REVITIVE for the Treatment of Patients With Venous Insufficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for REVITIVE for the Treatment of Patients With Venous Insufficiency (NCT02114307), a randomized na study. The primary outcome is Venous Haemodynamics - Percent Change in Time Averaged Mean Velocity TAMV.

2. Clinical Question

This question concerns a measured haemodynamic outcome over the stated follow-up, rather than a direct measure of how participants felt or functioned. Limb swelling, volume, and clinical symptoms were listed as secondary outcomes, so they address related but distinct aspects of venous insufficiency. The registry record does not establish that a change in the primary measure necessarily corresponds to a change in symptoms or swelling.

The comparison is between assignment to the actual device and assignment to a sham device. It is not a comparison with no device or with another treatment. The registry record identifies the study as randomized and single-masked, but does not say who was masked. That missing detail limits how fully readers can assess the potential for expectations or knowledge of assignment to influence study conduct or measurement.

3. Trial Design

The registry record describes a randomized, parallel-group trial of the REVITIVE IX actual device and a sham device. The listed enrollment was 22. The study status is completed; its recorded start date was 2014-03-01 and its primary completion date was 2014-10-01. The record lists the phase as NA, which is consistent with the device intervention being described as a device rather than a medicine.

Participants in the actual-device group were to receive the true REVITIVE IX device; participants in the comparator group were to receive a sham device. The record calls the masking single, but does not identify the person or people masked. It also does not report how randomization was performed, whether allocation was concealed, or what the sham device involved beyond its designation as a sham.

The primary outcome was a continuous measure: percentage change in time averaged mean velocity in the femoral vein, measured by ultrasound at 0 and 6 weeks. The posted primary summaries list 10.0 participants for the actual-device group and 11.0 for the sham-device group. These outcome-summary counts are not identical to the enrollment figure, and the reasons for the difference are not reported in the registry record. The record does not explain whether the analysis included all randomized participants or only those with outcome measurements.

The registry lists limb swelling, volume, and clinical symptoms as secondary outcomes. It also records 3 outcome measures and 4 analyses. Details of the full analysis plan, including how the study selected its primary analysis and handled secondary outcomes, are not reported in the registry record. The original sample-size rationale and design assumptions are also not reported in the registry record; planning illustrations based on the observed results are a separate exercise and do not describe the original trial design.

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: Patient stayed in the full length of the study. Chronic venous insufficiency (C2-C5 CEAP). Blood pressure \<160/100mmHg. No current foot ulceration

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 Venous Haemodynamics - Percent Change in Time Averaged Mean Velocity TAMV, measured over 0 and 6 weeks.

The primary endpoint is the percentage change in time averaged mean velocity, abbreviated TAMV, in the femoral vein. The record says this haemodynamic measure was assessed using an ultrasound scan, with the stated timeframe of 0 and 6 weeks. The reported group values are mean percentage changes, with standard deviations as the measure of spread.

Venous haemodynamics describe blood-flow characteristics in the vein. TAMV is used as a measurable physiological outcome that can be compared between groups under the trial’s device and sham assignments. Using a continuous measure allows the analysis to describe both the average change and the variation among participants. The standard deviation gives a sense of how dispersed individual measurements were around each group mean; it is not a measure of the precision of the group mean itself.

This endpoint answers a specific physiological question. It does not, by itself, establish the size or importance of any change in symptoms, limb swelling, or everyday function. Those outcomes were listed separately as secondary measures. The record does not report a threshold for a clinically important change in TAMV, nor does it state how such a threshold would be interpreted. Accordingly, the observed group contrast should be read as a comparison of the measured haemodynamic outcome, not as a direct summary of all possible patient experiences.

7. Results Posted in the Registry

• REVITIVE IX: Actual Device: mean 102.40 versus -9.10 on control; difference 111.50 (95% CI 68.68 to 154.32), standardized effect d = 2.23; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Clinical Symptoms

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • REVITIVE IX: Actual Device: mean -11.80 versus 6.40 on control; difference -18.20 (95% CI -40.66 to 4.26), standardized effect d = -0.68; z-test p = 0.112.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between REVITIVE IX: Actual Device and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address related but separate questions. Clinical symptoms are summarized numerically in the record, while limb swelling and volume are listed as outcomes without numerical results in the registry record. Therefore, the full pattern across the listed secondary outcomes cannot be assessed from the available registry reporting. In particular, no conclusion about the direction or magnitude of swelling or volume changes can be drawn from the outcome names alone.

