Lymphedema Lower Extremity
Conditions
Keywords
Complex decongestive therapy, Dynamic compression, Non-inferiority trial, Lymphoedema maintenance treatment, Limb volume reduction, Limb volume maintenance
Brief summary
The trial aims to determine whether the dynamic compression device, used in combination with elastic compression garments, is non-inferior to currently available compression devices (CACD) during the maintenance phase of lower-limb lymphoedema treatment. This is a two-arm, parallel-group trial. Both groups will include patients being discharged after the inpatient intensive treatment phase for lower-limb lymphoedema. Eligible participants will be enrolled on the afternoon of their final inpatient treatment day, prior to discharge. Participants will be allocated to one of the following groups: DDS group: elastic compression garment worn at least during the day and as often as possible during the night, according to patient preference and expert advice, plus DDS use for a minimum of 2 hours at the end of the day, used alone without an elastic garment. Control group: elastic compression garment worn at least during the day and as often as possible during the night, according to patient preference and expert advice, plus currently available compression devices, including multicomponent bandages, pneumatic compression devices, and compression wraps, according to patient preference and the center's recommendations. Manual lymphatic drainage will be permitted in both groups. Patients will undergo three assessment visits: Visit 1 / Baseline-Inclusion (V1): afternoon of the final inpatient treatment day, prior to discharge from intensive treatment; Visit 2 (V2): end of week 6, ± 7 days; Visit 3 (V3): end of week 12, ± 7 days.
Detailed description
Background: Lymphedema is a chronic, progressive condition characterized by impaired lymphatic drainage, leading to the accumulation of protein-rich fluid in the interstitial tissues, progressive tissue remodeling, and an increased risk of complications such as infection. Although lymphedema is not curable, standard management combining intensive decongestive therapy followed by lifelong maintenance treatment can significantly reduce limb volume, improve function, and enhance quality of life. However, maintaining long-term disease control remains challenging. The maintenance phase relies primarily on compression therapy and patient self-management. Adherence is often suboptimal due to treatment complexity, cost, limited access to specialized care, and the impact of therapy on daily activities. As a result, patients frequently experience recurrent edema, functional impairment, and infectious complications such as cellulitis, contributing to a substantial clinical and socioeconomic burden. Current standard approaches, including multicomponent bandaging and elastic compression garments, are effective but have important limitations. Multicomponent bandaging is highly operator-dependent, time-consuming, and difficult to maintain because frequent adjustments are required as limb volume changes. Elastic compression garments, while more practical, may be insufficient to achieve sustained decongestion, particularly in patients with moderate-to-severe disease. Overall, existing therapies often fail to provide consistent long-term edema control in real-world settings. Recent technological advances have enabled the development of dynamic compression systems designed to improve usability and treatment consistency. The Dynamic Decongestion System (DDS) is designed to standardize compression delivery, reduce operator dependency, and support patient autonomy in the home setting. This study aims to evaluate the clinical relevance of DDS as an adjunct to standard maintenance therapy in patients with primary or secondary lymphedema who have completed intensive decongestive treatment, with the objective of improving long-term volume control and reducing the overall burden of disease.
Interventions
DEVICEControl group: Currently available compression devices
Participant in the control group may use all currently available compression devices to treat their lymphoedema, in addition to the prescribed elastic garment(s).
Patients in the DDS group are limited to using the DDS device for a minimum of 2h at the end of the day as an adjuvant compression modality to the prescribed elastic garment(s).
Sponsors
Jean-Paul Belgrado
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Prospective, multi-center, interventional, pre-market, pivotal, confirmatory, assessor-blinded study, randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Men and women * Unilateral lower limb lymphedema of stage II or III according to the criteria defined by the International Society of Lymphology * Patients completing an inpatient intensive treatment phase, including patients participating in CIV-25-01-050914, with a minimum of 20% of excess volume reduction * Patients who have given their informed consent freely and signed it prior to any intervention in the study. * Patients with a morphology compatible with the perimetric coverage of the device (calf and thigh). * Patients able to use the device * Patients enrolled in a social security plan or covered by similar health insurance.
