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

A Multicenter Controlled Randomised Clinical Trial to Assess the Efficacy of the Dynamic Decongestive System During the Maintenance Phase of Lower Limb Lymphedema Treatment

The trial aims to compare the dynamic compression device in combination with elastic compression garments is non-inferior to all currently available compression devices (CACD) during the maintenance phase of lower limb lymphoedema treatment.

The trial involves 2 parallel groups. Both groups will include patients who are being discharged from the inpatient intensive treatment phase for lower limb lymphoedema. Eligible participants will be enrolled in the study on the afternoon of their last inpatient treatment day, prior to discharge.

DDS group: elastic compression garment at least during the day and as often as possible during the night (depending on personal preferences and expert advice) + DDS for a minimum of 2h at the end of the day (alone without an elastic garment).

Control group: elastic compression garment at least during the day and as often as possible during the night (depending on personal preferences and expert advice) + all currently available compression devices (CACD), including multicomponent bandages, pneumatic compression devices, and compression wraps, depending on patient preference and the center's recommendations.

Manual lymphatic drainage will be acceptable for both groups.

Patients will be assessed during three measurement sessions:

Visit 1 / baseline-inclusion (V1) - on the afternoon of their last inpatient treatment day, prior to discharge from intensive treatment, Visit 2 (V2) - at the end of week 6 (± 7 days) Visit 3 (V3) - at the end of week 12 (± 7 days)

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphedema Lower Extremity
• Intervention / Treatment: Device: Control group: Currently available compression devices; Device: DDS group: Dynamic compression device (DDS)

Detailed Description

Background Lymphedema is a chronic, progressive condition characterized by impaired lymphatic drainage leading to accumulation of protein-rich fluid in the interstitial tissues, progressive tissue remodeling, and increased risk of complications such as infection. Although incurable, standard management combining intensive decongestive therapy followed by lifelong maintenance can significantly reduce limb volume, improve function, and enhance quality of life. However, 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 impact on daily activities. As a result, patients frequently experience recurrence of edema, functional impairment, and infectious complications such as cellulitis, contributing to substantial clinical and socioeconomic burden.

Current standard approaches, including multi-component bandaging and elastic compression garments, are effective but have important limitations. Multi-component bandages are highly operator-dependent, time-consuming, and difficult to maintain due to the need for frequent adjustment as limb volume changes. Compression garments, while more practical, may be insufficient for sustained decongestion, particularly in 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 an innovative device incorporating embedded micromotors to automatically adjust bandage tension in response to limb volume changes, maintaining a predefined pressure gradient required for effective lymphatic drainage. This approach aims to standardize compression delivery, reduce operator dependency, and support patient autonomy in the home setting.

This study aims to evaluate the clinical relevance of the DDS as an adjunct to standard maintenance therapy in patients with primary or secondary lymphedema who have completed intensive decongestive treatment, with the goal of improving long-term volume control and reducing disease burden.

Description of the investigational medical device The investigational device is a wearable, motor-driven compression orthosis intended to provide adjustable external pressure to the lower limb in order to reduce or maintain edema volume in patients with primary or secondary lymphedema during the maintenance phase of treatment. It is designed for home and clinical use under medical supervision and is not yet commercially approved or CE marked.

Device overview and use The device applies static and dynamic compression over the lower leg and/or thigh through multiple circumferential segments that can be individually tightened and released under the control of an integrated control unit. It offers two preset operating programs (a higher-pressure, shorter-duration "day" mode and a lower-pressure, longer-duration "night" mode) within a pressure range consistent with published recommendations for compression therapy in lymphedema. A simple user interface (on/off button, day/night selector, indicator light) and use over a non compressive liner are intended to facilitate safe application by trained patients, caregivers, or healthcare professionals.

Mechanism of action and expected effects By generating a distal to proximal pressure gradient and maintaining predefined pressure levels, the device is intended to promote lymphatic and venous return, support decongestion, and help prevent re accumulation of fluid in the affected limb. The device provides both dynamic and static compression. Expected clinical outcomes include reduction or stabilization of excess limb volume, favorable changes in tissue characteristics (e.g., stiffness, thickness), reduced infection frequency, improved quality of life, and acceptable comfort and adherence, with safety comparable to standard compression-based maintenance therapy.