The recalculated clinical-symptom mean difference is -18.2 percentage points, with a confidence interval from -40.66 to 4.262 and an unadjusted p-value of 0.112. The registry’s own one-sided t-test reports p = 0.127. These estimates do not give the same strength of statistical evidence as the primary haemodynamic comparison, and the interval includes zero. The values should be interpreted as uncertain secondary evidence rather than as a definitive account of symptom change.

Secondary outcomes can provide context about whether an observed primary-outcome pattern is accompanied by changes in other domains, but they do not automatically confirm or contradict the primary result. TAMV is a haemodynamic measurement; symptoms and swelling are different outcomes and may not move in parallel. The record does not report a prespecified hierarchy or a method for adjusting secondary tests for multiple comparisons.

When several outcomes or analyses are examined, the chance of observing an apparently notable result among them can increase. Without a reported multiplicity strategy, individual unadjusted secondary p-values carry less weight than a result from a clearly prespecified primary analysis. This caution does not mean the secondary outcomes are uninformative; it means that their interpretation depends on their role in the analysis plan, the completeness of reporting, and the uncertainty in their estimates. Those details are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Changes in Limb Swelling, Volume
• Clinical Symptoms

9. Statistical Interpretation

10. Statistical Methods Explained

What does the mean difference describe?

A mean is the arithmetic average of the measured values in a group. The recalculated primary mean difference compares the actual-device group’s average percentage change with the sham group’s average percentage change. The posted estimate is 111.5 percentage points. This is a difference between group averages, not the percentage change for every participant and not a statement that every participant changed in the same direction.

The primary outcome is continuous, so the group summaries include a standard deviation. A standard deviation describes the spread of individual measurements around the group mean. Larger spread means individual outcomes vary more; it does not, on its own, show whether the mean difference is estimated precisely. Precision also depends on the amount of information available, including the number of observed outcomes.

What does the confidence interval convey?

A confidence interval gives a range of estimates compatible with the data under the method’s assumptions. The recalculated primary interval runs from 68.68 to 154.3 percentage points. It does not mean that individual participants’ changes fall within that range, and it is not a guarantee that the true effect lies inside the interval. It is a way to express uncertainty about the estimated group contrast.

The recalculated intervals use the posted means and standard deviations and are unadjusted. They are not intervals from the registry’s reported rank-based primary test. A confidence interval should be considered alongside the estimate and the analysis method rather than used as a standalone verdict. The registry record does not report a confidence interval for its own primary analysis.

Why do the analyses differ?

The registry reports a Wilcoxon (Mann-Whitney) primary analysis. This rank-based method compares the relative ordering of observations between groups, rather than directly estimating a difference between arithmetic means. It can be useful when a rank-based comparison is chosen for the outcome distribution, but it does not produce the same estimand as a mean difference. The registry reports p = 0.001 for that analysis, without a corresponding estimate or confidence interval.

The recalculation uses group means and standard deviations to estimate an unadjusted mean difference and its interval. It is a simple summary-statistic calculation, not a reconstruction of participant-level data. It cannot account for features that are not represented in those summaries, such as covariate adjustment or the handling of missing measurements. Whether those features were part of the trial’s analysis is not reported in the registry record.

For the secondary clinical-symptom outcome, the registry reports a one-sided t-test. A t-test compares means, while the one-sided specification evaluates evidence in a designated direction. The record does not report a confidence interval for that analysis. The recalculated comparison of means is unadjusted and gives a two-sided interval. Because the analyses differ in directionality and in the information they report, their p-values should not be treated as interchangeable measures.

What does a p-value say?

A p-value describes how incompatible the observed data are with a particular null model, under the assumptions of the test. It does not measure the probability that the null hypothesis is true, the probability that a finding is due to chance, or the importance of an effect. A small p-value can accompany an estimate that is imprecise or not clinically important; an estimate and its uncertainty are needed for interpretation.

