Cilostazol After Lower Extremity Arterial Revascularization Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cilostazol After Lower Extremity Arterial Revascularization Trial (NCT02374957), a randomized phase 4 study. The primary outcome is Change in Quality of Life in Relation to Use of Cilostazol After Lower Extremity Revascularization (EQ-5D Sum Score) at 6 Weeks.

2. Clinical Question

CLEAR was designed to collect quality-of-life information in patients undergoing peripheral revascularization. Its stated purpose was to use these data to help determine the sample size for a future trial comparing cilostazol with usual care without cilostazol. The registry describes a randomized, parallel-group comparison, but reports no masking.

The primary endpoint is a continuous EQ-5D sum score, with higher values indicating worse health state. The question is therefore about measured change in a patient-reported health-status score, not only about whether a graft is open or occluded. Graft patency, assessed by duplex scan after the intervention, is listed as a secondary outcome.

The record identifies the primary endpoint as change at 6 weeks and says the questionnaire was completed at baseline, 6 weeks and three months. It also explains that separate change scores are estimated at each follow-up time point. The posted record does not provide the resulting arm-specific means, change estimates, uncertainty intervals or a single comparison for this multi-time-point outcome. Consequently, it does not establish the direction or size of any observed difference in quality-of-life scores.

3. Trial Design

CLEAR is listed as a phase 4, randomized, parallel-group trial with no masking. Wake Forest University Health Sciences is named as the sponsor. The record gives enrollment as 20 and describes an intended allocation of ten participants to cilostazol and ten to control. The listed status is terminated; the reason for termination is not reported in the registry record.

Participants assigned to the cilostazol arm were to receive 100 mg twice daily for 90 days. The control arm is described as receiving no cilostazol. The trial’s stated purpose was to collect quality-of-life data after peripheral revascularization and use those data to plan the sample size of a later trial. It was therefore intended to inform planning, rather than to serve as a definitive evaluation of a treatment effect.

The primary outcome is the change in the EQ-5D sum score at 6 weeks, with the timeframe also described as baseline and 6 weeks. The measure is collected at baseline, 6 weeks and three months, and the record notes that separate change scores are estimated at each follow-up. The secondary outcome listed is graft patency, determined as opened or occluded by duplex scan after the intervention.

The registry describes 11 outcome measures and 7 analyses. The primary outcome is not reduced in the posted material to one comparison, because it has several categories or time points. The full protocol, detailed statistical analysis plan, eligibility criteria, recruitment flow, actual allocation sequence, and reasons for terminating the trial are not reported in the registry record. Those omissions limit how fully the design and its implementation can be reconstructed from the posted information.

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: Only patients with data collected at each pair of time points are included in the analysis.

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 in Quality of Life in Relation to Use of Cilostazol After Lower Extremity Revascularization (EQ-5D Sum Score) at 6 Weeks, measured over Baseline and 6 weeks..

The primary endpoint is change in the EQ-5D sum score at 6 weeks, compared with baseline. EQ-5D is a standardized measure of generic health status. Its descriptive system covers mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Participants select the level that reflects their health state for each dimension, and the dimension scores are combined into a sum score.

The recorded score ranges from 5 to 25, with higher scores indicating a worse health state. This direction matters when interpreting any future comparison: a higher score does not represent better health on this measure. The score is continuous, and the registry identifies the summary measure as a mean with standard deviation.

Quality-of-life measurement is relevant to the trial’s stated planning purpose because it captures reported health status after revascularization, rather than only a procedural or vessel-related outcome. The record says EQ-5D was completed at baseline, 6 weeks and three months, with separate change scores estimated for each follow-up. The primary endpoint title specifically identifies the 6-week change. The registry record does not report the observed scores or changes, so their magnitude and precision cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What the endpoint summary represents

The registry classifies the primary measure as continuous and summarizes it using a mean and standard deviation. A mean describes the average score in the analyzed group; a standard deviation describes how spread out individual scores are around that average. These are descriptive summaries. By themselves, they do not show whether groups differ reliably, nor do they express the uncertainty in a comparison.

The endpoint is a change score, with baseline and 6 weeks named as the primary timeframe. Change scores use each participant’s measurements at the relevant time points to represent movement in the score. The record says separate change scores are estimated at each follow-up time point. It does not report the actual estimates, the between-group contrast, or the method used to test that contrast. Those analysis details are not reported in the registry record.

Why uncertainty matters

General statistical explanation: an estimate from a sample is uncertain because a different set of participants could produce a different estimate. A confidence interval is a way to describe that uncertainty around an estimate. A narrow interval indicates greater precision than a wide interval, but it does not by itself establish clinical importance. The registry record does not report a confidence interval for the primary outcome, so the precision of any difference cannot be assessed.

