An interventional study of Lymphovenous Anastomosis and Complete Decongestive Therapy in Lymphedema, Lymphoedema and Lymphoedema of Leg, sponsored by Herlev and Gentofte Hospital. Recruiting at 2 sites in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-07-31.
Sponsored by Herlev and Gentofte Hospital · Not applicable, Interventional, and Treatment
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.
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.
560 studies on the registry are indexed under Lymphedema; 135 are open to participants now.
This study's planned enrollment of 66 is above the median of 50 across 403 interventional studies indexed under Lymphedema.
Browse Lymphedema studies →Herlev and Gentofte Hospital is the lead sponsor of 73 studies on the registry; 25 are open to participants now.
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Exclusion Criteria:
LVA + conservative care. Patient must have undergone Complete Decongestive Therapy (CDT) and comply with the compression treatment. Follow-up at 6, 12 and 24 months includes blinded assessment of L-Dex, tape and perometry volumes, DXA, lymphoscintigraphy, erysipelas incidence and LYMQOL/EQ-5D-5L scores; patency is checked by ICG-lymphography at 12 months. A subset of 10 patients with unilateral lymphedema also provides paired skin biopsies (both legs) at surgery and again 6 months postoperatively for biomarker and histological analysis.
Procedure: Lymphovenous Anastomosis · Other: Complete Decongestive Therapy
Conservative care alone. Participants complete standard Complete Decongestive Therapy, comprising bandaging, skin care and exercise, followed by compression garments. Outcomes are assessed by the same blinded schedule as the LVA arm at baseline, 6, 12 and 24 months. Participants may elect LVA crossover after the 12-month evaluation if desired.
Other: Complete Decongestive Therapy
Microsurgical creation of multiple lymphatic-venous connections in the most affected limb under general anaesthesia.
Complete Decongestive Therapy, comprising bandaging, skin care and exercise, followed by compression garments.
Also known as: CDT
Change in L-Dex ratio (bioimpedance spectroscopy) at 12 months.
Difference in L-Dex ratio of the most affected leg, measured with the SOZO bioimpedance device (ImpediMed). Measurements are performed by blinded assessors after 48 h without compression garments.
Time frame: Baseline to 12 months
Change in Limb Volume by Tape Measurement
Difference in limb volume using tape measurements and calculating using formulas.
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Limb Volume by Perometry
Difference in limb volume obtained with optoelectronic perometry (automatic three-dimensional scan of the leg).
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Limb Mass by DXA
Difference in limb mass of the affected leg measured with dual-energy X-ray absorptiometry.
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Compression Garment Use
Change of compression class, change in daily use, or continue/discontinue compression garments. Data collected by questionnaire.
Time frame: Baseline to 24 months
Incidence of Erysipelas Infections
Number of erysipelas episodes in the affected limb
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Lymphoedema Quality of Life Questionnaire (LYMQOL)
Difference in total score of the Lymphoedema Quality of Life Questionnaire for lower limb lymphedema. Item and domain scores run from 1 to 4. Higher scores mean a worse quality of life. The separate "overall quality of life" item uses a 0 to 10 scale. Higher scores mean a better quality of life.
Time frame: Baseline, 6 months, 12 months, 24 months
Change in EuroQol Five Dimension Five Level (EQ-5D-5L) utility index
Using the Danish value set, scores range from -0.757 (worst imaginable health) to 1.000 (full health). Higher scores mean a better health-related quality of life
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Lymphoscintigraphy
Change in lymphoscintigraphy transport. Scans read by blinded nuclear-medicine specialists.
Time frame: Baseline, 6 mo, 12 mo, 24 mo
Patency of Lymphovenous Anastomoses
Proportion of anastomoses that remain patent on indocyanine green (ICG) lymphography performed in the LVA group. Patency defined as visible dye passage through the anastomosis.
Time frame: 12 months
Change in Biomarkers in Skin Biopsies
Change in expression of cytokines and growth factors in paired biopsies from affected and contralateral legs of 10 LVA participants.
Time frame: Baseline (intra-operative) to 6 months
Change in Histological Features in Skin Biopsies
Difference in histology and immunohistochemistry on the same paired biopsies in paired biopsies from affected and contralateral legs of 10 LVA participants.
Time frame: Baseline (intra-operative) to 6 months
Plan to share: No
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