Safety and Efficacy Study of a New Intermittent Pneumatic Compression Device to Treat Patients With Peripheral Arterial Disease (PAD) Stage II: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of a New Intermittent Pneumatic Compression Device to Treat Patients With Peripheral Arterial Disease (PAD) Stage II (NCT00762086), a randomized na study. The primary outcome is Absolute Claudication Distance (ACD).

2. Clinical Question

The trial asked whether absolute claudication distance differed between participants assigned to an intermittent pneumatic compression device and those assigned to medication and standard walking exercises. The registry identifies the population as people with peripheral arterial disease (PAD) stage II and labels the primary outcome population as the ITT cohort.

The posted results give a mean difference of 53.58 meters, with a confidence interval from 7.055 to 100.1 meters and an unadjusted p-value of 0.024. These figures describe the recorded comparison; they do not by themselves establish how the device performs for an individual or in other populations. The registry record does not report secondary outcome results.

3. Trial Design

This was a prospective, randomized, multicenter, parallel-group clinical trial, according to the official title and registry design entries. The record lists single masking. It does not say which people involved in the trial were masked, so the masking arrangement cannot be described more specifically. The trial status is completed.

The registry reports enrollment of 67 participants. It assigns 39 to the Treatment Group and 28 to the Control Group. The treatment group received the AngioPress intermittent pneumatic compression device. The control group received aspirin/clopidogrel as spelled in the arm description and standard walking exercises; elsewhere, the record describes this as medications and standard walking exercises. Further details about treatment delivery, adherence, or concomitant care are not reported in the registry record.

The registry lists the study start as 2009-03 and primary completion as 2012-01. The sponsor is Mego Afek Ltd. The phase is listed as NA; the record does not explain that designation. It lists peripheral arterial disease as the condition and gives the trial title as a study of the device in patients with PAD stage II.

Random allocation can help make groups comparable at the start of a trial, but the record does not describe the allocation sequence, concealment, or the methods used to maintain masking. The registry also does not report the original sample-size justification, trial protocol, or detailed statistical analysis plan. Those omissions limit how fully the planned design can be compared with the posted results.

4. Participant Flow and Accounting

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

Before assignment: Subjects were required to be treated with Aspirin/Clopidogrel for at least one week priot to 1st treatment

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT cohort

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 Absolute Claudication Distance (ACD), measured over 3 months.

The primary endpoint was Absolute Claudication Distance (ACD), measured in meters at 3 months. The registry describes it as the distance a participant walked on a treadmill until leg pain made the participant unable to continue. It identifies the outcome population as the ITT cohort and the summary measure as a least-squares mean with standard error as the dispersion measure.

Walking distance is a continuous measure: it can take a range of values rather than placing each participant into a simple category. It captures how far a participant can walk before the specified symptom limits further walking. In this trial, the registry used the treadmill distance as its primary measure for evaluating the device in people with PAD stage II. This describes the role of the measure in the study, not a judgment about its clinical importance or whether any particular distance is adequate for an individual.

The registry posts one outcome measure and gives the assessment time as 3 months. It does not report further measurement details, such as treadmill protocol settings, how repeat measurements were handled, or how missing endpoint observations were treated. Those details matter when interpreting how consistently the measurement was obtained and which participants contributed to the posted group estimates.

7. Results Posted in the Registry

• Treatment Group: mean 54.37 versus 0.79 on control; difference 53.58 (95% CI 7.05 to 100.11), standardized effect d = 0.56; z-test p = 0.024.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous, so the registry summarizes it with means rather than event counts or proportions. A mean is an average across the observations included in an analysis. The posted group summaries are identified as least-squares means, a term generally used for model-based averages. The registry does not state the model specification, so the precise adjustments underlying those means are not reported in the registry record.

The main comparison is a mean difference. It expresses the estimated separation between the treatment and control group averages in the endpoint’s units, meters. The posted estimate is 53.58 meters. A difference is easier to interpret in the endpoint’s original units than a unitless standardized measure, although its practical meaning depends on clinical context that is not specified by the statistical result alone.