General statistical explanation: a p-value, when used, summarizes how compatible observed data are with a specified null model and assumptions. It is not the probability that the null hypothesis is true, and it does not convey the size or importance of an effect. No primary-outcome p-value is reported in the registry record. The record also does not state the test or model used for the primary comparison.

What the sample-size illustrations mean

The planning illustrations use the assumptions described in the registry: a two-sided significance level of 0.05, equal allocation, a normal approximation, and a target effect expressed as a stated fraction of the observed effect. For continuous outcomes, the illustrations are expressed as participants per arm for 80% power or another stated power level where shown. These are planning scenarios, not descriptions of the number analyzed or the observed power of CLEAR.

General statistical explanation: a sample-size calculation depends on assumptions about the effect to detect, the variability of the measure, the significance level and the desired power. Changing those assumptions can change the planning estimate. An illustration based on a fraction of an observed effect shows how a future study’s size would vary under that assumed target; it does not establish that the target is clinically important or that the effect estimate is stable. The registry record does not report a protocol-based sample-size justification for CLEAR, and the planning calculations should not be mistaken for one.

Why variability and analysis choices matter

The standard deviation is relevant because more variable scores generally make a group comparison less precise for a given amount of information. General statistical explanation: when data are more dispersed, it can be harder to distinguish a group difference from variation among individuals. The registry identifies standard deviation as the measure of dispersion but does not provide the observed values or state how variability was handled in the analysis.

The primary outcome is measured at multiple time points, and the registry refers to change scores at each follow-up. General statistical explanation: multiple time points create choices about which comparison is primary, how repeated measurements are modeled, and how to account for making several comparisons. The posted primary outcome has several categories or time points and is not reduced to one comparison. The analysis approach for repeated measures, and any adjustment for multiplicity, are not reported in the registry record.

The record states that only patients with data collected at each pair of time points are included in the analysis. This describes a pairwise complete-data approach for each change score: a participant needs data at both relevant measurements to contribute to that change analysis. General statistical explanation: this approach can mean that the set of participants analyzed differs across time-point comparisons when data are incomplete. The registry does not report the number contributing to each comparison, the amount or reasons for missingness, or methods used to address missing data.

Finally, the posted record lists 11 outcome measures and 7 analyses, but does not provide the full statistical analysis plan. The exact models, covariate adjustments, handling of assumptions, and analysis populations are not reported in the registry record. Without those details and the numerical outcome results, readers should treat the posted description as a summary of intended measurement and planning, not a complete account of inferential methods.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures and 7 analyses. It describes the primary measure at baseline, 6 weeks and three months, with separate change scores at each follow-up. The posted primary outcome has several categories or time points and is not reduced to one comparison. This makes it important to know which time point and contrast were designated as primary for inference and how multiple comparisons were handled. Those details are not reported in the registry record.

General statistical explanation: when several outcomes, time points or comparisons are examined, the chance of at least one apparently unusual result can increase if no multiplicity strategy is used. Methods such as defining a single primary contrast in advance or adjusting inference can address different aspects of this issue. The record does not identify such a strategy, so no claim about multiplicity control can be made.

The outcome population is described as patients with data collected at each pair of time points. Thus, the number analyzed for a change score may depend on availability at both measurements. The record does not report the analysis count for the primary comparison, missing-data counts by time point, reasons for missingness, or any imputation or sensitivity analysis. The allocation population and the analysis population are not fully described in the posted record.

These gaps matter when interpreting estimates: the extent to which missing observations or multiple comparisons affect results cannot be assessed without the relevant counts and analysis plan. The reason for termination and its relation, if any, to outcome collection are also not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: amputation (22.2%), hemodialysis (11.1%), suspected mi (11.1%), other non-cvd (10.0%).

The registry reports serious adverse events for the cilostazol and control groups. In the cilostazol group, 3 of 10 participants are listed as having a serious adverse event; in the control group, 3 of 9 are listed. Deaths are recorded as 0 in the cilostazol group and 1 in the control group. These are participant counts, not an adjusted comparison of risk.

The registry also lists serious-event terms with percentages, including amputation, hemodialysis, suspected MI and other non-CVD events. These entries describe the posted safety record; they do not establish that an event was caused by study treatment. The record does not provide enough detail to clarify the event-level context or the basis for each listed percentage.

These counts should be read cautiously. The denominators shown for safety differ between groups, and the record does not explain the difference. The trial is small, and the posted counts alone cannot provide a precise estimate of comparative safety or support a causal conclusion. The registry does not report a statistical safety comparison or an account of how the events were adjudicated.

