Blood Flow Stimulation in the Lower Limbs by Application of Different External Devices: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Blood Flow Stimulation in the Lower Limbs by Application of Different External Devices (NCT03420625), a non-randomized na study. The primary outcome is Blood Flow - Peak Systolic Velocity (cm/Sec).

2. Clinical Question

The study examined whether four devices produced different haemodynamic effects in the lower limbs of healthy participants. The primary measure was peak systolic velocity in the popliteal vein, assessed using Doppler ultrasound. The registry record describes sequential use of the devices and a comparison of their effects, but does not report the numerical outcome results or an analysis comparing devices.

3. Trial Design

This completed study was registered as NCT03420625, with the title “Blood Flow Stimulation in the Lower Limbs by Application of Different External Devices.” It was sponsored by Karolinska University Hospital. The registry lists the phase as NA, allocation as nonrandomized, masking as none, and the model as crossover. Enrollment was 10. The listed study dates are 2016-09 for the start and 2017-01 for primary completion.

Participants were healthy persons, and the four device interventions were performed sequentially on each participant after baseline. The devices were Foot IPC, Rapid calf IPC, Slow calf IPC, and Calf NMES. One participant did not perform Rapid calf IPC, so the primary-outcome population description records that intervention as performed by 9 participants; the other interventions are described as performed by 10. The record does not report the reason for the missed intervention.

In general, a crossover design measures more than one intervention in the same participant. This can make within-participant comparisons informative because each person contributes measurements under multiple conditions. It also means that sequence and timing can matter. The record says the interventions were sequential and lists them after baseline, but does not report randomized order, a washout period, or an assessment of period or carryover effects. These details are not reported in the registry record.

The registry lists Venous Stasis and Deep Vein Thrombosis as conditions, while its study description identifies the participants as healthy. It does not report that participants were enrolled as patients with either condition. The study is not described as a randomized treatment comparison or as a clinical-outcome trial.

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

Analysis population for the primary outcome, as defined in the registry: The interventions were performed sequentially on each participant as listed after baseline, in total 10 participants. One patient did not perform the Rapid calf IPC intervention

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 Blood Flow - Peak Systolic Velocity (cm/Sec), measured over up to one hour in total.

The primary endpoint was blood-flow peak systolic velocity, recorded in cm/s. It was assessed in the popliteal vein with Doppler ultrasound, with a timeframe of up to one hour in total. The registry specifies that the outcome is a mean with standard deviation as its dispersion measure. Numerical means and standard deviations are not reported in the registry record.

In general, peak systolic velocity describes the highest measured speed of blood flow during the systolic part of a cardiac cycle. Doppler ultrasound uses changes in reflected sound waves to estimate blood-flow velocity. Measuring this quantity allows investigators to describe an immediate haemodynamic response to an intervention. It is a physiological measurement, not by itself a measure of a clinical event or a patient’s longer-term health.

The choice of a continuous velocity measure permits description of both the average measured response and its variation among participants. In general, a mean conveys the central level of a continuous measurement, while a standard deviation describes how spread out individual measurements are around that mean. Neither statistic alone shows the precision of a comparison between devices. That would require estimates of the relevant differences and their uncertainty, which are not reported in the registry record.

The registry also lists tolerability to IPC and NMES according to a visual analogue scale from 0-10 as a secondary outcome. Its numerical results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Design and comparison. The study is recorded as nonrandomized and crossover, with no masking. Participants received the devices sequentially after baseline, according to the registry description. In general, a crossover design obtains measurements from the same participant under multiple interventions. This can support comparisons that use each participant as their own reference, reducing the effect of stable personal characteristics on those comparisons. However, interpretation depends on how the sequence was arranged and whether one intervention could influence measurements taken later. The registry record does not report randomized sequence, washout procedures, or analyses of order and carryover.