The record also includes a standardized effect estimate, d = 0.559, and a pooled standard deviation of 95.89. These are derived comparison statistics in the posted record; the pooled standard deviation is marked as approximate. A standardized effect expresses the group difference relative to a measure of variability, which can help compare effects measured on different scales. It does not replace the original-unit estimate, and the registry does not provide a clinical threshold for interpreting its size.

The arm-level dispersion is listed as standard error: 15.38 for the Treatment Group and 18.09 for the Control Group. A standard error describes the sampling uncertainty of an estimated mean, rather than the spread of individual participant measurements. It generally becomes smaller when an estimate is based on more information, but its interpretation depends on how the estimate and analysis population were constructed. The record identifies the outcome population as ITT but does not report the number with observed endpoint data or the missing-data method.

The confidence interval gives a range of values reasonably compatible with the data and the assumptions of the analysis. For this comparison, the interval is 7.055 to 100.1 meters. A narrower interval would indicate greater precision; a wider interval indicates greater uncertainty about the size of the difference. The interval is not a range containing a specified proportion of individual participants’ walking distances. It describes uncertainty in the estimated group difference.

The posted p-value is unadjusted and equals 0.024. In general, a p-value describes how unusual the observed data, or more extreme data, would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The registry does not describe the model assumptions behind this p-value, or report adjusted p-values.

The planning illustrations use the observed effect as a starting point, with alternative rows targeting 100%, 75%, and 50% of that effect. They assume a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Such calculations illustrate how a planned sample size can change when the target effect changes, under those stated assumptions. They are not a record of the trial’s original design decisions.

General statistical concepts help clarify why these summaries may not tell the entire story. Continuous outcomes can have skewed distributions or unequal variability across groups. If variability is greater than a model expects, standard errors and p-values based on an unsuitable model may not reflect uncertainty well. Over-dispersion is a related concern for count outcomes, where observed variation exceeds the model’s expectation; it is not itself a summary of this continuous walking-distance endpoint. The registry does not report distribution checks, robust methods, or sensitivity analyses for this outcome.

Randomization is a design feature intended to support a fair comparison by assigning participants to groups by chance. In general, it can reduce systematic differences in prognostic factors at baseline, but it cannot guarantee balance, particularly in a trial of this size. Baseline characteristics are not reported in the registry record, so group comparability cannot be evaluated from the posted information. The record also does not give allocation concealment procedures or details of masking beyond the single-masked designation.

The outcome is labeled as being measured in an ITT cohort. In general, an intention-to-treat analysis seeks to analyze participants in the groups to which they were randomized, regardless of treatment adherence. The registry’s label alone does not explain how participants with missing outcomes were handled, how deviations were treated, or whether the analysis followed a prespecified plan. No analysis descriptions are posted, and the record does not report secondary results, interim analyses, or the original statistical analysis plan. These unknowns limit independent assessment of the analysis choices.

10. Confidence Intervals and Precision

The mean-difference estimate is 53.58 meters, and its confidence interval extends from 7.055 to 100.1 meters. The interval represents uncertainty about the group difference, not the range of individual outcomes. Its lower and upper limits are both above zero, while the distance between them indicates that the estimate’s magnitude remains imprecise.

In general, a confidence interval is constructed by a statistical method that accounts for sampling variation under specified assumptions. If the same design and method were repeated many times, intervals constructed in that way would have a stated long-run coverage property. This does not mean there is a 95% probability that this particular interval contains the true difference, nor does it imply that all values inside the interval are equally likely.

The posted interval provides more context than a single point estimate: it shows that the estimate is compatible with a range of differences. The registry lists standard errors of 15.38 and 18.09 for the Treatment Group and Control Group. These values relate to uncertainty in the group estimates, while the confidence interval relates to uncertainty in their comparison. The record does not describe the precise method used to calculate the interval.

Precision depends on more than the number enrolled. It can also depend on outcome variability, the analysis method, and how many participants have usable endpoint measurements. The registry reports enrollment of 67 and arm sizes of 39 and 28, but does not report endpoint completeness or the missing-data approach. The confidence interval should therefore be interpreted alongside those limitations rather than as a complete measure of reliability.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original sample-size rationale. For this continuous outcome, the figures are participants per arm, not total event counts. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to a stated fraction of the observed effect.

