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

Официальное название

Effectiveness and Cost-effectiveness of Lymphaticovenous Anastomosis for Cancer Patients Who Suffer From Chronic Peripheral Lymphedema: a Randomized Controlled Trial

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Change from baseline in the Lymph-ICF Score at 12 and 24 months [Срок оценки: 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).]

Вторичные конечные точки (6)

• Change from baseline in excess limb volume [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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).]
• Patient costs, QALYs, and incremental cost-effectiveness [Срок оценки: 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).]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Нидерланды · 3 центра

• Radboud University Medical Center — Nijmegen
• Maastricht University Medical Center — Maastricht
• Erasmus University Medical Center — Rotterdam

Публикации

• 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-20 PMID 38626967

Идентификаторы

NCT: NCT06082349 · NL84169.068.23 · 2021038374 · METC23-023

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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