Clinical trial NCT06082349: The N-LVA Study: RCT Comparing LVA vs. Sham Surgery in Cancer-related Lymphedema
Official title: Effectiveness and Cost-effectiveness of Lymphaticovenous Anastomosis for Cancer Patients Who Suffer From Chronic Peripheral Lymphedema: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lymphedema, Secondary
Lymphedema of Upper Limb
Lymphedema, Lower Limb
Lymphedema Arm
Lymphedema of Leg
Keywords: Lymphaticovenous anastomosis
Sham surgery
Microsurgery
LVA
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
name: Erasmus Medical Center
First posted: 2023-10-13
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, double-blind, randomized sham-controlled trial
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change from Baseline in the Lymph-ICF Score at 12 and 24 months
timeFrame: Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annualy during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).
Secondary outcomes:
measure: Change from baseline in excess limb volume
timeFrame: Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annualy during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).
measure: Change from baseline in extremity circumference measured by the Upper and Lower Extremity Lymphedema (UEL and LEL) indices
timeFrame: Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annualy during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).
measure: Change from baseline in the use of conservative treatment
timeFrame: Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annualy during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).
measure: Postoperative complications
timeFrame: Baseline, 3, 6, 12, 18 and 24 months post-operatively and afterwards annualy during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).
measure: Patency of the LVA
timeFrame: 12 and 24 months post-operatively and afterwards annualy during the extended follow-up, lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).
measure: Patient costs, QALYs, and incremental cost-effectiveness
timeFrame: , lasting up to the start of the first analysis (maximally 3 years extra or 3 additional visits).
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
state: Zuid-Holland
Study officials:
affiliation: Maastricht University Medical Center
name: Shan Shan Qiu Shao, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Stefan Hummelink, MSc, PhD
role: STUDY_CHAIR
affiliation: Erasmus Medical Center
name: Dalibor Vasilic, MSc, PhD
role: STUDY_CHAIR
References:
citation: 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.