The N-LVA Study: RCT Comparing LVA vs. Sham Surgery in Cancer-related Lymphedema

Maastricht University Medical Centre (MUMC)

Status: Enrolling

Conditions: Lymphedema Arm; Lymphedema of Upper Limb; Lymphedema, Lower Limb; Lymphedema, Secondary; Lymphedema of Leg

Treatments: Procedure: Lymphaticovenous anastomosis; Procedure: Sham surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT06082349

METC23-023 (Other Identifier)

2021038374 (Other Grant/Funding Number)

NL84169.068.23

Details and patient eligibility

About

The goal of this randomized controlled trial is to compare the effectiveness and cost-effectiveness of lymphaticovenous anastomosis (LVA) with sham surgery for patients suffering from unilateral cancer-related lymphedema in either the upper or lower extremity. It aims to answer whether LVA is more effective than sham surgery in terms of improvement in Lymph-ICF score.

A total of 110 participants will be allocated randomly into two groups at a 1:1 ratio. The first group will receive lymphaticovenous anastomosis (LVA), while the second group will undergo sham surgery.

Full description

One of the most debilitating side effects of cancer treatment is cancer-related lymphedema (CRL), with an overall incidence of 15.5%. To date, there is no definite cure for lymphedema. Conservative therapy, namely complex decongestive therapy is the golden standard for the treatment. Lymphaticovenous anastomosis (LVA) might be a promising treatment modality for patients with CRL, but available studies are small and the quality is lacking. No large-scale prospective or randomized studies have been published on the efficacy of LVA.

The main objective of this randomized controlled trial is to assess whether LVA is more effective than sham surgery in terms of improvement in Lymph-ICF score, volume reduction, reduction of complex decongestive therapy, and cost-effectiveness.

The study will take place in three centers in the Netherlands: Maastricht University Medical Center, Radboud University Medical Center, and Erasmus University Medical Center.

The patients will be randomly distributed into two groups: the LVA group or the Sham group. Both procedures are performed under local anesthesia. Patients in both groups are subject to minor surgical complications (wound infection, bleeding, wound dehiscence). Special care will be taken to prevent damage to lymphatic vessels in the Sham group, to allow a future LVA operation once the study ends. The follow-up moments will be at 3, 6, 12, 18, and 24 months. Additionally, a subset of patients will partake in an annual extended follow-up, ongoing until the start of the analysis. Each follow-up moment will last 45 minutes in total. The patient also receives two digital questionnaires at each follow-up moment.

Enrollment: 110 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Treated for cancer and underwent treatment of either axillary or inguinal lymph nodes or radiotherapy;
• Early stage lymphedema (ISL I-II) in the upper or lower extremity, and diagnosed by lymphoscintigraphy for the lower extremity;
• Unilateral lymphedema;
• Viable lymphatic vessels as determined by indocyanine green (ICG)Lymphography (stage II-III);
• Refractory lymphedema that underwent at least three months of conservative treatment;
• Informed consent.

Exclusion criteria

• History of lymphatic reconstruction in the past 10 years;
• Late-stage lymphedema of the extremity (ISL classification ≥ II lymphedema) with evident fat deposition and/or fibrosis;
• Patients with active distant metastases, treated with palliative intent;
• Patients with the active treatment of primary cancer, i.e. surgery, radiotherapy, and/or chemotherapy. Note: patients receiving adjuvant targeted and/or endocrine treatment are eligible;
• Edema due to venous insufficiency, evaluated by venous duplex ultrasound of the deep and superficial venous system;
• Active infection in the lymphedematous extremity;
• Bilateral lymphedema;
• Lymphedema present in genital or breast area only;
• Primary lymphedema;
• Non-viable lymphatic system as determined by ICG Lymphography (stages IV and V).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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110 participants in 2 patient groups

Lymphaticovenous anastomosis (LVA)

Experimental group

Description:

Patients in this group will undergo lymphaticovenous anastomosis at one or more locations on the affected limb, and the procedure will be performed under local anesthesia. During the operation, patients will be blinded using a noise-canceling headphone and blindfolds. Incisions will be made at the sites where lymphatic vessels are obstructed, ensuring no harm to the viable part of the lympahtic system. The locations will be determined prior to the surgery using ICG lymphography. The LVA(s) will be made in the subdermal plane with the aid of a surgical microscope. Generally, 1 to 4 LVAs are made. The LVA(s) is made using a surgical microscope and the operation will take approximately 60 to 90 minutes.

Treatment:

Procedure: Lymphaticovenous anastomosis

Sham surgery

Sham Comparator group

Description:

Patients in this group will undergo sham surgery at one location on the affected limb, and the procedure will be performed under local anesthesia. During the operation, patients will be blinded using a noise-canceling headphone and blindfolds. The locations for LVA surgery will be determined prior to the surgery using ICG lymphography. However, the incision for the sham procedure will be made 2 centimeters medial or lateral to the predetermined site. This is done in order to avoid damage to the lymph vessels as to allow for future LVA surgery. After the incision, no LVA is made. Rather than performing the actual operation, the plastic surgeon will simulate the procedure by applying pressure in the surgical area. To mimic the approximate duration of a regular LVA procedure, the sham operation will take approximately 60 to 90 minutes.

Treatment:

Procedure: Sham surgery