Assessment of the Efficacy of the Dynamic Decongestive System in the Intensive Phase of Lower Limb Lymphedema (EDYDES-int)

Comparador Ativo: Control group: Traditional multicomponent bandages

Control group: Traditional multicomponent bandages Patients in the control group will receive the standard inpatient intensive treatment for lower limb lymphoedema including: compression, manula lymphatci drainage, skin care and exercise

Dispositivo: Control group: Traditional multicomponent bandages

In the control group, patients will wear traditional multicomponent bandages as a compression therapy modality 24/24 during the first 5 days of intensive treatment

Experimental: DDS group: Dynamic compression device (DDS)

DDS group: Dynamic compression device (DDS) Patients in the DDS group will undergo the standard inpatient intensive treatment for lower limb lymphoedema including compression therapy, manual lymphatic drainage, skin care and exercise.

Dispositivo: DDS group: Dynamic compression device (DDS)

Patients in the DDS group will wera the inverventional dynamic compression device as a compression modality 24/24 during the first five days of inpatient intensive treatment.

Relative excess limb volume (%) during intensive treatment

The primary outcome is the relative excess limb volume reduction (percent change) during the first 5 days of intensive treatment. Relative excess volume (%) will be calculated from serial limb volume measurements obtained once or twice daily, according to the number of bandage applications in each center's standard protocol, and expressed as the percentage reduction from baseline. This percentage change will be compared between the two treatment groups, with higher percentage reduction indicating a better decongestive outcome.

Application/removal time (hh/mm)

Time for application of the compression devices measured in minutes at each measurement sessions.

Mean interface pressure amplitude (mmHg) at the skin-bandage interface during standardized maneuvers

The combined mean interface pressure amplitude (mmHg) during the two standardized maneuvers (supine dorsiflexion and standing tiptoeing), measured immediately after each compression system application and prior to its removal during the 5-day intensive treatment, will be calculated for each participant by averaging (with equal weight) the pressure amplitudes from the two maneuvers at each assessment. For each treatment arm (DDS and TMCB), the primary analysis will use the mean of these participant-level composite values across all participants. The primary comparison will test whether this combined mean interface pressure amplitude is higher under DDS than under TMCB, reflecting a superior massage effect.

• H0 : µDDs - µTMBC ≤ 0
• H1 : µDDs - µTMBC > 0

Patient-reported overall satisfaction with the DDS device

Overall satisfaction with the DDS device will be assessed using item 20 of the Patient Satisfaction Questionnaire ("Overall, are you satisfied with the device?"), rated on a 4-point Likert scale (1 = Very unsatisfied, 2 = Unsatisfied, 3 = Satisfied, 4 = Very satisfied). For each treatment arm, the mean score and distribution of responses (number and percentage of participants per category) will be reported. Higher scores indicate greater overall satisfaction with the device.

Outcome Measure Unit of Measure Units on a 4-point Likert scale (1-4)

Longitudinal change in excess volume of the affected limb in ml

Excess limb volume changes will be measured in ml using three distinct methods: 1. circumferential tape measurements; 2. opto-electric volumetry; 3. 3D scanner.

Patient-reported satisfaction with the aesthetics of the DDS device

Satisfaction with the aesthetics of the DDS device will be assessed using item 19 of the Patient Satisfaction Questionnaire ("Overall are you satified with the aesthetics of the device?"), rated on a 4-point Likert scale (1 = Very unsatisfied, 2 = Unsatisfied, 3 = Satisfied, 4 = Versy satisfied). For each treatment arm, the mean score and distribution of responses will be reported. Higher scores indicate greater satisfaction with the aesthetics of the device.

Outcome Measure Unit of Measure Units on a 4-point Likert scale (1-4)

Patient-reported comfort of the DDS device

Comfort of the DDS device will be assessed using item 1 of the Patient Satisfaction Questionnaire ("How do you evaluate the comfort of the device?"), where comfort is rated on a 4-point Likert scale (1 = Very uncomfortable, 2 = Uncomfortable, 3 = Comfortable, 4 = Very comfortable) across several conditions (daytime at rest/in movement, night, calf/thigh, liner). For each participant, a composite comfort score will be calculated as the arithmetic mean of all available item-level ratings (excluding responses marked "NA"). For each treatment arm, the mean composite comfort score and distribution of responses for the overall composite will be reported. Higher scores indicate greater perceived comfort.

