Effect of Pentoxifylline on Proteinuria in Korean Type 2 Diabetic Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Pentoxifylline on Proteinuria in Korean Type 2 Diabetic Patients (NCT01382303), a randomized phase 4 study. The primary outcome is Percentage Change in Proteinuia.

2. Clinical Question

The study is identified as phase 4 and completed. Its stated purpose was to evaluate the effects of pentoxifylline on proteinuria in Korean patients with type 2 diabetes. The registry also lists albuminuria, eGFR, creatinine, fasting glucose, and TNF-a among secondary outcomes. These outcomes can add context about the pattern of measurements, but they do not replace the prespecified primary question. The record does not report a detailed protocol or explain how the investigators intended to interpret multiple outcomes together.

3. Trial Design

The registry describes a prospective, randomized, double-blind, multicenter study with a parallel-group model. Its official title calls the comparison active control, but the listed interventions and arm descriptions name pentoxifylline and a placebo tablet. The registry identifies Ajou University School of Medicine as the sponsor. The study is marked completed, and the record gives a start date of 2010-10-25 and a primary completion date of 2013-12-20.

The intended enrollment was 174. The posted primary outcome summaries include 52.0 participants in the pentoxifylline arm and 70.0 in the placebo arm. The secondary continuous outcome summaries use the same arm-specific counts. These outcome counts do not explain how enrollment relates to the participants analyzed; reasons for differences in the numbers are not reported in the registry record. They should not be treated as proof of the analysis population or of the handling of missing observations.

The primary outcome is described as percentage change in proteinuria, measured as change in urine protein-to-creatinine ratio from baseline to 24 weeks. The reported group summaries are -23.0 for pentoxifylline and -4.0 for placebo, with inter-quartile ranges reported as -50.0 to 10.0 and -30.0 to 40.0, respectively. The registry labels the summary parameter as a mean while specifying inter-quartile range as its dispersion measure. It does not clarify this combination or provide an explicit between-group analysis for the primary endpoint.

The record lists six outcome measures, but the secondary results included in the registry concern five named outcomes. Numerical summaries are posted for three of those outcomes. There are no reported analyses in the registry record. Details such as allocation concealment, the precise blinding procedures, protocol deviations, and any interim analyses are not reported in the registry 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

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 Percentage Change in Proteinuia, measured over baseline and 24 weeks.

The primary endpoint measures percentage change from baseline to 24 weeks in the urine protein-to-creatinine ratio. This ratio combines a urine protein measurement with a urine creatinine measurement and is used to characterize proteinuria while accounting for variation in urine concentration. A change from baseline expresses how the measurement moved over the study period, rather than describing only a value at one visit.

The registry gives the pentoxifylline arm’s summary as -23.0 and the placebo arm’s as -4.0, in the stated unit of percentage change from baseline. The corresponding inter-quartile ranges are -50.0 to 10.0 and -30.0 to 40.0. An inter-quartile range describes the central spread of observations; it does not by itself provide a confidence interval for the group summary or for a difference between groups.

The endpoint is relevant to the study’s stated objective because it directly measures change in proteinuria. However, the registry does not report a numerical between-group contrast, uncertainty interval, or test for this primary endpoint. The group summaries alone therefore do not establish the precision of the treatment comparison. Also, although the registry labels the summary parameter as a mean, it reports an inter-quartile range; the record does not explain that presentation. The endpoint’s measurement rationale is general, while the analysis details specific to this trial are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on the type of summary and comparison being reported. The registry gives arm-level summaries for the primary endpoint and mean-and-standard-deviation summaries for three secondary outcomes. These forms of reporting answer different questions and have different limits. The primary arm summaries describe the observed distributions as presented; the secondary calculations estimate unadjusted differences between group means from the posted summary statistics.

What do group summaries tell us?

For the primary endpoint, the registry reports percentage-change values with inter-quartile ranges. An inter-quartile range describes the span covering the middle portion of the observed distribution. It conveys spread, but it does not directly express uncertainty about a group mean or treatment contrast. The record labels the primary parameter as a mean even though the stated dispersion is an inter-quartile range. Because no clarification is given, that labeling ambiguity should remain visible rather than be resolved by assumption.

The primary summaries are -23.0 in the pentoxifylline arm and -4.0 in the placebo arm. The ranges are -50.0 to 10.0 and -30.0 to 40.0. Those figures describe each arm separately. A treatment comparison ordinarily needs an estimate of the between-group contrast and a measure of its uncertainty. Neither is reported for this endpoint, so the summaries do not supply the full inferential answer to the primary question.

How should the secondary comparisons be read?

The recalculated secondary comparisons use each arm’s posted mean, standard deviation, and outcome count to form an unadjusted mean difference. The difference is oriented as pentoxifylline relative to placebo. A confidence interval describes the range of values compatible with the estimate under the method’s assumptions; an interval that includes zero does not provide strong evidence of a difference in that simple comparison. This is a general explanation of interval interpretation, not a claim about the trial’s planned analysis.

