, worsened, or had no effect on neurological status. The subject who received placebo was lost to follow up, and the 90-day outcome data were not collected. No analysis entries or primary outcome comparison are reported. Without an outcome estimate and its uncertainty, the direction, magnitude, and precision of a possible difference cannot be described.
This is not the same as finding no difference. A result showing little evidence of a difference would require an analyzed comparison, with enough information to assess uncertainty. In general, an estimate and confidence interval help distinguish a precise result from an inconclusive one. Neither is reported for the primary outcome in the registry record.
The recorded enrollment is 1, and the study is marked terminated. Those details do not explain why the study ended, whether treatment was received as planned, or how the available record relates to the study’s original objectives. The termination reason, adherence information, and original sample-size justification are not reported in the registry record. No inference about the reason for termination is warranted from the status alone.
The adverse-event entries report zero affected for the listed groups, but the at-risk entries are 0 for pioglitazone and 1 for placebo. These counts are too limited to support broad conclusions about comparative safety. Likewise, the listed secondary outcome topics do not constitute results; the registry record does not provide outcome analyses for them.
In short, the record describes a clinical question and a planned study design, but does not report data adequate to answer that question. It should not be interpreted as proof of benefit, proof of no benefit, or a comparative safety conclusion.
13. Why This Trial Matters Statistically
This trial is statistically important as an example of the difference between a registered design and an interpretable outcome analysis. The registry specifies a randomized comparison and a clinical endpoint, but the endpoint data needed for the comparison are not reported. A protocol question can be well defined while the posted evidence remains insufficient to estimate an effect.
Follow-up completeness matters because a treatment comparison depends on observing outcomes in the groups being compared. Here, the registry explicitly states that 90-day outcome data were not collected for the subject who received placebo. Without those data and a reported method for handling their absence, the primary outcome cannot be assessed as a group contrast. Statistical methods cannot recover an unobserved outcome without assumptions, and the registry does not report any such method.
The enrollment of 1 also highlights why the scale and completeness of the data matter to precision. Randomization and masking are useful design features in general, but they do not create information where outcome measurements are unavailable. Nor does a planning calculation substitute for observed outcomes. The planning assumptions listed in the record are not a report of the trial’s original design justification or evidence of the achieved precision.
The record also illustrates why safety counts require denominators and context. The adverse-event entries show different at-risk counts by group, and the recorded affected counts are zero. Those figures alone cannot establish comparative safety, particularly without further information about exposure and event collection.
For biostatisticians and clinical researchers, the central lesson is to separate the intended estimand and design from the actual posted analysis. The study objective, treatment schedules, endpoint, and status are documented; the comparative estimates, uncertainty, analysis population, and missing-data approach are not. That distinction preserves what the record can establish while avoiding conclusions it cannot support.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation is the absence of collected 90-day outcome data for the subject described as receiving placebo. Because the registry provides no primary-outcome comparison or analysis, the endpoint cannot be interpreted as an estimate of the relative outcomes under pioglitazone and placebo. The record does not state how the missing follow-up was handled.
The enrollment is recorded as 1, and the study is listed as terminated. The registry does not explain the termination, give a reason for the recorded enrollment, or report whether participants received their assigned regimens. It also does not provide the allocation ratio or detailed eligibility criteria. These gaps limit interpretation of recruitment, treatment implementation, and the study population.
The primary outcome is defined by the NIH-Stroke scale and a 90-day time point, but the record does not specify the planned summary measure, model, clinically meaningful threshold, or statistical analysis plan. It notes that the outcome has several categories or time points and is not reduced to one comparison. The registry does not report how those dimensions were to be handled.
Four outcome measures are listed, while only two secondary outcome topics are named in the record. No outcome analyses are listed. The registry does not describe multiplicity control, interim analyses, analysis populations, or missing-data sensitivity analyses. The original sample-size justification is not reported in the registry record.
Safety information is also limited: the listed at-risk counts differ between groups, and no further detail about event collection or exposure is provided. These limitations are specific to the information recorded and should not be interpreted as explanations for study conduct or results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pioglitazone Treatment for Hyperglycemic Acute Ischemic Stroke — NCT04123067.
- Registry record last updated 2022-09-15; status last verified 2022-08.
- Results first posted 2022-09-15.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry describes a Phase 1 and Phase 2, randomized, quadruple-masked, parallel-group study sponsored by Milton S. Hershey Medical Center. It compares oral pioglitazone 45 mg daily for three subsequent days with oral placebo on the same schedule, with treatment initiated within 12h of stroke symptom onset. The stated primary outcome is NIH-Stroke scale neurological status at 90 days post stroke.
The recorded enrollment is 1, and the study status is terminated. The registry says the subject who received placebo was lost to follow up and 90-day outcome data were not collected. No analysis entries are listed, and no primary outcome comparison is reported. Secondary outcome topics include neutrophil activation and function markers and stress response markers including cortisol, norepinephrine and epinephrine. The record does not report the termination reason, original sample-size justification, or statistical analysis plan.