Outcome Measure Unit of Measure Units on a 4-point Likert scale (1-4)

Patient-reported usability of the DDS device

Usability of the DDS device will be assessed using items 8, 9, 10, 11 and 12 of the Patient Satisfaction Questionnaire (intuitiveness of application, clarity of instructions for use and maintenance, clarity of contraindications and warnings, and ease of using key device functions). Individual questions are rated on 4-point Likert scales (e.g. Very easy- Very difficult, Very clear - Unclear). Response options will be coded so that higher values reflect better usability (e.g. 1 = Very difficult / unclear up to 4 = Very easy / very clear). For each participant, a composite usability score will be calculated as the arithmetic mean of all coded items with non-missing responses. For each treatment arm, the mean composite usability score and distribution of composite scores will be reported. Higher scores indicate better perceived usability.

Outcome Measure Unit of Measure Units on a 4-point Likert scale (1-4)

Number of participants intending to continue use of the DDS device after the clinical study

Intention to continue using the DDS device will be assessed using item 21 of the Patient Satisfaction Questionnaire ("Outside of the clinical trial, do you plan to continue wearing the device: During the intensive phase? During the maintenance phase?"), each with Yes/No response options. The primary reported value will be the number and percentage of participants who answer "Yes" for continued use during the maintenance phase. Numbers and percentages for the intensive phase will be reported descriptively.

Outcome Measure Unit of Measure Number of participants

Number of participants with adverse events and device-related safety issues

The safety of the DDS and TMCB devices will be evaluated by counting the number of participants who experience at least one adverse event (AE), serious adverse event (SAE), adverse device effect (ADE), serious adverse device effect (SADE), or device deficiency (DD) during the study, as well as the total number of events in each category. Events will be summarized by type (AE, SAE, ADE, SADE, DD), severity, and relationship to the investigational device for each treatment arm. All untoward events will be collected by investigators during the intervention and follow-up periods and by participants via patient diaries.

Unit of Measure Number of participant

Exploratory outcomes: Longitudinal change in excess volume of the affected limb in ml

Excess volume in the affected limb will be measured in ml during the first 2 hours, 3 days, and 5 days of intensive using tow distinct methods: 1. opto-electric volumetry; 2. 3D scanner.

Exploratory outcome: Longitudinal change in foot volume of the affected limb in ml

Foot volume will be measured in ml at 2h, 3 days and 5 days of the intensive treatment phase using the ValGrado water displacement method.

Exploratory outcome: Lower limb contour area (cm2)

Lower limb contour changes based on standardized photos taken at baseline and Day 5 in cm and cm2.

Exploratory outcome: Change in skin temperature by infrared thermography (degrees Celcius)

This exploratory outcome will assess the change in skin temperature between baseline and the end of the 5-day intensive treatment using skin infrared thermography. Temperature will be measured in degrees Celsius (°C) at predefined regions of interest on the affected limb. The main metric will be the absolute change in skin temperature (end of treatment minus baseline) for each region; higher positive or negative changes indicate greater deviation from baseline.

Exploratory outcome: Viscoelasticity of the skin and subcutaneous tissue complex

Viscoelasticity of the skin and subcutaneous tissue will be assessed using a handheld, non-invasive myotonometer (Myoton PRO). The device delivers a brief, low-force mechanical impulse through a probe placed on the skin and records the resulting damped oscillation of the underlying tissues, from which a quantitative viscoelasticity index is derived.

Exploratory outcome: Pitting sign depth

Depth of the pitting sign in mm recorded at each measurement session

Exploratory outcome: Change in dermal microcirculatory response by capillaroscopic imaging

This exploratory outcome will assess the change in dermal microcirculatory response between baseline and the end of the 5-day intensive treatment using capillaroscopic imaging. The dynamic response of skin capillaries will be quantified primarily by changes in red pixel intensity on standardized images acquired at predefined regions of interest. Higher or lower red pixel intensity at day 5 compared with baseline will indicate a change in capillary perfusion.

