Effect of Lymphovenous Anastomosis on Lower Limb Lymphedema: Pragmatic Randomized Controlled Trial

NCT07073586 | Recruiting

• 1 other identifier: H-25012096
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Lymphedema; Lymphoedema; Lymphoedema of Leg; Lymphedema of Leg

Keywords

Lymphovenous Anastomosis; LVA; Lower Limb Lymphedema; Leg Lymphedema; Randomized Controlled Trial; CDT; Compression Therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 12 months

Secondary Outcomes (8)

• Change in Limb Volume by Tape Measurement

  Baseline, 6 months, 12 months, 24 months

• Change in Limb Volume by Perometry

  Baseline, 6 months, 12 months, 24 months

• Change in Limb Mass by DXA

  Baseline, 6 months, 12 months, 24 months

• Change in Compression Garment Use

  Baseline to 24 months

• Incidence of Erysipelas Infections

  Baseline, 6 months, 12 months, 24 months

Other Outcomes (3)

• Patency of Lymphovenous Anastomoses

  12 months

• Change in Biomarkers in Skin Biopsies

  Baseline (intra-operative) to 6 months

• Change in Histological Features in Skin Biopsies

  Baseline (intra-operative) to 6 months

Study Arms (2)

Lymphovenous anastomosis (LVA) + Compression Therapy

EXPERIMENTAL

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

Compression Therapy Alone

ACTIVE COMPARATOR

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

Interventions

Lymphovenous Anastomosis PROCEDURE

Microsurgical creation of multiple lymphatic-venous connections in the most affected limb under general anaesthesia.

Lymphovenous anastomosis (LVA) + Compression Therapy

Complete Decongestive Therapy OTHER

Complete Decongestive Therapy, comprising bandaging, skin care and exercise, followed by compression garments.

Also known as: CDT

Compression Therapy Alone; Lymphovenous anastomosis (LVA) + Compression Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Herlev and Gentofte Hospital: lead

Study Sites (2)

Department of Plastic Surgery, Odense University Hospital

Odense, Fyn, 5, Denmark

NOT YET RECRUITING

Department of Plastic Surgery, Herlev and Gentofte Hospital

Herlev, Region Sjælland, 2730, Denmark

RECRUITING

MeSH Terms

Conditions

Lymphedema

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Lisbet Rosenkrantz Hölmich, MD, Professor, DMSc

  Department of Plastic Surgery, Herlev and Gentofte Hospital, Denmark

  STUDY CHAIR

Central Study Contacts

Amar Bucan, Medical doctor

CONTACT

+4538685444; amar.bucan.02@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors remain unaware of group allocation; participants wear adhesive bandage over potential incision sites at follow-up visits.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical doctor

Model Details: Two-arm, assessor-blinded, open-label, pragmatic randomized controlled trial comparing LVA plus conservative therapy with conservative therapy alone.

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: July 18, 2025
• Study Start: May 9, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)