Intended purpose and target population In this clinical investigation, the device is used as an adjunct compression modality in adult and adolescent patients with lower-limb lymphedema who are in the maintenance phase after prior decongestive treatment and for whom compression therapy is indicated. The device is designed to treat the lower limb (excluding the foot), either the whole limb or only its distal segment, and may also contribute to symptomatic management of limb edema of venous or mixed origin, and of lipoedema, according to physician prescription. The pressure level and daily duration of use are determined by the treating physician, and use is contraindicated in standard high risk situations for compression therapy (e.g., severe peripheral arterial disease, decompensated heart failure, septic thrombosis, certain neuropathies), as well as in individuals with known material allergy or significant motor/cognitive impairment.

Key design and safety features (non confidential) The system is a non pneumatic, electrically powered compression device with an internal rechargeable battery, intended for repeated use by a single patient and a projected service life of several years. Integrated sensors and control logic monitor wear time and adjust compression patterns according to patient activity, and the device includes automatic shut off after predefined periods in day and night modes to limit unintended overuse and to prompt strap readjustment as limb volume changes. The device is designed and tested in line with applicable medical device safety, usability, quality management, software lifecycle, and home use standards, and users receive risk based training on indications, contraindications, application, removal, maintenance, and troubleshooting before use in the trial.

Clinical investigation use and traceability For the study, several model sizes are available to accommodate different limb lengths, all used with a supplied protective liner and allocated according to a sizing table. All investigational units are specifically labeled for clinical investigation use only, tracked by batch and serial number from manufacturer to site and participant, stored under controlled conditions, and documented in accountability logs; defective units are returned to the manufacturer according to predefined procedures. No additional medical or surgical procedures are required for device use, and investigators and staff receive hands on training to ensure correct fitting, operation, and safety monitoring in accordance with good clinical practice and relevant MDCG guidance.

Description of the comparator The comparator in this study is current standard compression-based maintenance therapy for lower-limb lymphedema, including prescribed compression garments and all adjunct compression devices used in routine care. Both study groups are encouraged to follow usual compression recommendations, and the investigational device is evaluated against this real life mix of therapies rather than a single product.

Compression garments Daily use of custom-fitted daytime compression garments at higher pressure classes (approximately 30-40 mmHg) is the cornerstone of maintenance treatment after intensive decongestive therapy. Night-time compression is strongly encouraged whenever possible, in line with national recommendations, to prevent re accumulation of fluid and loss of the volume reduction achieved during the intensive phase. Donning and doffing aids are often required due to high compression levels and garment stiffness, and adherence may be limited by complexity and discomfort.

Multicomponent bandaging Short-stretch, multilayer or multicomponent bandages, with or without padding, are used as an adjunct decongestive technique, particularly when more intensive volume control is needed. Their effectiveness relies on high working pressures generated during walking or exercise, which produce pressure variations at the skin-bandage interface and enhance lymphatic drainage. Despite long learning curves, reduced interface pressure over time, and challenging self-management, multicomponent bandages remain one of the most effective decongestive compression modalities, with sustained pressures up to approximately 60-70 mmHg considered an upper effective range.

Compression wraps Inelastic or short-stretch wrap systems with hook-and-loop closures are widely used, especially for night-time self-management during the maintenance phase. They are easier to apply, remove, and readjust than bandages or high class garments, allowing patients to retighten the device when pressure decreases. Wraps typically provide mild to moderate constant pressure (around 20-30 mmHg), are useful for individuals who cannot manage garments, but are bulkier and less cosmetically acceptable.

Intermittent pneumatic compression Intermittent pneumatic compression (IPC) devices are commonly used as an adjunct to garments, sometimes as part of complete decongestive therapy. These devices use inflatable chambers, often arranged distally to proximally, to deliver sequential or gradient compression; chamber overlap can create localized pressures higher than the nominal setting, but IPC is generally considered safe for home and clinical use. There is no standardized regimen for IPC, and in practice sessions typically last 30-60 minutes once or twice daily, with frequency and duration adapted to patient needs and resources Benefits and risks of the IMD and clinical investigation The clinical investigation is designed to offer potential symptomatic, functional, and socio economic benefits while exposing participants only to low to moderate risks that are typical for external compression therapy and are mitigated through design, training, and monitoring measures. Overall, based on available data and current standards of care, the anticipated benefit risk profile is considered acceptable for conducting this study.