For eGFR, the recalculated difference is 2.54 ml/min per 1.73m2, with an interval from -3.421 to 8.501 and p = 0.404. For creatinine, it is -0.01 mg/dL, with an interval from -0.066 to 0.046 and p = 0.726. Each interval includes zero. For fasting glucose, the recalculated difference is -18.4 mg/dL, with an interval from -32.13 to -4.669 and p = 0.009; this interval does not include zero. These are simple, unadjusted calculations, not results of analyses reported by the sponsor. The registry record does not report adjusted analyses or a statistical analysis plan against which to compare them.

A p-value describes how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor does it describe the size or clinical importance of an effect. The secondary p-values are unadjusted. Because several outcomes are considered, a low unadjusted p-value should not be interpreted as if it were the result of a single isolated test. The record does not report whether any multiplicity procedure was planned or used.

Why does variability matter?

Standard deviations describe dispersion around a mean. Larger variability generally makes a mean difference less precisely estimated when other features are held constant. This is a general statistical principle. The posted standard deviations differ across outcomes, so the degree of precision also differs. The confidence intervals reflect both the observed differences and the uncertainty from variation and group counts under the recalculation method.

Over-dispersion is a general concern when data vary more than a statistical model assumes. If a model understates variability, it can make intervals too narrow and tests too optimistic. The registry does not report a model for the primary endpoint, diagnostics, or an over-dispersion assessment. The primary inter-quartile ranges are descriptive and do not permit such an assessment on their own.

What do the planning illustrations mean?

The planning illustrations are not observed power. They use the observed effect as a starting point and show hypothetical participants per arm for 80% or 90% power at a two-sided significance level of 0.05, assuming equal allocation and a normal approximation. The illustrations also consider detecting 100%, 75%, or 50% of the observed effect. They are scenario calculations, not evidence that the trial was designed around those assumptions, and not a retrospective measure of how likely the trial was to detect an effect.

Planning estimates based on an observed effect can be unstable, especially when an observed effect is imprecisely estimated. Smaller target effects require larger planned groups under the stated approach. These illustrations do not establish what effect is clinically meaningful, and they do not repair the absence of a primary comparative estimate. The trial’s own sample-size justification, target effect, and design assumptions are not reported in the registry record.

Finally, none of these calculations resolves questions about missing observations, adherence, analysis populations, or adjustment for baseline differences. Those are features of the analysis plan and data, not quantities that can be inferred from group-level summaries alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, but it does not report a statistical analysis plan, a multiplicity strategy, or the order in which secondary hypotheses were to be tested. Multiple outcome assessments create a general risk that at least one unadjusted result will appear unusual by chance. The recalculated secondary p-values do not account for that possibility. The record does not say whether the investigators adjusted for multiple comparisons, treated secondary results as exploratory, or used another prespecified approach.

Information about missing data is also limited. The enrollment is 174, while the posted arm-specific outcome counts are 52.0 and 70.0 for the primary endpoint and the continuous secondary outcomes. Safety counts use 87 participants at risk in each arm. These figures describe the respective registry entries; they do not explain who contributed to each analysis or why the outcome counts differ from enrollment. Reasons for missing observations, withdrawals, exclusions, and outcome-specific availability are not reported in the registry record. No imputation method or sensitivity analysis is reported.

The analysis populations are not identified. The record does not say whether the posted outcomes use an intention-to-treat, per-protocol, or other population, and it does not describe how participants with incomplete follow-up were handled. Baseline characteristics for those included in each outcome analysis and adjustments for baseline values are not reported. These omissions matter because group-level results can be affected by which participants contribute data and how incomplete measurements are treated.

Interim analyses, stopping rules, and any changes to the analysis plan are not reported in the registry record. Nor are protocol deviations or adherence analyses described. These absences do not prove that such procedures were not conducted; they mean that the registry entry does not provide the information needed to assess them. The primary endpoint also lacks a reported between-group estimate, which prevents evaluation of its precision regardless of how the secondary outcomes are handled.

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 3% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 87 participants at risk in each arm. For other adverse events, it reports 20 affected among 87 at risk in the pentoxifylline arm and 3 among 87 at risk in the placebo arm. These are counts as posted, not comparative risk estimates. No percentages or rates are calculated.

The record does not provide the serious-event terms, and the list of top serious terms is empty. The death counts are null, so deaths are not reported in the registry record. The definitions of serious and other adverse events, the collection period, event severity, and any assessment of relatedness are not reported. It is also unclear from this entry whether the other adverse-event counts refer to participants with at least one event or to events themselves; the record labels them as affected participants but gives no further detail.

These figures should therefore be read as limited descriptive safety reporting, not as a complete assessment of comparative safety. A zero serious-event count in the posted data does not establish that no serious event occurred outside the reported record or that risks are equivalent. The differences in the other-event counts cannot by themselves establish causation. Detailed event descriptions and analysis methods are not reported in the registry record.

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

The registry’s primary outcome summaries describe percentage change in urine protein-to-creatinine ratio from baseline to 24 weeks in the two groups. They show the posted arm values and their inter-quartile ranges, but they do not include a direct treatment contrast or an uncertainty interval for that contrast. As a result, the primary result does not establish how precisely the groups differ. It should not be translated into a claim that pentoxifylline does or does not have an effect.