Because allocation was nonrandomized, the device conditions should not be treated as independent randomized arms. The registry itself identifies the comparison as nonrandomized. In general, random allocation helps balance known and unknown influences between groups; without it, differences associated with sequence, timing, or other factors can be difficult to separate from differences associated with the device. In a crossover, paired participant-level measurements may help address some between-person variation, but the necessary paired analysis and its results are not reported in the registry record.

Outcome scale and summaries. The primary endpoint is a continuous measure: peak systolic velocity in the popliteal vein, in cm/s, measured with Doppler ultrasound. The registry specifies a mean and standard deviation. In general, the mean summarizes the central value of continuous observations, and the standard deviation describes their spread. A standard deviation is not the uncertainty of the mean or of a difference between interventions. For uncertainty about an estimated mean or contrast, an analysis would ordinarily report a standard error or confidence interval. Such numerical estimates are not reported in the registry record.

The record describes the measurement period as up to one hour in total. It does not describe the number or timing of readings within that period, how repeated readings were combined, or any quality-control rules for the ultrasound measurements. These measurement and analysis details are not reported in the registry record. Their absence means that a reader cannot reconstruct how any participant-level endpoint value would have been formed.

Within-participant inference. In general, an analysis for crossover data should reflect that repeated measurements from one participant are related. Treating them as unrelated observations can misrepresent the uncertainty in a device comparison. A paired contrast, or a model that accounts for participant-level clustering and relevant sequence or period terms, can represent this dependence; the choice depends on the design and data. The registry record does not report an analysis method, model specification, estimated contrasts, confidence intervals, or p-values. No particular model should therefore be attributed to the study.

A confidence interval is a range of values compatible with the data and the assumptions of a statistical procedure. Its width is informative about precision, while its location helps show the direction and scale of an estimate. In general, an interval should be interpreted alongside the endpoint’s units and the design, not as a guarantee that the true value lies in the interval. The registry record does not report confidence intervals for the primary outcome or any device comparison.

A p-value is calculated relative to a null hypothesis and a statistical model. In general, a small p-value is not a measure of effect size, probability that the null hypothesis is true, or evidence of clinical importance. Interpretation requires the estimate, its uncertainty, the planned question, and the quality of the analysis. No p-value or inferential analysis for the primary endpoint is reported in the registry record, so no significance claim can be evaluated.

Variation and distribution. A mean and standard deviation are most directly informative when the distribution is not strongly distorted by unusual values or marked asymmetry. In general, individual data or distributional summaries help assess whether a mean adequately describes the observations. The registry record does not report participant-level data, distributions, or diagnostic checks. It is therefore not possible to assess the shape of the measurements or the influence of outlying values.

Over-dispersion is a general concern when observed variation is greater than a statistical model assumes. For a continuous outcome, a model that understates variation can make uncertainty appear smaller than it is. The record does not report a model or variance diagnostics, so there is no basis to say whether over-dispersion was relevant or how it was handled. This is a general methodological consideration, not a reported feature of this study.

Planning and power. In general, a sample-size calculation uses assumptions about the target effect, variability, significance level, power, and allocation or design structure. For a crossover study, assumptions should reflect within-participant variation and the planned comparison. A planning calculation is not a result and cannot demonstrate that an observed effect is real. Any sample-size illustrations based on an observed effect are planning illustrations, not observed power. The registry record does not report a sample-size justification or the assumptions used to plan enrollment.

Multiplicity. The registry lists five outcome measures and four device modalities. In general, testing multiple outcomes or multiple pairwise comparisons creates multiple opportunities for a nominally unusual result. A prespecified hierarchy or multiplicity adjustment can help control the interpretation of a family of tests. The registry record does not report a statistical analysis plan, a testing hierarchy, or a multiplicity method. Since no analyses are reported, it is not possible to determine how multiplicity was handled.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Baseline", "Foot IPC", "Rapid Calf IPC", "Slow Calf IPC", "Calf NMES")
n   <- c(10, 10, 9, 10, 10)
m   <- c(14.1, 29.5, 161.6, 39, 42.1)
sp  <- c(3.42, 8.4, 47.8, 12.5, 14.9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Baseline  10  14.100  3.420  11.653  16.547
CARM  Foot IPC  10  29.500  8.400  23.491  35.509
CARM  Rapid Calf IPC  9  161.600  47.800  124.858  198.342
CARM  Slow Calf IPC  10  39.000  12.500  30.058  47.942
CARM  Calf NMES  10  42.100  14.900  31.441  52.759