The 80% power column describes the number of participants per arm indicated by the planning calculation for an 80% chance of detecting the target effect under the assumptions, if that effect and the model assumptions are correct. The 90% power column uses the same general interpretation with a higher target chance of detection. Higher planned power generally requires more participants, all else being equal.

The rows vary the target from 100% of the observed effect to 75% and 50% of the observed effect. The calculations show that smaller effects need more participants to detect under the stated assumptions. For example, the row for 100% of the observed effect gives 51 participants per arm for 80% power and 68 for 90% power; the row for 75% gives 90 and 120; the row for 50% gives 202 and 270. These are planning values, not observed enrollment requirements or a reconstruction of the trial’s design.

The sample-size curve should be read in the same planning context: it illustrates how the required number changes as the target effect changes. These calculations are not observed power. The registry record does not report the original sample-size assumptions, and the posted enrollment of 67 should not be interpreted by comparing it with a single planning row as though that row were the trial’s prespecified target.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 53.582; pooled standard deviation σ = 95.889.
2. n = 2 × (1.96 + 0.842)² × 95.889² / 53.582² = 50.3, rounded up to 51 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 53.582                      # observed difference in means
sigma <- 95.888722790432                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(762086)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 51 (80% power), 68 (90% power)
 75% of observed effect: n per arm = 90 (80% power), 120 (90% power)
 50% of observed effect: n per arm = 202 (80% power), 270 (90% power)
power.t.test: 51.3 
Simulated power at n = 51 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, Absolute Claudication Distance at 3 months, and reports no secondary outcome results. It records 0 analyses. This means the record does not offer a set of analysis descriptions through which to assess which models or comparisons were conducted. The single posted comparison has an unadjusted p-value of 0.024.

Multiplicity arises when multiple outcomes, time points, groups, or analyses are tested. In general, conducting many tests can increase the chance of finding at least one apparently unusual result by chance. Statistical plans can address this in different ways, but the registry record does not report whether multiplicity was considered, what testing hierarchy might have been planned, or whether adjustments were made. The absence of that information should not be replaced by an assumption that no other tests were conducted.

The outcome population is labeled ITT cohort. The record does not define that population in detail or provide a participant flow, number of endpoint observations, or reasons for missing data. It does not report imputation, exclusion rules, sensitivity analyses, or how treatment deviations were handled. These details matter because missing outcome measurements can affect the analyzed groups and the uncertainty of their estimates.

The original protocol, sample-size justification, and detailed statistical analysis plan are not reported in the registry record. Nor are interim analyses or stopping rules reported. Therefore, it is not possible to determine from the registry whether the posted outcome and analysis followed a prespecified plan, or whether unreported analyses influenced the reported comparison.

14. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypertensive crisis (2.6%), congestive heart failure (2.6%).

The registry reports serious adverse events affecting 2 participants in the Treatment Group, with 39 at risk, and 0 participants in the Control Group, with 28 at risk. For other adverse events, it reports 2 affected in the Treatment Group and 0 in the Control Group, using the same group sizes at risk. These are reported counts; they should not be treated as evidence that an event was caused by the assigned intervention.

The most frequent serious-event terms listed are Hypertensive Crisis and Congestive heart failure, each reported as 2.6%. The record does not give further event-level detail, including timing, participant overlap, or relationship to treatment. Deaths are not reported in the registry record. The absence of a reported death figure is not the same as evidence that no deaths occurred.

These safety counts are descriptive and involve small groups. They do not, on their own, establish a difference in risk between groups. The registry record does not provide a fuller safety analysis or enough context to determine causality.

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

The result describes a difference in treadmill walking distance between two randomized groups at 3 months. The posted mean difference is 53.58 meters in the direction of a higher group estimate for the Treatment Group. The confidence interval, from 7.055 to 100.1 meters, shows that the exact size of the estimated difference is uncertain. The unadjusted p-value is 0.024, but statistical evidence against a null difference does not by itself establish clinical importance.