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

The registry record establishes that CLEAR was a randomized, parallel-group study intended to collect quality-of-life data after peripheral revascularization. It specifies cilostazol 100 mg twice daily for 90 days versus no cilostazol and identifies change in EQ-5D sum score at 6 weeks as the primary endpoint. It also records safety counts and a secondary graft-patency outcome.

However, the primary outcome results are not reported in the registry record. There are no score summaries, change estimates, treatment contrast or uncertainty interval from which to describe the direction, size or precision of a difference. The posted material therefore does not show whether quality-of-life scores differed between groups, and it cannot support a conclusion that cilostazol improved or worsened the measured outcome.

The trial’s stated aim was to generate information for planning a future study. This is a planning objective, not evidence that the future study’s assumptions have been validated. The sample-size illustrations are hypothetical calculations under specified assumptions and should not be read as observed power or as results of a treatment comparison.

The serious adverse event and death counts are descriptive. Without event-level context, an analysis plan and a formal comparison, they do not establish treatment causation or comparative safety. Likewise, the listed secondary outcome does not have a reported result in the registry record.

In short, the available record describes the study framework and some safety counts, but not the primary efficacy estimates needed to assess the stated quality-of-life question. The status is listed as terminated, while the reason and its implications for the available data are not reported in the registry record.

13. Why This Trial Matters Statistically

CLEAR matters statistically because it illustrates the distinction between a trial intended to inform future planning and a trial that reports a precise treatment comparison. Its stated purpose was to collect quality-of-life data after revascularization and use them to plan a later study. That purpose makes endpoint definition, variability and completeness of follow-up central to interpretation, even though the registry record does not report the resulting outcome estimates.

The EQ-5D sum score is a continuous patient-reported measure with a defined direction: higher scores indicate worse health state. Its measurement at baseline and follow-up allows change to be described, but the registry says that separate change scores are estimated at each follow-up. Without a reported primary contrast and uncertainty interval, readers cannot determine how the observed data might inform the planning objective.

The trial also highlights why analysis populations and missing data matter. The record includes only participants with measurements at each pair of time points in the relevant analysis. If availability differs across time points, the number contributing to each change estimate may also differ; those counts are not reported. This affects how readers judge the representativeness and precision of the estimates.

Finally, the posted sample-size illustrations rely on assumptions and an observed effect, while the primary outcome values themselves are not reported in the registry record. This makes clear that planning calculations are conditional illustrations, not stand-alone evidence about clinical effects. The design and endpoint are described, but the missing results and analysis detail prevent a full statistical assessment.

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 main limitation for interpretation is that the registry record does not report the primary EQ-5D results. It provides no analyzed means, standard deviations, change estimates, group contrast or confidence interval. The size and precision of any difference therefore cannot be assessed from the posted information.

The record describes multiple follow-up times and says change scores are estimated separately, but the primary outcome is not reduced to one comparison. The precise inferential target, statistical test or model, and any approach to multiplicity are not reported in the registry record. The statistical analysis plan is not available in the information.

Only patients with data at each pair of time points are included in the relevant analysis, but the numbers included at each follow-up, amount of missing data, reasons for missingness and any sensitivity analyses are not reported. This prevents assessment of whether incomplete follow-up could affect the composition of the analyzed groups.

The record lists enrollment as 20 and status as terminated, but does not report the reason for termination or whether all planned observations were collected. Safety denominators are 10 in the cilostazol group and 9 in control, with no explanation for the difference. The protocol, eligibility criteria, recruitment flow, and detailed account of adverse events are not reported in the registry record.

These limitations do not establish that the results are biased or unreliable; they describe what cannot be evaluated from the posted record. Without outcome estimates and further methodological detail, conclusions about the primary comparison, missingness, multiplicity and safety remain limited.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cilostazol After Lower Extremity Arterial Revascularization Trial — NCT02374957.
• Registry record last updated 2018-11-23; status last verified 2018-11.
• Results first posted 2018-11-23.
• 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

CLEAR is a phase 4 randomized, parallel-group trial sponsored by Wake Forest University Health Sciences and listed as terminated. The registry describes intended enrollment of 20 participants, with cilostazol 100 mg twice daily for 90 days compared with no cilostazol. Masking is listed as none.

The primary endpoint is change in EQ-5D sum score at 6 weeks; higher scores indicate worse health state. The measure was collected at baseline, 6 weeks and three months, with separate change scores at each follow-up. Graft patency by duplex scan is listed as a secondary outcome.

The registry reports serious adverse event counts of 3 of 10 for cilostazol and 3 of 9 for control, and deaths of 0 and 1, respectively. It does not report the primary outcome estimates, the reason for termination, or detailed methods for the primary analysis in the record.