Exploratory outcome: Weight of the compression system at each measurement session (kg)

Outcome Measure Description The weight of the applied compression system (DDS or TMCB) will be measured at each scheduled measurement session using a calibrated scale. For each treatment arm and time point, the mean weight and standard deviation will be reported.

Exploratory outcome: Change in step length while wearing compression bandaging

Step length (meters) will be measured during standardized walking trials at baseline (before intensive compression) and at the end of the 5-day intensive treatment while wearing compression bandaging. For each participant, change from baseline in step length will be calculated. For each treatment arm, mean change and standard deviation will be reported. A positive or negative change indicates an effect of compression bandaging on step length.

Unit of Measure Meters

Exploratory outcome: Healthcare professional-reported satisfaction with the aesthetics of the DDS device

Satisfaction with the aesthetics of the DDS device will be assessed using the item "Overall, are you satisfied with the aesthetics of the device?" from the HCP Satisfaction Questionnaire, rated on a 4-point Likert scale (1 = Very unsatisfied, 2 = Unsatisfied, 3 = Satisfied, 4 = Very satisfied). For all healthcare professionals who complete the questionnaire, the mean score and distribution of responses (number and percentage in each category) will be reported. Higher scores indicate greater satisfaction with the aesthetics of the device.

The questionnaire will be completed once at the end of the trial. Unit of Measure Units on a 4-point Likert scale (1-4)

Exploratory outcome: Assess the coherence between three volumetric methods

This exploratory outcome will assess the coherence between different tools used to quantify limb volume in lymphedema. The analysis will compare volume measurements obtained from a 3D scanner (EinStar VEGA), circumferential tape measurements, and a Perometer to evaluate the degree of correlation and agreement between these methods.

Exploratory outcome: To assess the coherence between data registered by the DDS integrated sensor system and clinical measurements.

This exploratory outcome will assess the coherence between data recorded by the integrated sensor system of the investigational compression device and selected clinical and patient-reported measures. The analysis will compare device-recorded signals with (1) tissue stiffness values obtained using a handheld myotonometer (MyotonPro), (2) limb volume estimates derived from circumferential tape measurements, (3) patient's activity based on ActiGraph data, and (4) weekly questionnaire responses in the adherence/observance domain. Coherence will be examined using correlation and agreement analyses to determine how closely sensor-derived data reflect these external measures.

Number of participants intending to continue long-term use of DDS device

Intention to continue long-term use of the DDS calf device, thigh device and liner will be assessed via ancillary questionnaire items "Do you plan to continue using the following devices?" with Yes/No responses for calf, thigh and liner. At each 3-month assessment, the number and percentage of participants who answer "Yes" for each component will be reported. Reasons for discontinuation (open-ended) will be summarized descriptively.

Unit of Measure Number of participants

Exploratory outcome: Change is skin and subcutaneous tissue thickness by ultrasound (mm)

This exploratory outcome will assess the change in skin and subcutaneous tissue thickness between baseline and the end of the 5-day intensive treatment using B-mode ultrasound imaging. Thickness will be measured in millimeters (mm) at predefined regions of interest on the affected limb. The main metric will be the absolute change in tissue thickness (end of treatment minus baseline), with negative values indicating a reduction in thickness.

Exploratory outcome: Change in skin and subcutaneous tissue thickness under standardized compression by ultrasound (mm)

This exploratory outcome will evaluate how skin and subcutaneous tissue thickness changes under controlled mechanical loading between baseline and the end of the 5-day intensive treatment. Using ultrasound imaging, tissue thickness (mm) will be recorded at predefined regions of interest while applying three progressively increasing standardized pressure levels (in Pascal, Pa). The main metric will be the change in thickness under each pressure level (end of treatment minus baseline), allowing characterization of treatment-related changes in tissue response to compression.

Exploratory outcome: Change in veno-arteriolar reflex by standard imaging

This exploratory outcome will assess the change in the veno-arteriolar reflex (VAR) between baseline and the end of the 5-day intensive treatment using standardized photographic or video imaging. The VAR will be evaluated qualitatively by visual assessment of skin color and perfusion changes in response to postural or positional maneuvers. Changes in the qualitative VAR assessment from baseline to day 5 will indicate modification of the local microvascular regulatory response.