Exclusion criteria
* Patients with suspended lymphoedema of the thigh (unaffected calf and foot) * Patients with lipedema * Patients with bilateral lower limb lymphoedema * Patients with a lymphedema associated with active cancer requiring acute chemotherapy, or oncologic relapses, or treatment in progress * Patients with contraindications for compression on the lower limbs such as stent/arterial graft in the area under compression * Peripheral artery disease ABI ≤ 0.6 * Advanced diabetic microangiopathy * Active deep/superficial active or recent venous thrombosis, phlegmasia ceruela dolens (painful blue inflammation), active venous leg ulcers, septic/acute thrombophlebitis of the limb (in the last 6 months) * A condition where increased venous or lymphatic return is undesirable * Neurological disease (including neurogenic diabetic foot, severe peripheral neuropathy of the limb) * Pulmonary embolism (last 6 months), pulmonary edema, poorly controlled asthma * Cardiac insufficiency (compensated or decompensated) * Implantable stimulation devices such as pacemaker * Chronic kidney disease with acute renal failure * Open skin lesions or skin and subcutaneous infection (cellulitis, erysipelas, lymphangitis, etc.) * Skin atrophy of the limb * Bullous dermatoses * Presence of subcutaneous osteosynthesis material with an external component lying subdermally at the level of the treated lower limb * Hyperalgesia of the foot, knee or hip * Patients with a known allergy to the components used in the device * Patients with psychiatric, psychological, or neurological disorders * Patients with impaired cognitive or motor skills and dependent individuals * Patients participating in another clinical trial * Pregnant or breastfeeding women. Women of childbearing potential will undergo Clearblue® urine pregnancy testing prior to enrollment to verify eligibility. * Vulnerable patients, adults being the object of a legal protective measure or unable to express their consent * Patients unable to submit to the constraints of the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative excess limb volume (%) | 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal change in excess volume of the affected limb in ml | 12 weeks | Excess limb volume changes will be measured in ml using three distinct methods: 1. circumferential tape measurements; 2. opto-electric volumetry; 3. 3D scanner. |
| Longitudinal change in the volume of the feet in ml | 12 weeks | assessed by water volumetry (ValGrado method) |
| Dermal and subcutaneous tissue thickness in mm | 12 weeks | assessed by ultrasound imaging |
| Compressibility of the skin and subcutaneous tissue in mm | 12 weeks | assessed by ultrasound imaging under standardized weight |
| Viscoelasticity of the skin and subcutaneous tissue complex | 12 weeks | 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. |
| Skin temperature of the affected limb (in C°) | 12 weeks | based on far infrared thermography mapping |
| Lower limb contour changes | 12 weeks | based on standardized photos and measurements of surface area in cm2 |
| Depth of the pitting sign in mm | 12 weeks | based on standardized measurements |
| Incremental cost-effectiveness ratio (ICER) of DDS versus CATP | 12 weeks | 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 |
| Frequency of infectious episodes | 12 weeks | collected via an ePROM on a weekly basis and by the investigator at V1, V2 and V3, including: * Non-necrotizing dermo-hypodermitis * Lymphangitis |
| Patient-reported quality of life | 12 weeks | 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. |
| Patient's observance to compression therapy | 12 weeks | 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 comfort with compression therapy | 12 weeks | 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 questionnaire (ancillary study) | Ancillary study data will be collected quarterly for a period of up to three years (corresponding to the estimated lifespan of the device) or until CE-marking, whichever occurs first. | 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. |
| Device-specific comfort, ease of use, and satisfaction (trial-specific questionnaire, DDS group) | 12 weeks | 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. |
| Mean total direct medical cost per participant over 12 weeks | 12 weeks | 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) |
| Number of lymphoedema treatment sessions per participant over 12 weeks | 12 weeks | 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 |
| Number and cost of medical devices used per participant over 12 weeks | 12 weeks | 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 |
| Mean out-of-pocket cost per participant over 12 weeks | 12 weeks | 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 |
| Number of lymphoedema-related healthcare consultations and hospitalizations per participant over 12 weeks | 12 weeks | 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 |
Countries
France, Germany
Contacts
CONTACTProf. Jean-Paul Belgrado, PhD
CONTACTVelika V Stoitchkova, MSc
Outcome results
None listed