The registry’s primary p-value is associated with its Wilcoxon analysis, whereas the recalculated p-value is associated with the mean-based comparison. The distinction matters because tests can target different features of the data. The record does not report whether any adjustment for multiple outcomes or analyses was applied, so the posted p-values should be read as unadjusted evidence unless otherwise specified by the record.

Why does over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. If an analysis assumes less variability than the data contain, uncertainty can be understated and tests can appear more decisive than warranted. The posted primary standard deviations are 50.0 in each group, and the recalculation uses those summaries rather than imposing a separate variance estimate. The record does not describe a formal assessment of over-dispersion or a model-based adjustment for it.

More broadly, the validity of a test depends on how well its assumptions fit the study data and design. A rank-based test and a mean-based calculation offer different summaries; neither resolves missing-data, allocation, or measurement concerns that are not described in the registry record. The participant-level data and fuller analysis documentation are not reported in the registry record, which limits independent assessment of those issues.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 111.5 percentage points, with a confidence interval from 68.68 to 154.3. The interval is entirely above zero, so under the unadjusted mean-based calculation it is compatible with a positive average contrast between the actual-device and sham groups. Its width also matters: it conveys uncertainty about the size of the difference, even though the estimate is separated from zero. It should not be read as a range containing individual participants’ outcomes.

The posted primary group standard deviations are 50.0 for both groups. These describe participant-level variability, while the confidence interval describes uncertainty in the estimated group contrast. The registry’s own Wilcoxon analysis reports p = 0.001, but does not report an effect estimate or confidence interval for that analysis. Thus, the mean-based interval and the registry’s rank-based p-value answer related but not identical statistical questions.

For clinical symptoms, the recalculated interval runs from -40.66 to 4.262 and includes zero. It is compatible with a range of mean differences that includes no difference, as well as values on either side of zero. This indicates less precision about the direction and magnitude of the secondary contrast than the primary mean-based result. The registry’s one-sided t-test result does not come with a recorded interval.

Precision is constrained by the small posted outcome-group counts and by the absence of information about missing measurements and analysis populations. The record does not report a precision target or a clinically important threshold for the primary measure. The interval therefore quantifies statistical uncertainty under the recalculation, but cannot determine whether the range is clinically meaningful or whether it captures all relevant uncertainty about trial conduct and data availability.

12. 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 planning figures are participants per arm, not total event counts. They are illustrations based on the observed effect, rather than the trial’s original design calculation. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original design assumptions are not reported in the registry record.

The 80% power column gives the planned participants per arm for a hypothetical study designed to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column expresses the corresponding planning target for a 90% chance. These are design concepts: higher target power generally requires more information, and smaller effects require more participants to detect with the same target power.

For the primary outcome, the planning display lists 4 participants per arm for 80% power and 5 participants per arm for 90% power when using 100% of the observed effect. For planning at 75% of the observed effect, the corresponding figures are 6 and 8 participants per arm. For planning at 50% of the observed effect, they are 13 and 17 participants per arm. These are hypothetical planning illustrations, not evidence that the completed trial had those design characteristics or that a particular power was achieved.

The sample-size curve should be read as a visual representation of how the planning requirement changes with the assumed effect size: planning for a smaller fraction of the observed effect requires more participants. These figures are not observed power. They do not establish the probability that the completed trial detected an effect, and they do not replace the trial’s original sample-size rationale, which is not reported in the registry record.

13. 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 = 111.500; pooled standard deviation σ = 50.000.
2. n = 2 × (1.96 + 0.842)² × 50.000² / 111.500² = 3.2, rounded up to 4 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 <- 111.5                      # observed difference in means
sigma <- 50                     # 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(2114307)
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 = 4 (80% power), 5 (90% power)
 75% of observed effect: n per arm = 6 (80% power), 8 (90% power)
 50% of observed effect: n per arm = 13 (80% power), 17 (90% power)
power.t.test: 4.4 
Simulated power at n = 4 per arm: 0.749 (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.