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including the primary blood-flow endpoint and a secondary tolerability outcome. It does not report a statistical analysis plan, a hierarchy for testing outcomes, or a method for adjusting for multiple comparisons. With four device conditions, several pairwise comparisons could be of interest, but the registry record does not state which contrasts were planned or how they would be interpreted. No analyses are reported, so the effect of multiplicity on any inferential claims cannot be assessed.

The population description states that one participant did not perform Rapid calf IPC. The corresponding at-risk count in the adverse-event record is 9 for Rapid calf IPC, compared with 10 for the other devices. The registry does not report why the participant missed that intervention, whether any primary-outcome measurements were otherwise missing, or how missing measurements were handled. It does not describe imputation, a complete-case approach, or sensitivity analyses; these details are not reported in the registry record.

The registry identifies 10 enrolled participants but does not define an analysis population, such as an intention-to-treat or per-protocol population. In general, an analysis population describes which participants and observations contribute to a particular estimate. In crossover work, decisions about incomplete sequences can affect which within-participant comparisons are available. Without a reported population definition and analysis method, the reader cannot determine the analytic denominator for primary outcome comparisons beyond the intervention participation counts described in the record.

The registry does not report interim analyses, a sample-size justification, or a prespecified strategy for handling missing data and multiple testing. These omissions do not establish that such procedures were or were not used; they mean those details are not reported in the registry record.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists no serious adverse events for any of the four device conditions and no deaths. The number at risk is 10 for Foot IPC, Slow calf IPC, and Calf NMES, and 9 for Rapid Calf IPC. These are the registry’s counts, not estimates of risk in a broader population.

The record lists 7 participants with events in the other adverse-event category for Calf NMES, with 10 at risk. It lists 0 participants with such events for Foot IPC, Rapid Calf IPC, and Slow Calf IPC. No serious adverse-event terms are listed. The record does not describe the nature, severity, timing, or attribution of the other events, so their clinical character cannot be determined from these counts.

In general, an adverse-event count records events within the registry’s specified category and observation period; it does not by itself establish that a device caused an event. A zero serious-event count means none were recorded in that category in this study, not that serious events are impossible. Because enrollment was 10 and one participant did not undergo Rapid calf IPC, the counts should be read as study-specific observations, not as precise estimates of how often events occur outside the study. The registry record does not report further safety analyses.

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

The record describes a physiological study of four devices in 10 healthy participants. It specifies a primary endpoint—peak systolic velocity in the popliteal vein—and identifies Doppler ultrasound as the measurement method. The interventions were performed sequentially after baseline in a nonrandomized crossover design. These details define the question and the way measurements were gathered, but they do not answer which device produced the greatest measured velocity response.

Numerical primary-outcome values, device contrasts, measures of uncertainty, and inferential analyses are not reported in the registry record. As a result, the posted information does not establish the size, precision, or statistical significance of differences among devices. It also does not establish whether observed responses were consistent across participants. A study’s enrollment count and design description cannot substitute for outcome estimates.

The endpoint is a measure of blood-flow velocity, not a direct measure of prevention of venous stasis or deep vein thrombosis, and the record describes the participants as healthy. The registry’s listing of Venous Stasis and Deep Vein Thrombosis as conditions should not be taken to mean that the enrolled participants had those conditions. The record does not report clinical outcomes that would show whether any device changed disease occurrence or patient health.

The adverse-event record reports no serious adverse events or deaths, and it records 7 participants with other adverse events during Calf NMES. These are descriptive registry counts. They do not prove that an intervention is safe or unsafe, and the record does not give enough information about the other events to characterize them further.