Potential benefits Participants may gain early access to an innovative dynamic compression device intended to improve lower limb volume maintenance and possibly ongoing decongestion during the maintenance phase of lymphedema treatment. Enhanced therapeutic education, including objective limb measurements and feedback on compression behavior, is expected to support greater autonomy and more effective self management at home. If effective, the device may help sustain volume reduction, reduce symptom burden and complications such as infections, improve mobility and quality of life, and lessen the need for complex bandaging or intensive re treatment. At a scientific level, the trial will generate detailed real life data on treatment strategies, tissue characteristics, measurement tools, adherence, and costs, which may advance understanding of lymphedema pathophysiology and inform optimization of maintenance protocols and future device design.

From a healthcare system perspective, improved self management and more efficient compression could reduce hospitalizations, outpatient visits, travel, and work absenteeism associated with poorly controlled lymphedema. Better long term adherence and fewer infectious episodes may lower direct and indirect costs and optimize use of specialist resources, especially if effective treatment can increasingly be delivered at home or in local facilities.

Exposure to treatments Participants in the investigational group will continue to use their prescribed elastic compression garments according to their usual preferences, with the addition of a personalized investigational device applied for a minimum daily duration, typically at the end of the day. Control group participants will receive standard maintenance phase management with compression garments and other available compression devices, structured according to their preferences and clinical needs. Night time compression with garments or other devices, including the investigational device where applicable, is encouraged in both groups to reflect routine practice and current recommendations.

Known and anticipated risks The investigational system is a non invasive external compression device, so risks are similar to those of established compression therapies and are generally considered low to moderate in severity. Anticipated adverse effects include local skin reactions (redness, irritation, pressure marks, itching), discomfort or pain, transient bruising, and paresthesia, most of which are expected to be mild and reversible with appropriate adjustment or discontinuation. Device related risks such as malfunction, incorrect application, or inadequate adjustment may lead to suboptimal compression, dissatisfaction, or-rarely-excessive localized pressure with potential worsening of symptoms or tourniquet effects. Serious complications (e.g., ischemic injury, nerve damage, venous thromboembolism, severe infection, or allergic reactions) are considered very rare when compression is used within recommended indications and pressure ranges, but will be actively monitored in the trial.

No specific risks are anticipated for healthcare professionals or caregivers beyond standard handling of external medical devices. No interactions with concomitant pharmacological treatments are expected, as the device acts locally through mechanical compression rather than systemic effects.

Risk mitigation measures Risk management has been conducted according to current standards for medical devices, including systematic identification, evaluation, and control of hazards related to design, materials, manufacture, and use. Mitigation measures include preclinical testing (e.g., biocompatibility, electrical and electromagnetic safety, mechanical and reliability testing), clear design features such as automatic shut off, emergency release, activity adapted compression patterns, and use of a non compressive protective liner to limit skin irritation. Investigators and study staff receive structured training on indications, contraindications, sizing, application, and removal of the device, and participants are enrolled under strict inclusion/exclusion criteria that avoid known high risk populations for compression.

The clinical protocol provides for regular follow up, predefined procedures for adverse event detection, documentation and reporting, and immediate discontinuation in case of ischemic signs, neurological symptoms, significant discomfort, or other safety concerns. A data monitoring process, including predefined stopping rules and interim safety review, allows the sponsor to pause or terminate the investigation if an unacceptable risk or serious safety signal is identified, and to implement corrective actions consistent with good clinical practice and regulatory guidance.

Benefit-risk assessment Study procedures are aligned with standard maintenance phase management in reference lymphedema centers, and additional trial related assessments are non invasive and designed to minimize discomfort and burden. Given the potential for improved limb volume control, reductions in symptoms and complications, enhanced autonomy, and meaningful socio economic and scientific gains, weighed against a risk profile comparable to existing compression therapies and mitigated through comprehensive risk management and monitoring, the overall benefit-risk ratio of the investigation is considered favorable for the target population. The study is intended to provide the clinical evidence needed to confirm the device's safety and performance and to refine the benefit-risk determination as part of its conformity assessment under the EU Medical Device Regulation.

Purpose of the clinical investigation The clinical investigation is designed to evaluate whether the investigational dynamic compression device (DDS), used alongside standard compression garments, is safe and effective for maintaining lower limb volume in the maintenance phase of lymphedema treatment, in line with EU MDR and GCP requirements.