14. Analyses Reported by the Sponsor

The registry’s own primary analysis is a Wilcoxon (Mann-Whitney) comparison of the actual-device and sham-device groups, reported as a superiority analysis with p = 0.001. It does not give an effect estimate or confidence interval for that test. The recalculated result uses the posted group means and standard deviations to estimate a mean difference of 111.5 percentage points, with a 95% confidence interval from 68.68 to 154.3 and an unadjusted p-value of <0.001.

These results are directionally consistent in that both report evidence of a difference favoring a higher mean change in the actual-device group. They are not duplicate calculations of the same analysis: the Wilcoxon method is rank-based, whereas the recalculation concerns the difference between arithmetic means. The recalculated estimate and interval should therefore be read as supplementary quantification of the posted summaries, not as the registry’s own reported effect estimate.

The discrepancy flag is false, so the record does not identify a conflict between the sponsor’s analysis and the recalculation. Even so, the registry’s method and p-value remain the trial’s reported analysis, and the recalculation has the narrower role of describing the unadjusted group-mean contrast. Additional analysis details, including the rationale for selecting the Wilcoxon test and any adjustment procedures, are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and lists secondary outcomes, but does not report a multiplicity adjustment or a hierarchy governing interpretation across outcomes. It also records 3 outcome measures and 4 analyses, without explaining how these measures and analyses were selected or whether all planned analyses are represented. When multiple outcomes or tests are considered, unadjusted p-values do not account for the broader set of opportunities to observe a result. The absence of a reported plan makes it difficult to know how the trial team intended to control or interpret that issue.

The analysis population is not reported in the registry record. The primary outcome summaries list 10.0 participants for the actual-device group and 11.0 for the sham-device group, while the enrollment entry is 22. The record does not explain the relationship between enrollment and the participants contributing to the outcome summaries, including whether any participants lacked measurements or were excluded from analysis. Reasons for missing outcomes, if any, are not reported in the registry record.

The record does not state how missing data were handled, whether the primary analysis followed intention-to-treat principles, or whether sensitivity analyses were performed. These details matter because estimates can be affected when outcome availability is related to participants’ assignment or outcomes. Without such information, readers cannot assess whether the posted summaries represent all randomized participants or a subset with observed measurements.

The registry record also does not report an interim-analysis plan, stopping rules, or the original statistical analysis plan. It does not specify whether outcomes were changed, added, or selectively reported after the study began. These omissions do not prove that any particular practice occurred; they mean that the record does not allow those aspects of the analysis process to be evaluated. The posted results are therefore best interpreted with the reported methods and the limits of the available documentation in view.

16. 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.

For the safety summary, the record lists 11 participants at risk in the actual-device group and 11 in the sham-device group. It reports 0 participants affected by serious adverse events in each group and 0 deaths in each group. The count of participants affected by other adverse events is also 0 in each group, with 11 at risk in each group for that category.

These entries describe what was recorded in the registry safety fields. They do not establish that no symptoms or events of any kind occurred, nor do they establish that the device has no safety risks. The record does not provide a list of non-serious event terms, details about how events were collected, or information about their severity and timing. The serious-event terms list is empty.

The at-risk counts in the safety summary are not the same as a complete account of treatment exposure or follow-up, and the record does not explain how the safety population was defined. Safety counts should therefore be read as registry-reported event summaries, with the limits of their detail and scope in mind.

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

The posted primary summaries show a higher average percentage change in femoral-vein TAMV in the actual-device group than in the sham-device group. The unadjusted recalculation estimates a mean difference of 111.5 percentage points, and its confidence interval is above zero. The registry’s own rank-based analysis also reports statistical evidence of a difference. Together, these findings describe the primary outcome comparison recorded for this trial.

That statistical result is not, by itself, proof of a clinically important benefit. The record does not report a threshold for a meaningful TAMV change, and the primary endpoint is a physiological measurement rather than a direct measure of symptoms or function. The secondary clinical-symptom estimate is uncertain, while numerical results for limb swelling and volume are not reported in the registry record. The results therefore do not establish that the primary measure’s pattern is accompanied by changes across all patient-relevant outcomes.

The findings also do not establish durability beyond the stated 0 and 6 weeks timeframe. The registry record does not report longer follow-up for the primary outcome. It does not provide enough information to determine how missing measurements were handled, who was masked, or whether the observed outcome population corresponds to all randomized participants. Those gaps affect how confidently the result can be generalized.