The finding applies to the trial’s recorded population and setting: patients with peripheral arterial disease stage II assigned to the device group or the medication-and-exercise control group. The record identifies enrollment as 67 and gives the primary endpoint population as ITT. It does not provide detailed eligibility criteria, baseline characteristics, adherence information, or endpoint completeness. Those omissions make it difficult to judge how closely the participants and trial conduct match other settings.

The result does not show how each participant’s distance changed from baseline, because the registry record does not provide a baseline outcome or change-from-baseline result. It also does not establish which component of the treatment regimen may relate to the observed group difference. The intervention and control conditions differ in their described components, and the registry does not provide analyses that separate their contributions.

The posted comparison does not establish that the device will have the same effect in other populations, with different care practices, or over other time periods. The primary endpoint is reported at 3 months; longer-term outcomes are not reported. No secondary outcome results are listed. The safety counts are limited and descriptive, and event attribution is not reported. These points define what can and cannot be concluded from the registry entry without making a treatment recommendation.

16. Why This Trial Matters Statistically

This trial offers a useful statistical example of how an estimated group difference, its uncertainty, and the design details need to be read together. The point estimate of 53.58 meters is informative about the direction and estimated size of the primary comparison, while the interval from 7.055 to 100.1 meters makes clear that a range of effect sizes remains compatible with the analysis.

The registry identifies a randomized, parallel-group design and a continuous primary outcome measured in meters. That lets the comparison be expressed in the measure’s original units. The arm sizes, 39 and 28, are also important context for considering the amount of information available. The record does not describe the analysis model or outcome completeness, so the reported summaries cannot be fully audited against those aspects of the study.

Planning illustrations are another useful statistical feature. They demonstrate that required sample sizes depend on the effect a study is intended to detect: targeting a smaller effect calls for more participants under the same assumptions. Because these figures are based on the observed effect and are not the trial’s original design rationale, they should be used to understand the assumptions rather than as a verdict on the trial’s adequacy.

Finally, the record shows why statistical evidence and clinical interpretation are distinct. A p-value and confidence interval describe aspects of uncertainty under an analysis; they do not decide whether an effect matters to patients or settle safety questions. Reporting details about methods, missing data, and safety would make the result easier to evaluate.

17. 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 does not report the detailed statistical model behind the least-squares means, the mean difference, or the confidence interval. It also does not specify whether the analysis adjusted for baseline characteristics or other covariates. The posted standard errors and the note that the pooled standard deviation is approximate do not resolve those uncertainties.

Although the primary outcome population is labeled ITT, the record does not give the number of participants with observed endpoint measurements or explain how missing observations were handled. There is no participant flow or account of withdrawals in the posted information. The trial’s original sample-size justification, protocol, and analysis plan are also not reported, nor are interim analyses.

The registry describes the trial as single-masked but does not identify who was masked. It does not report allocation concealment, baseline characteristics, adherence, or additional details of treatment delivery. The design is described as multicenter, but the number or identity of centers is not reported in the registry record.

Only one outcome measure is listed, and no secondary results are posted. The serious and other adverse-event counts are limited; deaths are not reported, and the relationship between events and assigned intervention is not given. These limitations mean the record supports a focused reading of the posted 3-month endpoint comparison, but not a complete assessment of trial conduct, all outcomes, or safety.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of a New Intermittent Pneumatic Compression Device to Treat Patients With Peripheral Arterial Disease (PAD) Stage II — NCT00762086.
• Registry record last updated 2012-08-31; status last verified 2012-08.
• Results first posted 2012-08-27.
• 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.

21. Record Summary

The registry describes a completed, randomized, single-masked, parallel-group trial of an intermittent pneumatic compression device in patients with peripheral arterial disease stage II. Enrollment was 67, with 39 participants in the Treatment Group and 28 in the Control Group. The primary outcome was Absolute Claudication Distance in meters at 3 months, assessed in the ITT cohort.

The posted mean difference was 53.58 meters, with a confidence interval from 7.055 to 100.1 meters and an unadjusted p-value of 0.024. The record lists serious adverse events affecting 2 participants in the Treatment Group and 0 in the Control Group; deaths are not reported. Detailed analysis methods, missing-data handling, secondary outcome results, and the original sample-size rationale are not reported in the registry record.