About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Parallel
Treatments tested in this trial
Lymphovenous Anastomosis
Procedure/SurgeryMicrosurgical creation of multiple lymphatic-venous connections in the most affected limb under general anaesthesia.
Complete Decongestive Therapy
Other interventionComplete Decongestive Therapy, comprising bandaging, skin care and exercise, followed by compression garments.
Treatment groups
Trial outcomes
Primary outcomes
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.
Secondary outcomes
Change in Limb Volume by Tape Measurement
Difference in limb volume using tape measurements and calculating using formulas.
Change in Limb Volume by Perometry
Difference in limb volume obtained with optoelectronic perometry (automatic three-dimensional scan of the leg).
Change in Limb Mass by DXA
Difference in limb mass of the affected leg measured with dual-energy X-ray absorptiometry.
Change in Compression Garment Use
Change of compression class, change in daily use, or continue/discontinue compression garments. Data collected by questionnaire.
Other outcomes
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.
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.
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.
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