Primary purpose and regulatory context The Clinical Investigation Plan aims to generate robust clinical evidence on the safety, performance, and clinical benefits of the DDS in patients with primary or secondary lower limb lymphedema who have completed an intensive decongestive phase and achieved a predefined volume reduction. The study is planned and conducted according to EU Medical Device Regulation 2017/745 (Annex XV) and ISO 14155, with clearly defined endpoints, eligibility criteria, monitoring, and a statistical analysis plan to support a future CE marking process.

Main objective and central hypothesis The main objective is to assess the ability of the DDS to maintain the reduction in excess limb volume achieved during intensive treatment over the maintenance phase. The key hypothesis is that the DDS, when used in combination with compression garments, is non-inferior in maintaining excess volume reduction than all currently available compression devices used as stand alone or in combination with garments in routine self managed care.

Clinical relevance and rationale In current practice, intensive complete decongestive therapy can reduce lower limb excess volume by around one third, but the subsequent maintenance phase is often marked by a rebound of at least half of this gain due to limited effectiveness and poor adherence to multicomponent bandaging and other adjuvant devices. The DDS is intended to address these gaps by standardizing compression delivery, reducing operator dependence, and providing an at home modality with appropriate pressure ranges and gradients that may sustain or further improve decongestion in everyday conditions.

Anticipated advantages of the DDS The device is expected to enhance patient autonomy in the maintenance phase by offering a lightweight, easier to apply system that can dynamically and automatically adjust compression in real time to the mechanical response of the edema. Its design aims to maintain a controlled distal to proximal pressure gradient, reduce the risk of tourniquet effects seen with suboptimal bandaging or some pneumatic systems, support greater mobility during use, and thereby improve adherence, clinical effectiveness, and overall quality of life while also potentially lowering direct and indirect costs and infection frequency.

Population and scope Inclusion and exclusion criteria are structured to minimize foreseeable risks while allowing an objective outpatient evaluation of the DDS across different stages of lower limb lymphedema, provided that at least a 20% excess volume reduction vs the contralateral limb has been achieved during the preceding intensive phase. The resulting data are intended to substantiate the manufacturer's safety and performance claims and to characterize the DDS benefit-risk profile in the context of contemporary maintenance phase management.

Study Design The clinical investigation is a 12 week, multicenter, randomized, assessor blinded trial designed to evaluate the safety and performance of a non CE marked Class IIa dynamic compression device (DDS) for maintenance phase lower limb lymphedema. It compares DDS plus standard compression garments with current real life compression based maintenance strategies across several European reference centers.

Overall design The study is prospective, interventional, pivotal, and confirmatory, conducted in outpatient maintenance phase patients following an intensive decongestive treatment. Participants are randomized 1:1 to two parallel arms and followed for 12 weeks, with structured measurements at baseline, week 6, and week 12, plus a safety follow up (7 ± 5 days) contact after completion.

Treatment arms and concomitant care In the DDS group, patients continue prescribed elastic compression garments at least during the day (and as often as possible at night) and use the DDS device as a dynamic wrap for at least 2 hours at the end of the day, without an elastic garment and without any other compression modalities. In the control group, patients use their prescribed elastic garments similarly and may freely use any other currently available compression devices and treatments permitted in routine care, except for predefined prohibited adjuvant therapies (e.g., lymphatic taping, laser, shockwave, certain pharmacological or surgical interventions). Manual lymphatic drainage, exercise, skin care, and lifestyle measures remain allowed in both groups to align with best practice maintenance phase management.

Sites, population, and follow up The trial is conducted at leading lymphedema reference centers in France, and Germany and is grounded in their standard maintenance phase prescriptions. Potential participants are identified during inpatient intensive treatment, receive written information and at least 5 days to decide, and are screened for eligibility (including ≥20% excess volume reduction and limb size compatibility) before discharge; women of childbearing potential undergo pregnancy testing. Because the device is considered low risk with no expected delayed effects, post trial safety follow up in the main study consists of a phone call approximately 7 days after the 12 week period, with additional optional long term observation in an ancillary study (up to 3 years or until CE marking).