The secondary calculations provide more direct, but still limited, comparisons. They are unadjusted recalculations from posted summary statistics rather than reported sponsor analyses. Two of the three intervals include zero; the fasting-glucose interval does not. These results do not substitute for a primary endpoint analysis, and the registry does not report how multiple outcome testing was handled. Their statistical pattern alone cannot determine clinical importance.

The distinction between statistical evidence and clinical meaning is important. A confidence interval describes uncertainty under a method and its assumptions. It does not decide whether a difference matters to patients or practice. The registry does not provide a threshold for a clinically meaningful change in proteinuria, detailed participant characteristics, or a primary comparative estimate to evaluate against such a threshold. No treatment recommendation follows from these posted summaries.

The record also leaves key interpretive questions unanswered: which analysis populations were used, how missing outcomes were handled, whether baseline measurements were adjusted for, and whether any interim or sensitivity analyses were conducted. The listed enrollment and outcome counts do not answer those questions. The safety entry is similarly limited by absent event definitions and details.

In short, the registry offers descriptive primary-arm data, a small set of secondary summaries that support simple unadjusted comparisons, and limited adverse-event counts. The information is insufficient to make a firm inferential conclusion about the primary treatment comparison or to assess all aspects of trial conduct and reporting.

13. Why This Trial Matters Statistically

This trial illustrates why a reported group result and a treatment comparison are not interchangeable. The primary endpoint is directly connected to the study objective, but the registry reports arm summaries without a between-group estimate or measure of its precision. Readers therefore cannot use the posted primary figures alone to assess the strength of evidence for a difference. Reporting a contrast with its uncertainty would be essential for interpreting the main question.

The entry also shows how outcome labels and summary measures affect interpretation. The primary parameter is labeled as a mean, while the dispersion is given as an inter-quartile range. That combination may be meaningful in a particular reporting convention, but the registry does not explain it. Clear definitions of estimands and summaries help readers understand what a statistic represents and whether groups are being compared on the same basis.

The secondary outcomes demonstrate another statistical issue: multiple results can create a tempting but unreliable focus on whichever unadjusted finding looks most notable. The record lists several outcomes, posts numeric results for some, and does not report whether multiplicity was addressed. Prespecification and transparent reporting help separate confirmatory evidence from exploratory patterns.

Finally, the registry presents differing counts across enrollment, outcome results, and safety reporting without explaining the analysis populations or missingness. Those counts should be interpreted as specific to their entries, not as a complete account of participant flow. Together, these features make the record a useful example of why transparent primary analyses, clear denominators, and documented missing-data and multiplicity procedures matter when evaluating randomized trials.

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.

Several limitations are specific to the information recorded for this study. Most importantly, the primary endpoint has arm-level percentage-change summaries but no reported comparative estimate, confidence interval, or p-value. The registry also labels the primary summary parameter as a mean and its dispersion as an inter-quartile range, without explaining the presentation. This limits interpretation of both the summary and the spread.

Outcome counts are lower than the stated enrollment in the posted primary and secondary results, but the registry does not explain the relationship. The safety entry uses different arm-specific at-risk counts. No participant flow, reasons for missing outcomes, analysis population definitions, or missing-data methods are reported. This makes it difficult to assess whether the posted groups represent the randomized participants and how incomplete follow-up may have affected results.

The secondary comparisons are simple, unadjusted recalculations. The registry lists no reported analyses and does not document a statistical analysis plan, baseline adjustment, multiplicity handling, or sensitivity analyses. Numerical results are not posted for all named secondary outcomes. Consequently, the secondary results should not be treated as a complete planned analysis.

Safety reporting is also sparse: serious adverse-event counts are zero in both arms, but event definitions and terms are not provided, death counts are null, and details for other adverse events are limited. The entry does not provide information on adherence or protocol deviations. These are limitations of the registry record; they do not establish whether details exist elsewhere. Such details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Pentoxifylline on Proteinuria in Korean Type 2 Diabetic Patients — NCT01382303.
• Registry record last updated 2017-06-16; status last verified 2017-03.
• Results first posted 2017-06-16.
• 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 record identifies a completed phase 4, randomized, double-blind, parallel-group multicenter study of pentoxifylline versus placebo in Korean patients with type 2 diabetes. The stated primary outcome is percentage change in urine protein-to-creatinine ratio from baseline to 24 weeks. The posted arm summaries are -23.0 for pentoxifylline and -4.0 for placebo, with inter-quartile ranges of -50.0 to 10.0 and -30.0 to 40.0. No direct primary comparison is reported.

Three secondary outcomes have posted continuous summaries, from which simple unadjusted comparisons can be recalculated. The registry lists no sponsor-reported analyses and does not report multiplicity or missing-data methods. Safety reporting includes zero serious adverse events among 87 at risk in each arm and other adverse events affecting 20 among 87 and 3 among 87, respectively. Event details and analysis-population explanations are not reported in the registry record.