Exploratory outcome: Exploratory coherence between methods of assessing skin and subcutaneous tissue thickness

This exploratory outcome will assess the coherence between different modalities used to evaluate skin and subcutaneous tissue thickness (mm). The analysis will compare measurements obtained from ultrasonography, compressibility assessment, and the pitting test to determine the degree of correlation and agreement between these methods

Exploratory outcome: Change in cadence while wearing compression bandaging

Cadence (steps per minute) will be measured during standardized walking trials at baseline and at the end of the 5-day intensive treatment while wearing compression bandaging. For each participant, change from baseline in cadence will be calculated. For each treatment arm, mean change and standard deviation will be reported. Changes in cadence indicate an effect of compression bandaging on gait rhythm.

Unit of Measure Steps per minute

Exploratory outcome: Change in stance time while wearing compression bandaging

Stance time (seconds per step) will be measured during standardized walking trials (30 m walking distance) at baseline and at the end of the 5-day intensive treatment while wearing compression bandaging. For each participant, change from baseline in stance time will be calculated. For each treatment arm, mean change and standard deviation will be reported. Variations in stance time reflect changes in loading and stability under compression bandaging.

Unit of Measure Seconds (or percentage of gait cycle - choose one and keep it consistent)

Exploratory outcomes: Change in peak plantar pressure while wearing compression bandaging

Peak plantar pressure (kPa) will be recorded during standardized walking trials at baseline and at the end of the 5-day intensive treatment while wearing compression bandaging. For each participant, change from baseline in peak plantar pressure will be calculated. For each treatment arm, mean change and standard deviation will be reported. Changes in plantar pressure profiles indicate modifications in load distribution under compression bandaging.

Unit of Measure kPa

Exploratory outcome: Healthcare professional-reported satisfaction with the perceived efficacy of the DDS device

Satisfaction with the perceived efficacy of the DDS device will be assessed using the item "Overall, are you satisfied with the effectiveness of the device?", rated on a 4-point Likert scale (1 = Very unsatisfied, 2 = Unsatisfied, 3 = Satisfied, 4 = Very satisfied). The mean score and distribution of responses will be reported. Higher scores indicate greater satisfaction with the perceived efficacy of the device.

The questionnaire will be completed once at the end of the study. Unit of Measure Units on a 4-point Likert scale (1-4)

Exploratory outcome: Healthcare professional-reported usability of the DDS device for application and removal

Usability of the DDS device for application and removal will be assessed using the Likert-scale items on ease of donning and doffing the device for calf, thigh and liner ("How do you assess the application/removal of the device ?"), each rated on a 5-point scale (Very easy, Easy, Difficult, Very difficult, N/A). Responses will be coded from 1 to 4 so that higher values indicate greater ease of use (1 = Very difficult, 4 = Very easy; N/A treated as missing). For each healthcare professional, a composite usability score will be calculated as the arithmetic mean of all non-missing items related to application and removal. The mean composite score and distribution of composite scores will be reported. Higher scores indicate better perceived usability.

The questionnaire will be completed once at the end of the trial. Unit of Measure Units on a 4-point Likert scale (1-4

Exploratory outcome: Healthcare professional-reported ease of using the DDS control unit

Ease of using the DDS control unit will be assessed from the items on using the control box, on/off switch, switching between "Night" and "Day" programs, understanding battery-status colours, and recharging the battery. Each item is rated on a 5-point scale (Very easy, Easy, Difficult, Very difficult, N/A). Responses will be coded from 1 to 4 so that higher values indicate greater ease of use (1 = Very difficult, 4 = Very easy; N/A treated as missing). For each healthcare professional, a composite control-unit usability score will be calculated as the arithmetic mean of these items. The mean composite score and distribution of composite scores will be reported. Higher scores indicate better perceived usability of the control unit.

The questionnaire will be completed once at the end of the trial. Unit of Measure Units on a 4-point Likert scale (1-4)

Exploratory outcome: Healthcare professional-reported clarity of DDS instructions and safety information

Clarity of the DDS documentation will be assessed using three items on the clarity of instructions for use, maintenance instructions, and contraindications/warnings, each rated on a 4-point scale (Very clear, Clear, Not very clear, Not clear). Responses will be coded from 1 to 4 so that higher values indicate greater clarity (1 = Not clear, 4 = Very clear). For each healthcare professional, a composite documentation-clarity score will be calculated as the arithmetic mean of the three coded items. The mean composite score and distribution of composite scores will be reported. Higher scores indicate clearer perceived documentation.