Randomization and blinding Treatment allocation is performed centrally via secure web based randomization using site specific lists with varying block sizes, prepared by an independent statistician; sealed envelopes provide a backup if online access is unavailable. Randomization occurs after the baseline visit (V1) on the last inpatient day to minimize bias, and participants previously enrolled in a related intensive phase DDS study are randomized de novo. Outcome assessors are blinded to group allocation, while patients and treating staff are necessarily aware of the assigned treatment.

Study visits, procedures, and outcomes Three in person measurement sessions (V1 at baseline, V2 at week 6 ± 7 days, V3 at week 12 ± 7 days) each last about 60-75 minutes and include a comprehensive set of standard and advanced assessments (e.g., limb photographs, anthropometry, tape measurements, thermal imaging, 3D scanning, water volumetry, ultrasound, viscoelasticity, pitting, quality of life instruments, infection history, and patient reported comfort and usability at V3). Between visits, weekly electronic patient reported outcomes capture safety events, device wear time (DDS group), and the type, frequency, duration, and cost of compression therapies (control group) to support safety and cost effectiveness analyses.

Ancillary long term follow up Participants who complete the main study may be invited to an observational ancillary follow up to collect long term data on safety, durability, usage patterns, satisfaction, and adherence over the device's expected life or until CE marking. In this extension, patients from the DDS arm keep their device, and control arm patients who agree to participate receive a new device for use according to the instructions for use.

Investigation Population The clinical investigation plans to enroll 98 participants with lower limb lymphedema, distributed across three European reference centers (approximately 32-33 participants per site) over about 12 months. Each participant will be followed for the first 3 months of their maintenance phase treatment. Participants are considered enrolled once they provide written informed consent after eligibility screening, and randomization occurs on the last day of their inpatient intensive treatment, before the baseline measurement visit.

Each site will maintain an enrollment log linking a coded participant ID to names and contact details, ensuring traceability while protecting confidentiality. The inclusion and exclusion criteria are designed to minimize risk by excluding individuals with acute or decompensated comorbidities and those who do not meet the device's indication/contraindication profile, which inevitably narrows external validity but enhances safety and internal validity. Certain patterns of lymphedema (e.g., isolated thigh involvement or simultaneous bilateral disease) are excluded to improve the precision of limb volume-based outcomes, although findings are expected to be informative for broader lower limb and potentially upper limb lymphedema populations. Vulnerable groups, including children, pregnant or breastfeeding women, immunocompromised individuals, and elderly participants, are not included in this trial.

Data Management The sponsor has full responsibility for trial quality, monitoring, data integrity, and data protection, using written procedures and systems that comply with ISO 14155, MDR, GDPR, and the CIP.

Quality management and monitoring The sponsor oversees trial design, conduct, monitoring, data handling, reporting, and archiving, supported by written SOPs and documentation of compliance for all parties. Monitoring is risk-based and proportionate to the low risk profile of the device, and is performed before, during, and after the trial according to a predefined monitoring plan. On site and remote monitoring verify participant rights and safety, protocol and GCP compliance, and accuracy and consistency of data in the (e)CRF, with findings documented in monitoring reports shared with investigators.

Data Monitoring Committee An independent, multidisciplinary Data Monitoring Committee (DMC) monitors participant safety and overall study conduct and advises on continuation, modification, or termination based on interim analyses. The DMC reviews interim safety data (and descriptive efficacy data if needed), evaluates protocol adherence and data quality, and may recommend design modifications or trial suspension if safety or conduct concerns arise, without unblinding investigators or sponsor staff to comparative results. The DMC operates under a written charter and meets before trial initiation, at interim analysis, at study end, and ad hoc if urgent safety issues occur.

Data management and eCRF Participants are pseudonymized using coded identifiers, with linkage to personal data maintained separately in controlled site logs. Data are captured by trained site staff in an electronic CRF developed to reflect the CIP schedule, with structured tabs, audit trails, and role based access, and all entries and corrections are signed, dated, and traceable. The eCRF incorporates built in messaging for queries, chronological organization of measurements, tab locking after completion, and a full audit trail of any post lock changes, ensuring authenticity, accuracy, and traceability.

Data cleaning, lock, and archiving Data are regularly reviewed by the monitor and sponsor via secure remote access; data cleaning uses descriptive checks to identify missing, inconsistent, or erroneous entries, which are resolved via documented queries and backed up corrections. Once all queries are resolved and source verification completed, the database is locked (documented by a freeze certificate), and essential documents and datasets are archived for at least 15 years by the sponsor, with local archiving by investigators in line with institutional rules. Trial documents become part of the device technical documentation under the manufacturer's quality system.

