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

NCT ID: NCT07073586

Last Updated: 2025-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-09

Study Completion Date

2029-08-31

Brief Summary

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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

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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.

Conditions

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Lymphedema Lymphoedema Lymphoedema of Leg Lymphedema of Leg

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Two-arm, assessor-blinded, open-label, pragmatic randomized controlled trial comparing LVA plus conservative therapy with conservative therapy alone.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Outcome assessors remain unaware of group allocation; participants wear adhesive bandage over potential incision sites at follow-up visits.

Study Groups

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Lymphovenous anastomosis (LVA) + Compression Therapy

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.

Group Type EXPERIMENTAL

Lymphovenous Anastomosis

Intervention Type PROCEDURE

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

Complete Decongestive Therapy

Intervention Type OTHER

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

Compression Therapy Alone

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.

Group Type ACTIVE_COMPARATOR

Complete Decongestive Therapy

Intervention Type OTHER

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

Interventions

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Lymphovenous Anastomosis

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

Intervention Type PROCEDURE

Complete Decongestive Therapy

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

Intervention Type OTHER

Other Intervention Names

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CDT

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Herlev and Gentofte Hospital

OTHER

Sponsor Role lead

Responsible Party

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Amar Bucan

Medical doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lisbet Rosenkrantz Hölmich, MD, Professor, DMSc

Role: STUDY_CHAIR

Department of Plastic Surgery, Herlev and Gentofte Hospital, Denmark

Locations

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Department of Plastic Surgery, Odense University Hospital

Odense, Fyn, Denmark

Site Status NOT_YET_RECRUITING

Department of Plastic Surgery, Herlev and Gentofte Hospital

Herlev, Region Sjælland, Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Amar Bucan, Medical doctor

Role: CONTACT

+4538685444

Facility Contacts

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Jørn Bo Thomsen, MD, PhD

Role: primary

+45 65 41 24 45

Amar Bucan, Medical doctor

Role: primary

+4538689045

Lisbet Rosenkrantz Hölmich, MD, Professor, DMSc

Role: backup

+4538689045

Other Identifiers

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H-25012096

Identifier Type: -

Identifier Source: org_study_id

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