Assessment of the Efficacy of the Dynamic Decongestive System in the Maintenance Phase of Lower Limb Lymphedema

Change in relative excess limb volume (%) of the affected limb from baseline (Day 0) to the end of the 12-week maintenance phase treatment, based on circumferential tape measurements.

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

assessed by water volumetry (ValGrado method)

assessed by ultrasound imaging

assessed by ultrasound imaging under standardized weight

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.

based on far infrared thermography mapping

based on standardized photos and measurements of surface area in cm2

based on standardized measurements

Cost-effectiveness will be evaluated by calculating the incremental cost-effectiveness ratio (ICER) of DDS versus CATP over 12 weeks. The ICER will be defined as the difference in mean total cost per participant between DDS and CATP, divided by the difference in mean quality-adjusted life-years (QALYs) per participant, with QALYs derived from EQ-5D-5L utility scores collected during the study. A lower ICER (or dominance of one strategy) will indicate a more cost-effective option.

Unit of Measure Cost per QALY gained

collected via an ePROM on a weekly basis and by the investigator at V1, V2 and V3, including:

• Non-necrotizing dermo-hypodermitis
• Lymphangitis

Lymphedema-specific quality of life will be assessed using the Lymphoedema Quality of Life Questionnaire - Leg (LYMQOL-Leg), a validated, limb-specific patient-reported outcome measure for lower-limb lymphedema. The questionnaire includes multiple items covering domains such as function, appearance, symptoms, and mood, each rated on an ordinal scale; domain scores and an overall quality-of-life score are calculated by summing item responses. Scores typically range from a minimum of 1 to a maximum of 4 (or 10 for the global numerical rating scale, depending on the scoring convention used), with higher scores indicating a worse quality of life (greater impairment) in the evaluated domain.

Observance to compression therapy will be assessed using a composite measure based on device-recorded wear time from the investigational compression system and patient-reported use of all compression modalities (DDS device, bandages, garments, and other devices) collected through electronic patient-reported outcome questionnaires and/or patient diaries at week 6 (V2) and week 12 (V3). For each participant, the main adherence metric will be the percentage of prescribed daily wear time (hh:mm) achieved for the investigational device and for any other compression systems, separately for daytime and nighttime use.

Patient-reported comfort with compression therapy will be assessed using the International Compression Club Comfort Questionnaire Patient Version (ICC CQ-P), a validated comfort scale administered in both study groups at week 12. The ICC CQ-P total score is calculated as the sum of item responses, ranging from a minimum of 0 (worst comfort) to a maximum of 10 (best comfort).

Long-term safety and patient experience will be assessed in the ancillary follow-up study using a trial-specific electronic patient-reported outcome questionnaire. The questionnaire evaluates multiple domains related to long-term use of the device, including safety events (e.g., local symptoms or adverse effects), device usage patterns, patient satisfaction, adherence to prescribed use, and perceived device durability. The primary outcome will be a composite safety and usability profile derived from these domains, summarized descriptively over time; worse safety/experience is reflected by higher frequencies of device-related adverse events, lower adherence and satisfaction, and more frequent reports of device problems.

Among participants allocated to the investigational device, device-specific comfort, ease of use, and satisfaction will be assessed at week 12 using a trial-specific patient-reported questionnaire, including a Likert scale, biary responses (Yes/No), and open-ended questions.

Direct medical costs related to lymphoedema management will include costs of treatment modalities (manual lymph drainage, pressotherapy, mechanical devices, medications, skin care), lymphoedema-related healthcare consultations, hospitalizations and diagnostic procedures, and medical devices used during the 12-week period. For each participant, all relevant resource items will be recorded and valued using appropriate unit costs. For each treatment arm, the mean total direct medical cost per participant and standard deviation will be reported.

Unit of Measure Currency units per participant (e.g. EUR per participant)

Use of lymphoedema treatment modalities (manual lymph drainage, pressotherapy, mechanical devices, medications, skin care) will be recorded over 12 weeks, including frequency and duration of each treatment session and location (at home or outside the home). For each treatment arm, the mean number of treatment sessions per participant (by modality) and mean duration per session will be reported.

Unit of Measure Number of sessions per participant

All medical devices used for lymphoedema management during the 12-week period (including DDS or CATP and any additional devices) will be recorded. For each participant, the number of devices used and their associated costs will be documented. For each treatment arm, the mean number of devices per participant and mean device cost per participant will be reported.

Unit of Measure Number of devices per participant and currency units per participan

Out-of-pocket costs borne by participants will include transportation costs (mode of transport, number of journeys, distance between home and hospital, travel time) and co-payments related to lymphoedema care. For each participant, all self-reported out-of-pocket expenses over the 12-week period will be recorded and summed. For each treatment arm, the mean total out-of-pocket cost per participant and standard deviation will be reported.

Unit of Measure Currency units per participant

Lymphoedema-related healthcare professional (HCP) resource use will include consultations with physiotherapists, nurses, lymphoedema specialists and other relevant HCPs, as well as hospitalizations. For each participant, the number of consultations (by HCP category), reasons for consultations, and the number and duration of hospitalizations will be recorded. For each treatment arm, the mean number of consultations and hospitalizations per participant and mean length of stay will be reported.

Unit of Measure Number of events per participant

The safety of the devices used in both groups will be assessed 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), device deficiency (DD), or serious/unexpected serious adverse reaction (S/USAR) during the study. Events will be summarized by category (AE, SAE, ADE, SADE, DD, S/USAR), 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 through their patient diaries.

Unit of Measure Number of participants

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.

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.

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, and (3) 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.