Data protection, pseudonymization, and security All processing of personal data complies with GDPR, including data minimization, pseudonymization (with separate storage of code keys), and clear information in the informed consent on data use, access, and publication. Pseudonymized trial data are stored on encrypted institutional servers with regular backups, with additional encrypted local backups and strictly controlled access to code keys; all data used for publication are anonymized. Technical and organizational security measures include encrypted devices, secure networks, strong passwords and user IDs, restricted authorizations, audit logs, secure file sharing, validated electronic systems, and documented backup and disaster recovery procedures.

CIP Deviations Investigators must follow the Clinical Investigation Plan (CIP) as approved; deviations are only permitted in emergencies to protect participants, and the trial includes defined processes for managing deviations, disqualifying investigators if needed, and suspending or terminating the study where safety or conduct concerns arise.

Deviations from the CIP are allowed only when necessary to protect a participant's rights, safety, or well being in an emergency, and must then be documented and reported promptly to the sponsor and ethics committee (EC). All deviations are recorded (e.g., in a deviation log or serious breach form), graded by the sponsor, and followed by corrective and preventive actions (CAPA), including immediate risk mitigation, root cause analysis, possible process or document revision, and targeted retraining. Serious breaches are reported to regulatory authorities within specified timelines (e.g., 7 days), and all CAPA are periodically audited for effectiveness to protect data integrity and regulatory compliance.

Suspension or Early Termination The sponsor, PI, ECs, or national competent authorities may suspend or terminate the trial (or a single site) if there is evidence or suspicion of unacceptable risk, serious or repeated protocol violations, or other major issues in trial conduct. Safety driven suspensions or terminations must be reported to regulators within short timelines (e.g., within 24 hours for safety related halts and within 15 days for other premature terminations), and participants must be informed and followed up appropriately. If the study is temporarily halted, a formal risk assessment, corrective actions, and regulatory/EC approvals are required before resuming; all such events and their rationale are documented in the clinical investigation report.

Statistical Considerations Primary endpoint analysis uses ANCOVA with treatment group, baseline volume, and site as fixed factors, estimating mean difference with 95% CI and p-value for superiority.

Both per-protocol (PP) and intention-to-treat (ITT) analyses will be conducted. If non-inferiority is concluded as secondary two-sided t-test superiority analysis will be carried out.

Sample size calculation: powered at 80% to detect the non-inferiority margin with a two-sided α of 0.05, accounting for dropout and design effect, resulting in an adjusted 98 participants distributed across three sites.

Secondary/Exploratory: Secondary endpoints (continuous and categorical) are analyzed descriptively/exploratorily using linear or mixed-effects models and appropriate tests, with measurement agreement assessed via correlation and Bland-Altman methods. Patient-reported outcomes and economic evaluations are included.

Safety analyses and interim safety monitoring will be conducted, with stopping criteria defined for overwhelming safety concerns.

Categorical outcomes: Chi-square/Fisher's exact for independent groups; McNemar test for paired/matched data Method Agreement: ICC, Bland-Altman plots; graphical correlation. Missing data: multiple imputation models under the Missing At Random (MAR) assumption.

Multiplicity: controlled using hierarchical structures and adjustments Exploratory subgroup and sensitivity analyses planned to assess the robustness and consistency of findings across subpopulations.

• Bias is mitigated by centralized concealed randomization, blinded outcome assessors, staff training, protocol pre-registration, and detailed documentation of exclusions and deviations.
• An interim safety analysis after about 50% of participants is planned; no interim efficacy or futility testing is conducted.
• Reporting follows CONSORT 2010 and ISO 14155:2020, covering participant flow, demographics, efficacy, safety,

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Prof. Jean-Paul Belgrado, PhD; Phone Number: +33 6 38 39 79 56; Email: jp.belgrado@gmail.com
• Study Contact Backup: Name: Velika V Stoitchkova, MSc; Phone Number: +359 882 40 55 33; Email: velika.stoichkova@gmail.com

