Added Value of Reconstructive Lymphatic Surgery to Usual Care in Lymphoedema

Official title

Comparison of Reconstructive Lymphatic Surgery Versus no Surgery, Additional to Decongestive Lymphatic Therapy (Usual Care), for the Treatment of Iymphoedema, Through a Multicentre Randomised Controlled Trial

Overview

The primary objective of this research proposal is to investigate * in patients with lymphoedema of the upper limb or lower limb (P) * the added value of reconstructive lymphatic surgery (I) * to the decongestive lymphatic therapy (usual care) (C) * on the lymphoedema-specific quality of life (QoL) (O) * at 18 months post-surgery/ no surgery (T) Consequently, a multicentre pragmatic randomised controlled trial is performed to give an answer on following research question: 'Is, in addition to usual care - i.e. decongestive lymphatic therapy -, reconstructive lymphatic surgery (intervention group) superior to no surgery (control group), for the treatment of upper or lower limb lymphoedema?'

Detailed description

Lymphoedema is a chronic and often debilitating condition caused by lymphatic insufficiency. It leads to swelling of the limb and an increased risk of infection. It can be classified as primary (congenital) or secondary (acquired) lymphoedema.

Lymphoedema is very burdensome for the patient and therefore is it often associated with mental problems for example frustration and stress. In addition, because of the increase in volume of the limb, patients also develop physical problems, such as pain, heaviness, loss of strength, and develop functional problems, such as problems with household, mobility or social activities. These mental, physical and functional problems all have a negative impact on quality of life and have an influence on the ability to work. Consensus exist that the first choice of treatment is a conservative treatment. This conservative treatment consists of skin care, compression therapy (i.e. multilayer bandaging and compression garments), exercises and lymph drainage. Reconstructive lymphatic surgery is another option, also often performed: i.e. lymphovenous anastomoses, on the one hand, and a lymph node transfer, on the other hand. By (partially) restoring the lymphatic transport, the reconstructive lymphatic surgery may possibly lead to a larger decrease of the lymphoedema volume and therefore greater discontinuation of the compression garment. Consequently, patients will have an improvement in functioning and quality of life.

Currently, scientific evidence for reconstructive lymphatic surgery for the treatment of lymphoedema is missing. Therefore, the aim of this trial is to investigate the added value of reconstructive lymphatic surgery of the lymphatic system in addition to the conservative treatment, for the treatment of lymphoedema.

Interventions

• Other Usual care
  Home physical therapist performs usual care and educates the patient to perform self-management Usual care: M1-6: 6 months of maintenance decongestive lymphatic therapy (DLT) (by patient and home physical therapist): * week 1-2: no physical therapy; patient performs limb elevation, muscle contractions and wears the bandage (intervention group)/ compression garment (control group) * week 3-4: start physical therapy, 2 days/ week: exercises, skin care \& manual lymph drainage (MLD), education;
• Procedure Reconstructive lymphatic surgery
  For the procedure of LVA: \- Aim: making anastomoses of lymph vessels at the capillary level with a diameter of 0.3 to 0.8 mm, to redirect lymph to venous stream directly For the procedure of LNT: \- Aim: 1. Placed lymph nodes act as sponge to absorb lymphatic fluid and direct it into the vascular network; 2. Placed lymph nodes induce lymphangiogenesis

Primary outcome measures

• Lymphoedema-specific QoL (or problems in functioning related to development of lymphoedema) [Time frame: at 18 months]

Secondary outcome measures (12)

• Lymphoedema-specific QoL (or problems in functioning related to development of lymphoedema) [Time frame: at 1, 3, 6, 12 (short term) and 24, 36 (longer term) months]
• General health-related QoL [Time frame: at 1, 3, 6, 12, 18, 24, 36 months]
• Limb volume [Time frame: at 1, 3, 6, 12, 18 (key secondary outcome), 24, 36 months]
• Failure to reduce the hours a day of wearing the compression stocking [Time frame: at 12, 18, 24, 36 months]
• The hours of wearing the compression garment during one week [Time frame: at 12, 18 (key secondary outcome), 24, 36 months]
• The experience of the compression garment [Time frame: at 1, 3, 6, 12, 18, 24, 36 months]
• The physical activity level [Time frame: at 1, 3, 6, 12, 18, 24, 36 months]
• The need for intensive treatment due to an increase in lymphoedema volume [Time frame: at 6, 12, 18, 24, 36 months]
• Body weight [Time frame: at 1, 3, 6, 12, 18, 24, 36 months]
• Work capacity [Time frame: at 1, 3, 6, 12, 18, 24, 36 months]
• Work ability [Time frame: at 1, 3, 6, 12, 18, 24, 36 months]
• Infection during the previous 18 months (yes/no) [Time frame: at 18, 36 months (adverse events are collected during each clinical assessment but the amount of infections as secondary outcome are taken together for statistical analyses per 18 months)]

Eligibility criteria

Inclusion criteria

• Unilateral or bilateral, primary or secondary lymphoedema of the upper or lower limb
• If cancer-related lymphoedema, approval for participation in study from oncological specialist (patient participation has to be discussed during Multidisciplinary Oncological Consult); approval if:

• estimated cancer-related survival is ≥3 years
• oncological safety is guaranteed: for instance, time interval since radiotherapy/ chemotherapy is ≥3 months
• Lymphoedema stage 1 to 2b
• Objective diagnosis of lymphoedema: ≥ 5% volume difference OR ≥ 2 minor/ 1 major criteria on lymphoscintigraphy OR presence of IndoCyanineGreen (ICG) dermal backflow
• Score on Lymph-ICF questionnaire at screening: ≥ 25 / 100 (= moderate level of problems in functioning related to the development of lymphoedema)
• History of at least 6 months of decongestive lymphatic therapy (DLT) until minimal pitting
• Age ≥ 18 years

Exclusion criteria

• Participants with history of liposuction, lymphovenous anastomosis, lymph node transfer
• Pregnant participants
• Severe obese participants: BMI>35
• Estimated cancer-related survival is <3 years and oncological safety is not guaranteed (e.g. interval since radiotherapy/ chemotherapy is <3 months)
• In case of lower limb lymphoedema: presence of chronic venous insufficiency C4, C5, C6; deep venous thrombosis; post-thrombotic syndrome
• Allergy for ICG, iodine, penicillin and sulphonamides; increased activity of thyroid gland; benign tumour in thyroid; heparin use and severe renal insufficiency

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Belgium · 3 centers

• Ghent University Hospital — Ghent
• University Hospitals of Leuven, center for lymphedema — Leuven
• CHU-UCL Mont-Godinne — Namur

Publications

• Devoogdt N, De Vrieze T, Heroes AK, Bechter-Hugl B, Fieuws S, Godderis L, Segers K, Maleux G, Deltombe T, Frippiat J, Servaes M, Berners A, Fosseprez P, Krug B, Kayser F, Falticeanu A, Randon C, Monten C, Van Landuyt K, De Pypere B, Degraeve L, Decorte T, De Schryver M, Van Besien V, Devos D, Suominen S, Ayala JM, Pons G, Fourneau I, Thomis S. SurLym trial: study protocol for a multicentre pragmat PMID 38729754

Identifiers

NCT: NCT05064176 · KCE19-1245

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