Effect of Lymphovenous Anastomosis on Lower Limb Lymphedema: Pragmatic Randomized Controlled Trial
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Lymphovenous Anastomosis, Complete Decongestive Therapy.
- Who it may be relevant to
- Registry conditions: Lymphedema, Lymphoedema, Lymphoedema of Leg, Lymphedema of Leg. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Denmark
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Protocol: Effect of Lymphovenous Anastomosis in the Treatment of Lower Limb Lymphedema - Pragmatic Assessor-Blinded Open-Label Randomized Controlled Trial (PrCT)
Overview
This multicentre pragmatic randomised controlled trial evaluates lymphovenous anastomosis (LVA) for lower-limb lymphedema (LLL) in Denmark. Adults with unilateral or bilateral International Society of Lymphology (ISL) stage 1-2a LLL who have completed protocol-defined Complete Decongestive Therapy (CDT) are randomised 1:1 to Intervention arm - LVA surgery plus ongoing compression care Control arm - Compression care only Recruitment takes place at the Departments of Plastic Surgery, Herlev-Gentofte Hospital and Odense University Hospital. Outcomes are assessed by independent blinded staff at baseline, 6, 12 and 24 months. A biopsy substudy in ten LVA patients explores inflammatory and fibrotic changes. Primary endpoint is change in L-Dex ratio at 12 months. Secondary endpoints include limb volume, infection rate, lymphoscintigraphy findings, patient-reported outcomes, compression-garment use and anastomosis patency. The trial follows Good Clinical Practice and General Data Protection Regulation (GDPR). Patients are covered by the Danish public patient-compensation scheme. Results will be published regardless of outcome, and control participants may opt for LVA after the 12-month visit.
Detailed description
Lower-limb lymphedema (LLL) causes chronic swelling, pain, recurrent infections and impaired quality of life. Complete Decongestive Therapy (CDT) is standard care, yet many patients have persistent disease. Lymphovenous anastomosis (LVA) is a super-microsurgical procedure that diverts lymph into the venous system, but robust randomised evidence in LLL is lacking
This multicentre pragmatic randomised trial will test whether lymphovenous anastomosis (LVA) can reduce lower-limb lymphedema and improve life quality in adults who have completed Complete Decongestive Therapy (CDT). The study is carried out at two Danish university hospitals that routinely manage complex lymphedema. A computer system assigns participants in a 1:1 ratio to either LVA plus compression care or compression care alone. Surgeons create as many anastomoses as possible under general anaesthesia, using indocyanine green mapping to find suitable lymphatic vessels.
Adults aged 18 years or older with International Society of Lymphology stage (ISL) 1 or 2a lymphedema of one or both legs can join if they have finished CDT. Key exclusions are stage 2b or 3 disease, body-mass index (BMI) above 28, active cancer, severe medical illness, or prior lymphedema surgery.
The primary outcome is the change in L-Dex ratio, from baseline to 12 months. Secondary outcomes measured at baseline, 6, 12 and 24 months include limb volume by tape, perometry and dual-energy X-ray absorptiometry, infection frequency, lymphoscintigraphy findings, quality-of-life scores (Lymphedema Quality of Life Questionnaire (LYMQOL) and EuroQol Five Dimension Five Level (EQ-5D-5L)) and use of compression garments. At 12 months the patency of the anastomoses is checked with indocyanine green lymphography in the surgical arm. A small substudy in ten surgical participants will compare inflammatory markers and tissue structure in paired skin biopsies collected during surgery and again 6 months later.
Participants attend the clinic for baseline, 6-month and 12-month visits and return at 24 months for long-term follow-up. Conservative measures such as compression garments may continue (but not reduced in 12 months for LVA-group), but no other surgical or medical lymphedema procedures are allowed during the study period.
All data are entered into a secure electronic database and analysed according to Good Clinical Practice, the Danish Code of Conduct for Research Integrity and General Data Protection Regulation (GDPR). The regional research ethics committee has approved the protocol, and participants are covered by the Danish public patient-compensation scheme. Results will be published in peer reviewed journals no matter whether LVA shows benefit, harm or no difference.
Interventions
- Procedure Lymphovenous Anastomosis
Microsurgical creation of multiple lymphatic-venous connections in the most affected limb under general anaesthesia. - Other Complete Decongestive Therapy
Complete Decongestive Therapy, comprising bandaging, skin care and exercise, followed by compression garments.
Primary outcome measures
- Change in L-Dex ratio (bioimpedance spectroscopy) at 12 months. [Time frame: Baseline to 12 months]
Secondary outcome measures (8)
- Change in Limb Volume by Tape Measurement [Time frame: Baseline, 6 months, 12 months, 24 months]
- Change in Limb Volume by Perometry [Time frame: Baseline, 6 months, 12 months, 24 months]
- Change in Limb Mass by DXA [Time frame: Baseline, 6 months, 12 months, 24 months]
- Change in Compression Garment Use [Time frame: Baseline to 24 months]
- Incidence of Erysipelas Infections [Time frame: Baseline, 6 months, 12 months, 24 months]
- Change in Lymphoedema Quality of Life Questionnaire (LYMQOL) [Time frame: Baseline, 6 months, 12 months, 24 months]
- Change in EuroQol Five Dimension Five Level (EQ-5D-5L) utility index [Time frame: Baseline, 6 months, 12 months, 24 months]
- Change in Lymphoscintigraphy [Time frame: Baseline, 6 mo, 12 mo, 24 mo]
Eligibility criteria
Inclusion criteria
- LLL International Society of Lymphology (ISL) stage 1-2a (both primary and secondary lymphedema and both unilateral and bilateral)
- Cancer-free with no recurrence for at least one year
- Age 18 or above
- Circumference of the affected leg is at least 1 cm larger than the non-lymphedema leg at the most affected site of lymphedema.
- Proficiency in Danish language, and ability to provide informed consent.
- Dermal Backflow Stage 0-4
Exclusion criteria
- LLL International Society of Lymphology (ISL) stage 2b-3
- Medical conditions contraindicating surgical intervention or anesthesia, such as severe heart or lung disease
- Allergy to ICG
- Ongoing infections or skin diseases in the affected limb
- Previous surgery or other treatment modalities that could interfere with the study results (previous LVA, liposuction or similar).
- Dermal Backflow Stage 5
- Active cancer
- Heart or kidney conditions that can cause leg swelling
- A BMI above 28 kg/m²
- Current smoker
- Any foreign objects in the lower extremities (e.g., metal implants, prostheses)
- Venous insufficiency Unilateral weakness in the lower extremity (e.g., after a stroke)
- Known iodine allergy (contraindication for ICG injection)
- Leg length discrepancy (anisomelia) > 1.5 cm
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Single blind
- Primary purpose
- Treatment
Study locations
Denmark · 2 centers
- Department of Plastic Surgery, Odense University Hospital — Odense
- Department of Plastic Surgery, Herlev and Gentofte Hospital — Herlev
Identifiers
NCT: NCT07073586 · H-25012096