Clinical trial NCT02790021: Microsurgical Treatment of Breast Cancer-related Lymphedema by Lymphaticovenous Anastomosis
Official title: Improving the Quality of Life of Patients With Breast Cancer-related Lymphedema by Lymphaticovenous Anastomosis (LVA): A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lymphedema
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2016-06-03
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Research question: Is lymphaticovenous anastomosis (LVA) for the treatment of breast cancer-related lymphedema of the arm (BCRL) more effective and cost-effective compared to standard conservative treatment? Hypothesis: LVA improves the health-related quality of life of patients who developed BCRL after breast cancer treatment and is cost-effective compared to conservative treatment. Study design: A multicenter randomised controlled trial (RCT) consisting of two treatment groups: conservative treatment (group A) and LVA (group B). The study is conducted in Maastricht University Medical Center, Radboud University Medical Center, Zuyderland Medical Center and Canisius-Wilhelmina Hospital. Study population: Women over 18 years old who underwent (axillary) treatment for breast cancer presenting with early stage lymphedema of the arm for which they received at least three months conservative treatment Intervention: LVA involves anastomosing lymphatic vessels to small veins to bypass obstructions in the lymphatic system.

Usual care: Complex decongestive therapy (CDT) which includes skin care, manual lymphatic drainage, and compression therapy. Outcome measures: The primary outcome is health-related quality of life after 12 months follow-up measured with the Lymph-ICF questionnaire. Secondary outcomes are (in)direct costs, QALYs, cost-effectiveness ratio, the discontinuation rate of conservative treatment, and excess limb volume. Sample size: A total of 120 patients will be included and randomised in two groups of 60 patients each.

Cost-effectiveness analysis: A trial-based economic evaluation is performed from the societal perspective to determine the cost-effectiveness, expressed in an incremental cost-effectiveness ratio (ICER) (i.e. cost per QALY gained), of LVA compared to CDT. Direct and indirect cost data is collected on the patient-level. The difference in QALYs is assessed with the EQ-5D-5L questionnaire. A Budget Impact Analysis (BIA) will be performed to analyse the financial consequences related to implementing LVA. Time schedule: Patient inclusion will take maximally 21 months. With a follow-up of 24 months, the total study period will be 48 months. The last three months are used for data analysis. Outcome assessment is at inclusion (before randomisation) and 3, 6, 12, 18, and 24 months later.


Eligibility criteria: Inclusion Criteria:

* Women over 18 years old
* Treated for early stage breast cancer and who underwent an sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND) or axillary radiotherapy
* Early stage lymphedema of the arm (ISL classification stage I/IIa; pitting edema without fibrosis) with viable lymphatic vessels as determined by indocyanin green (ICG) lymphography
* Already received at least three months of complex decongestive therapy (CDT) prior to inclusion
* Primary breast cancer
* Unilateral lymphedema
* Informed consent

Exclusion Criteria:

* Male sex
* Late stage lymphedema of the arm (ISL classification IIb/III lymphedema) with evident fat deposition and/or fibrosis
* History of earlier lymph reconstruction efforts
* Recurrent breast cancer
* Distant breast cancer metastases
* Bilateral lymphedema
* Primary congenital lymphedema
* Non-viable lymphatic system as determined by ICG lymphography

Primary outcomes:
measure: Health-related quality of life: Lymph-ICF questionnaire
timeFrame: 12 months
Secondary outcomes:
measure: Cost-effectiveness of LVA compared to complex decongestive therapy
timeFrame: 24 months
measure: Excess limb volume
timeFrame: 24 months
measure: Discontinuation rate conservative therapy
timeFrame: 24 months
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Maastricht
country: Netherlands
facility: Yasmine Jonis
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center
name: René Van der Hulst, MD, PhD
role: STUDY_DIRECTOR
affiliation: Maastricht University Medical Center
name: Shan Shan Qiu Shao, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wolfs J, Beugels J, Kimman M, Piatkowski de Grzymala AA, Heuts E, Keuter X, Tielemans H, Ulrich D, van der Hulst R, Qiu SS. Improving the quality of life of patients with breast cancer-related lymphoedema by lymphaticovenous anastomosis (LVA): study protocol of a multicentre randomised controlled trial. BMJ Open. 2020 Jan 15;10(1):e035337. doi: 10.1136/bmjopen-2019-035337.