The questionnaire will be completed once at the end of the study. Unit of Measure Units on a 4-point Likert scale (1-4)

Exploratory outcome: Number of healthcare professionals who perceive the DDS device as differentiating from currently available products

Perceived differentiation of DDS versus currently available products will be assessed using the item "Do you think the DDS system offers a unique solution compared to the products currently available on the market?" with four response options ("Strongly agree," "Somewhat agree," "Somewhat disagree," "Strongly disagree").Responses will be coded from 1 to 4 so that higher values indicate higher levels of agreement (1 = Strongly disagree, 4 = Strongly agree). For each healthcare professional, a composite agreement score will be calculated as the arithmetic mean of all non-missing items. The mean composite score and distribution of composite scores will be reported. Higher scores indicate better perceived differentiation vs exsting products.

The questionnaire will be completed once at the end of the trial. Unit of Measure Number of healthcare professionals

Exploratory outcome: Number of healthcare professionals intending to prescribe the DDS device after the study

Intention to prescribe the DDS device after the clinical study will be assessed using the item "Outside of the clinical trial, would you prescribe the DDS device?" with separate Yes/No questions for the intensive phase and maintenance phase. Numbers and percentages for "Yes" in the intensive phase will be reported descriptively.

The questionnaire will be completed once at the end of the trial. Unit of Measure Number of healthcare professionals

Number of participants with device-related adverse events during long-term use of DDS

Device-related adverse events during long-term use of DDS (e.g., pain, skin irritation, redness, feeling of excessive compression, excessive sweating, numbness and other reported symptoms) will be collected via the ancillary electronic questionnaire administered every 3 months. At each time point, the number and percentage of participants who report at least one adverse event they consider related to the DDS device or liner will be recorded, together with severity (mild, moderate, severe), body location (calf, thigh, liner), and consequence (e.g., reduction in wear time, temporary discontinuation, permanent discontinuation, medical consultation, no change).

Unit of Measure Number of participants

Average weekly frequency of DDS use during long-term follow-up

Adherence to DDS use will be assessed via the ancillary questionnaire item "How frequently do you use the device ?" (number of days per week) and "On average , how many hours per day do you wear the device ?" (hours per day). For each participant and each 3-month assessment, the frequency of use will be described as the number of days per week and hours per day reported. For each time point, the mean number of days per week and mean hours per day (and standard deviations) will be reported across participants.

Unit of Measure Days per week and hours per day

Number of participants reporting DDS device deterioration or malfunction during long-term use

Device deterioration and malfunctions will be assessed via ancillary questionnaire items on the condition of the calf, thigh and liner components (no change, slight deterioration, significant deterioration of textile, exterior, hook-and-loop fasteners, control unit) and on observed functional defects ("Have you noticed any malfunctioning of the DDS device?"). At each 3-month assessment, the number and percentage of participants reporting any deterioration (slight or significant) and/or at least one device malfunction will be recorded.

Unit of Measure Number of participants

Number of participants reporting perceived clinical and practical benefits of long-term DDS use

Perceived benefits of DDS will be assessed via the ancillary questionnaire checklist (e.g., decreased limb volume, reduced heaviness and tension, decreased pain, improved skin suppleness, improved mobility, facilitation of daily activities, improved autonomy, improved adherence to treatment, reduced need for manual lymph drainage, improved sleep, improved quality of life, better tolerance of other compression devices). At each 3-month assessment, for each listed benefit, the number and percentage of participants who select that benefit will be reported.

Unit of Measure Number of participants

Participant-reported satisfaction with DDS calf, thigh and liner components during long-term use

Satisfaction with the calf, thigh and liner components of the DDS device will be assessed using the ancillary questionnaire items "Overall, are you satisfied with the following measures?" with a 4-point Likert scale (Very satisfied, Satisfied, Somewhat dissatisfied, Dissatisfied) for the calf device, thigh device and liner. At each 3-month assessment, for each component, the distribution of responses and mean satisfaction score (coded 1-4, where higher scores indicate greater satisfaction) will be reported.

Unit of Measure Units on a 4-point Likert scale (1-4)