The trial compares the actual device with a sham device in a small study recorded as enrolling 22 participants. Its results should be understood as evidence from that comparison and the outcomes reported in the registry, not as a general conclusion about all people with venous insufficiency or all possible uses of the device. No medical recommendation follows from these statistical findings alone.

18. Why This Trial Matters Statistically

This trial illustrates why the choice of statistical summary matters. The registry’s primary test is rank-based, while the posted group summaries allow a mean difference to be recalculated. Those methods describe different aspects of a comparison, even when their findings point in a similar direction. Readers benefit from seeing both the registry’s own result and a transparent estimate of the difference between group means, while keeping their distinct interpretations clear.

It also illustrates the difference between evidence against a null model and precision about the size of an effect. The registry reports a p-value for its primary analysis, and the recalculation provides a mean estimate and confidence interval. A p-value alone does not show the magnitude or uncertainty of an effect; an interval alone does not establish clinical importance. Interpreting both helps distinguish statistical evidence from the broader question of what the measured change means.

The contrast between the primary haemodynamic outcome and the less conclusive clinical-symptom result is a reminder that physiological measurements and patient-relevant outcomes answer different questions. The absence of numerical results for limb swelling and volume further shows why complete outcome reporting matters. Without those results, the overall secondary-outcome pattern cannot be evaluated.

Finally, the record shows why reporting the analysis population, missing-data handling, masking details, and multiplicity plan is important. These details help readers assess whether the numerical results match the planned questions and how much confidence to place in them. Their absence does not invalidate the posted results, but it limits the depth of independent statistical interpretation.

19. 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 outcome summaries and the enrollment entry do not correspond to the same reported counts: enrollment is 22, while the outcome summaries list 10.0 participants in the actual-device group and 11.0 in the sham-device group. The record does not explain this difference, identify missing measurements, or state the analysis population. The effect of any unavailable outcomes cannot be assessed from the registry record.

The record labels the trial single-masked but does not identify who was masked or provide details about the sham device. It also does not describe the randomization process or allocation concealment. These omissions limit assessment of possible influences on treatment delivery, participant expectations, and outcome measurement. Because the primary endpoint uses ultrasound, information about measurement procedures and assessor masking would help readers evaluate the risk of bias; such details are not reported in the registry record.

The reported primary analysis is rank-based, but the registry does not provide its effect estimate or confidence interval. The recalculated mean-based estimate is useful for describing the posted averages, but it cannot reproduce a participant-level analysis or account for unreported adjustment and missing-data decisions. The record does not give the original sample-size rationale, a full statistical analysis plan, or an account of multiplicity procedures.

Follow-up for the primary outcome is stated as 0 and 6 weeks. Longer-term outcomes are not reported in the registry record. Although limb swelling, volume, and clinical symptoms are listed as secondary outcomes, numeric results for limb swelling and volume are not reported. These limitations constrain assessment of durability, consistency across outcomes, and the practical meaning of the primary haemodynamic result.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: REVITIVE for the Treatment of Patients With Venous Insufficiency — NCT02114307.
• Registry record last updated 2019-10-10; status last verified 2019-09.
• Results first posted 2019-10-10.
• 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.

23. Record Summary

NCT02114307 is a completed randomized, parallel-group, single-masked trial sponsored by Imperial College London. It compared the REVITIVE IX actual device with a sham device in people with venous insufficiency. The registry lists enrollment of 22 and records the study start as 2014-03-01 and primary completion as 2014-10-01.

The primary outcome was percentage change in femoral-vein time averaged mean velocity, measured by ultrasound from 0 to 6 weeks. The registry reports a Wilcoxon (Mann-Whitney) primary analysis with p = 0.001. An unadjusted recalculation from the posted summaries estimates a mean difference of 111.5 percentage points, with a 95% confidence interval from 68.68 to 154.3.

Clinical symptoms are listed as a secondary outcome; numerical results for limb swelling and volume are not reported in the registry record. Analysis-population details, missing-data handling, multiplicity procedures, the original sample-size rationale, and the identity of the masked party are also not reported in the registry record.