In general, physiological measurements can help characterize immediate responses under study conditions. Whether such measurements predict outcomes in other populations or settings requires evidence beyond the measurements reported in this registry record. No treatment recommendation or conclusion about comparative clinical benefit follows from the available information.

14. Why This Trial Matters Statistically

Statistically, this study is notable for its within-participant crossover structure: the same participants were intended to undergo multiple device conditions. In general, that design can make comparisons less dependent on stable differences between people, because each participant can contribute measurements under different conditions. It also requires analysis that recognizes that measurements from the same person are related. The registry identifies the design but does not report an analysis of the primary endpoint.

The study’s primary measurement is continuous, and the record specifies a mean with standard deviation. This makes it important to distinguish descriptive summaries from comparative inference. Means and standard deviations describe the observed measurements, while a comparison requires an estimate of the contrast and its uncertainty. Those numerical results are not reported in the registry record.

The nonrandomized allocation and sequential intervention order are also important statistical features. In general, if order or timing is associated with the measured response, a device contrast may reflect more than the device condition itself. The record does not report whether order was randomized or whether period effects were assessed. This illustrates why a design label alone is not enough to determine how well a comparison separates intervention effects from other influences.

Finally, the small enrolled cohort and the incomplete Rapid calf IPC participation make clarity about analysis populations and missing data especially relevant. The record documents the incomplete intervention but does not report how it was addressed in primary-outcome analyses. The registry therefore offers a useful example of why outcome estimates, uncertainty, and analysis details are necessary for statistical interpretation, not just a description of enrollment and procedures.

15. 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 most immediate limitation of the registry record is that it does not report numerical results for the primary endpoint. Means, standard deviations, comparisons, confidence intervals, and p-values are not reported in the registry record. This prevents assessment of the observed response, its variability, and the precision of any contrast among devices.

The study enrolled 10 healthy participants, and one participant did not perform Rapid calf IPC. The record does not explain why that intervention was missed or describe how incomplete participation affected the primary analysis. It also does not report participant-level measurements or an analysis population. The reader cannot determine from the record whether the same set of participants contributed to every device comparison.

The nonrandomized, unmasked, sequential crossover design limits what can be inferred about comparative effects. In general, sequential measurements can be affected by order or timing, and lack of masking can influence measurement or reporting. These are design considerations, not evidence that bias occurred. The record does not report randomized order, washout details, or analyses of sequence and carryover, so those aspects cannot be evaluated.

The endpoint is an ultrasound measurement of peak systolic velocity, with a stated timeframe of up to one hour in total. The record does not provide details about repeated measurement timing, how readings were combined, or measurement reliability. It also does not report results for the secondary tolerability outcome.

The registry lists Venous Stasis and Deep Vein Thrombosis as conditions but describes the participants as healthy. It does not report clinical outcomes or a patient population with either condition. Therefore, the described physiological study does not establish how the measured responses relate to clinical outcomes or to people with those conditions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Blood Flow Stimulation in the Lower Limbs by Application of Different External Devices — NCT03420625.
• Registry record last updated 2020-09-23; status last verified 2020-09.
• Results first posted 2019-02-12.
• 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.

19. Record Summary

NCT03420625 is a completed, nonrandomized, unmasked crossover study sponsored by Karolinska University Hospital. Enrollment was 10, and the registry lists the start as 2016-09 and primary completion as 2017-01. Ten healthy participants were intended to undergo four sequential device interventions after baseline; one participant did not perform Rapid calf IPC.

The primary outcome was peak systolic velocity in the popliteal vein, measured by Doppler ultrasound and specified as a mean with standard deviation. The registry also lists tolerability according to a visual analogue scale from 0-10 as a secondary outcome. Numerical primary and secondary outcome results, statistical analyses, and a sample-size justification are not reported in the registry record.

The adverse-event record lists no serious adverse events and no deaths. It records 7 participants with other adverse events for Calf NMES and 0 for the other device conditions. No serious-event terms are listed. These counts are descriptive and do not establish comparative safety.