Study Locations

• France
  • Montpellier, France, 34090
    • CHU Montpellier - Saint Eloi
    • Principal Investigator: Sandrine Mestre, MD
    • Contact: Sandrine Mestre, MD; Phone Number: +33 467 33 70 28; Email: s-mestre@chu-montpellier.fr
    • Contact: Isabelle Quéré, Prof; Phone Number: +33 467 33 70 28; Email: i-quere@chu-montpellier.fr
    • Sub-Investigator: Isabelle Quéré, Prof
  • Toulouse, France, 31059
    • CHU Toulouse - Rangueil
    • Principal Investigator: Julie Malloizel, MD
    • Contact: Julie Malloizel, MD; Phone Number: +33 668 91 58 67; Email: malloizel-delaunay.j@chu-toulouse.fr
    • Contact: Alessandra Bura-Rivière, Prof; Phone Number: +33 668 91 58 67; Email: bura-riviere.a@chu-toulouse.fr
    • Sub-Investigator: Alessandra Bura-Rivière, Prof
• Germany
  • Bavaria
    • Pommelsbrunn, Bavaria, Germany, 91224
      • Lympho-Opt Fachklinik fur Lymphologie
      • Contact: Franz-Josef Schingale, MD; Phone Number: +49 9154 911 200; Email: franz-josef.schingale@lympho-opt.de
      • Contact: Britta Bockelmann, MD; Phone Number: +49 (0)178 628 5376; Email: info@drb-bodensee.de
      • Principal Investigator: Franz-Josef Schingale, MD
      • Sub-Investigator: Britta Bockelmann, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group: Currently available compression devices; Control group: Currently available compression devices Patients in the control group will structure the maintenance phase treatment of their lower limb lymphoedema depending on personal preferences and the recommendations of their treating physician(s).	Device: Control 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).
Experimental: DDS group: Dynamic compression device (DDS); Patients in the DDS group will structure the maintenance phase of thier lower limb lymphodema treatment depending on their personal preferences and the recommendations of their treating physician(s).	Device: DDS group: Dynamic compression device (DDS); 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative excess limb volume (%)	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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks
Longitudinal change in the volume of the feet in ml	assessed by water volumetry (ValGrado method)	12 weeks
Dermal and subcutaneous tissue thickness in mm	assessed by ultrasound imaging	12 weeks
Compressibility of the skin and subcutaneous tissue in mm	assessed by ultrasound imaging under standardized weight	12 weeks
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.	12 weeks
Skin temperature of the affected limb (in C°)	based on far infrared thermography mapping	12 weeks
Lower limb contour changes	based on standardized photos and measurements of surface area in cm2	12 weeks
Depth of the pitting sign in mm	based on standardized measurements	12 weeks
Incremental cost-effectiveness ratio (ICER) of DDS versus CATP	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	12 weeks
Frequency of infectious episodes	collected via an ePROM on a weekly basis and by the investigator at V1, V2 and V3, including: Non-necrotizing dermo-hypodermitis; Lymphangitis	12 weeks
Patient-reported quality of life	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.	12 weeks
Patient's observance to compression therapy	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.	12 weeks
Patient comfort with compression therapy	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).	12 weeks
Long-term safety questionnaire (ancillary study)	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.	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.
Device-specific comfort, ease of use, and satisfaction (trial-specific questionnaire, DDS group)	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.	12 weeks
Mean total direct medical cost per participant over 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)	12 weeks
Number of lymphoedema treatment sessions per participant over 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	12 weeks
Number and cost of medical devices used per participant over 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	12 weeks
Mean out-of-pocket cost per participant over 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	12 weeks
Number of lymphoedema-related healthcare consultations and hospitalizations per participant over 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	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety outcome: Number of participants with adverse events and device-related safety issues over 12 weeks	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	12 weeks
Exploratory objectives: 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.	12 weeks
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.	12 weeks
Exploratory objective: 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, 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.	12 weeks

Collaborators and Investigators

• Sponsor: Jean-Paul Belgrado

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: May 2, 2026
• First Submitted That Met QC Criteria: May 16, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 16, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Non-inferiority trial; Complex decongestive therapy; Dynamic compression; Lymphoedema maintenance treatment; Limb volume reduction; Limb volume maintenance
• Other Study ID Numbers: DDS2 V1.3_11052026; CIV-25-10-054914 (Other Identifier: EUDAMED); ID-RCB: 2025-A0810-49 (Other Identifier: French National Competent Authority - ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No