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

NCT ID: NCT06082349

Last Updated: 2026-01-16

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

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-18

Study Completion Date

2029-03-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicenter, double-blind, randomized sham-controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
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.

Study Groups

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Lymphaticovenous anastomosis (LVA)

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.

Group Type EXPERIMENTAL

Lymphaticovenous anastomosis

Intervention Type 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

Sham surgery

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.

Group Type SHAM_COMPARATOR

Sham surgery

Intervention Type PROCEDURE

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

Interventions

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Lymphaticovenous anastomosis

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

Intervention Type PROCEDURE

Sham surgery

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

Intervention Type PROCEDURE

Other Intervention Names

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LVA Lymphaticovenular anastomosis Lymphovenous bypass Lymphatic-venous shunt Placebo surgery Simulated surgery Surgical placebo

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role collaborator

Maastricht University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shan Shan Qiu Shao, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Stefan Hummelink, MSc, PhD

Role: STUDY_CHAIR

Radboud University Medical Center

Dalibor Vasilic, MSc, PhD

Role: STUDY_CHAIR

Erasmus Medical Center

Locations

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Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Site Status RECRUITING

Erasmus University Medical Center

Rotterdam, South Holland, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Tanya Wolffenbuttel, MSc

Role: CONTACT

Facility Contacts

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Tanya Wolffenbuttel, MSc

Role: primary

Tanya Wolffenbuttel, MSc

Role: primary

Tanya Wolffenbuttel, MSc

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 38626967 (View on PubMed)

Related Links

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Other Identifiers

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2021038374

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

METC23-023

Identifier Type: OTHER

Identifier Source: secondary_id

NL84169.068.23

Identifier Type: -

Identifier Source: org_study_id

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