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

NCT06082349 | Recruiting DMC

• 3 other identifiers: NL84169.068.232021038374METC23-023
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

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

Keywords

Lymphaticovenous anastomosis; Sham surgery; Microsurgery; LVA

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the Lymph-ICF Score at 12 and 24 months

  The Dutch version of the 'Lymphedema Functioning, Disability, and Health" (Lymph-ICF) questionnaire is used. There are two versions of the Lymph-ICF; one for the upper extremity and one for the lower extremity. The questionnaires assess the impairments in function, activity limitations, and participation restrictions of patients with lymphedema. It is a validated, disease-specific questionnaire, consisting of items across 5 domains. Each item is scored on a VAS, ranging from 0 to 100.

  Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annually during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).

Secondary Outcomes (6)

• Change from baseline in excess limb volume

  Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annually during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).

• Change from baseline in extremity circumference measured by the Upper and Lower Extremity Lymphedema (UEL and LEL) indices

  Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annually during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).

• Change from baseline in the use of conservative treatment

  Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annually during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).

• Postoperative complications

  Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annually during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).

• Patency of the LVA

  12 and 24 months post-operatively and afterwards annually during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).

Study Arms (2)

Lymphaticovenous anastomosis (LVA)

EXPERIMENTAL

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 lymphatic 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.

Procedure: Lymphaticovenous anastomosis

Sham surgery

SHAM COMPARATOR

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.

Procedure: Sham surgery

Interventions

Sham surgery PROCEDURE

Sham surgery involves the process of surgery, including local anesthesia and incisions, but no LVA is made.

Also known as: Placebo surgery, Simulated surgery, Surgical placebo

Sham surgery

Lymphaticovenous anastomosis PROCEDURE

Lymphaticovenous anastomosis (LVA) involves connecting a lymphatic vessel to an adjacent vein of similar size, thereby facilitating the outflow of lymphatic fluid in patients suffering from secondary lymphedema

Also known as: LVA, Lymphaticovenular anastomosis, Lymphovenous bypass, Lymphatic-venous shunt

Lymphaticovenous anastomosis (LVA)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Radboud University Medical Center: collaborator
• Erasmus Medical Center: collaborator

Study Sites (3)

Radboud University Medical Center

Nijmegen, Gelderland, 6525GA, Netherlands

RECRUITING

Maastricht University Medical Center

Maastricht, Limburg, 6229HX, Netherlands

RECRUITING

Erasmus University Medical Center

Rotterdam, South Holland, 3015GD, Netherlands

RECRUITING

Related Publications (1)

• Kleeven A, Jonis YMJ, Tielemans H, van Kuijk S, Kimman M, van der Hulst R, Vasilic D, Hummelink S, Qiu SS. The N-LVA Study: effectiveness and cost-effectiveness of lymphaticovenous anastomosis (LVA) for patients with cancer who suffer from chronic peripheral lymphoedema - study protocol of a multicentre, randomised sham-controlled trial. BMJ Open. 2024 Apr 15;14(4):e086226. doi: 10.1136/bmjopen-2024-086226.

  PMID: 38626967 BACKGROUND

Related Links

• Study website

MeSH Terms

Conditions

Lymphedema; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Shan Shan Qiu Shao, MSc, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

• Stefan Hummelink, MSc, PhD

  Radboud University Medical Center

  STUDY CHAIR

• Dalibor Vasilic, MSc, PhD

  Erasmus Medical Center

  STUDY CHAIR

Central Study Contacts

Tanya Wolffenbuttel, MSc

CONTACT

+31(0)433877481; t.wolffenbuttel@erasmusmc.nl/tanya.wolffenbuttel@mumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The researcher, research nurse and patients will be blinded. The blinded researcher and research nurse will perform the measurements during follow-up, as well as the assessment of the outcomes. Due to the nature of the study, the surgeon performing both procedures cannot be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, double-blind, randomized sham-controlled trial

Study Record Dates

• First Submitted: October 3, 2023
• First Posted: October 13, 2023
• Study Start: December 18, 2023
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: The data will become available upon request after the completion of the trial and publication of primary manuscripts. Individual participant data will be stored for a period of 15 years.
• Access Criteria: Request for data sharing of individual participant data (IPD) will be assessed individually by the principal investigator, considering them for appropriate research purposes after the completion of the trial.

Locations

NL (3)