Clinical trial NCT05890677: The LYMPH Trial - Microsurgical Versus Conservative Treatment of Chronic Breast Cancer Associated Lymphedema
Official title: The LYMPH Trial - Comparing Microsurgical With Conservative Treatment of Chronic Breast Cancer Associated Lymphedema: Study Protocol of a Pragmatic Randomized International Multicentre Superiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lymphedema, Breast Cancer
Keywords: lymphatic surgery
breast cancer related lymphedema
sentinel lymph node biopsy
axillary lymph node dissection
manual lymphatic drainage
conservative complex physical decongestion therapy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: Rising Tide Foundation
name: Krebsforschung Schweiz, Bern, Switzerland
First posted: 2023-06-06
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic, randomized, international, multicenter superiority trial
Primary purpose: TREATMENT

Brief summary: The aim of this study is to test whether lymphatic surgery provides better QoL (assessed with the Lymph-ICF-UL, (Lymphedema Functioning Disability and health questionnaire for upper limb lymphedema)) 15 months after randomization (and therefore about one year after surgery) compared to conservative treatment only for patients with chronic lymphedema (LE)

Detailed description: To date, conservative complex physical decongestion therapy (CDT) is the gold standard for BCRL (breast cancer related lymphedema) and includes manual lymphatic drainage, local compression with bandages and garments, physical exercises and meticulous skin care. It is, however, too often ineffective to prevent stage progression in curing BCRL and purely symptomatic. Lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT) are two surgical techniques that, in contrast to CDT, are able to actually address the underlying causes and eventually restore the lymphatic drainage. LVA achieves this by creating numerous bypasses between lymphatic vessels and venules allowing the drainage of excessive fluid within the subcutaneous tissues into the venous system, while VLNT usually brings functioning lymph nodes to an area devoid of lymph nodes or with dysfunctional lymph nodes, thus enabling the spontaneous development of new lymphatic pathways. Both techniques have shown very promising results with low complication rates and improved Quality of Life (QoL) for the patients. However, no multicentric randomized controlled trial (RCT) has yet prospectively evaluated the superiority of these surgical techniques over CDT alone, limiting patient's access to most effective treatment available. Requests for cost reimbursement must still be submitted to insurance companies in most countries and are often rejected, thus delaying surgical treatment and resulting in prolonged suffering of affected patients. This is untenable seeing as affected patients suffer from a heavy physical, psychological and financial burden. This pragmatic, randomized, multicenter trial aims to establish a solid scientific basis assessing the superiority of surgical treatment over CDT alone.

Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Patients ≥ 18 years of age.
* Former diagnosis of breast cancer.
* Clinical diagnosis of chronic Breast Cancer-Related Lymphedema (BCRL) (persisting for more than 3 months) classified as ≥ Stage 1, according to ISL.
* Minimum of 3 months Conservative Complex Physical Decongestion Therapy.
* Ability to complete the QoL questionnaires.
* Willingness to undergo surgery.

Exclusion Criteria:

* No indication for lymphatic surgery according to clinical judgment of the treating surgeon (individual reasons will be specifically documented).
* Primary congenital Lymphedema or non-BCRL.
* Previous surgical BCRL treatment on the side intended for intervention.

Primary outcomes:
measure: Change in Quality of Life Questionnaire (Lymph-ICF-UL)
timeFrame: two time assessment at baseline and 15 month after randomization
Secondary outcomes:
measure: Change in Quality of Life Questionnaire (Lymph-ICF-UL)
timeFrame: 13 time assessment up to 10 years after randomization
measure: Change in Quality of Life Questionnaire (LYMPH-Q)
timeFrame: 15 time assessment up to 10 years after randomization
measure: Change in Quality of Life Questionnaire (EuroQol EQ-5D-5L)
timeFrame: 15 time assessment up to 10 years after randomization
measure: Change in Pain score (visual analog scale)
timeFrame: 7 time assessment up to 2 years after randomization
measure: Assessment of (serious) adverse events
timeFrame: 7 time assessment up to 2 years after randomization
measure: Assessment of surgical complications
timeFrame: 7 time assessment up to 2 years after randomization
measure: Assessment of lymphangitic events (erysipelas)
timeFrame: 7 time assessment up to 2 years after randomization
measure: Assessment of arm volume
timeFrame: 15 time assessment up to 10 years after randomization
measure: Assessment of the frequency of lymphatic drainage
timeFrame: 15 time assessment up to 10 years after randomization
measure: Assessment of the burden on patients
timeFrame: 9 time assessment up to 10 years after randomization
measure: Assessment of the economics (for Switzerland)
timeFrame: 9 time assessment up to 10 years after randomization
Other outcomes:
Locations:
city: Boston
country: United States
facility: Harvard Medical School
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Gent
country: Belgium
facility: University of Ghent
city: Paraná
country: Brazil
facility: Hospital Erasto Gaertner
state: Curitiba
city: Montreal
country: Canada
facility: McGill University, Royal Victoria Hospital
city: Vancouver
country: Canada
facility: University of British Columbia, Gordon and Leslie Diamond Health Care Centre
city: Bochum
country: Germany
facility: BG Universitätsklinikum Bergmannsheil Bochum
city: Düsseldorf
country: Germany
facility: Sana Kliniken Düsseldorf
city: Erlangen
country: Germany
facility: Uniklinikum Erlangen
city: Essen
country: Germany
facility: KEM Evang. Kliniken Essen-Mitte
city: Frankfurt
country: Germany
facility: BG Klinik Frankfurt am Main
city: Freiburg im Breisgau
country: Germany
facility: Universitätsklinikum Freiburg, Klinik für Plastische und Handchirurgie
city: Ludwigshafen am Rhein
country: Germany
facility: BG Klinik Ludwigshafen
city: Regensburg
country: Germany
facility: Caritas Krankenhaus St. Josef/ Uniklinik Regensburg
city: Thessaloníki
country: Greece
facility: Papageorgiou Hospital of Thessaloniki
city: Haifa
country: Israel
facility: Rambam Health Clinic, ISR
city: Rome
country: Italy
facility: Plastic and Reconstructive Surgery at Department of Surgical Science
city: Rome
country: Italy
facility: Policlinic Gemelli, Operational Unit of Plastic Surgery
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Cluj-Napoca
country: Romania
facility: Institute of Oncology ''Prof. Dr. Ion Chiricuță'' of Cluj-Napoca
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Stockholm
country: Sweden
facility: Karolinska Institutet, K1 Molekylär medicin och kirurgi
city: Uppsala
country: Sweden
facility: Department of Plastic and Reconstructive Surgery Uppsala University Hospital
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zürich
country: Switzerland
facility: Klinik für Plastische, Rekonstruktive, Aesthetische und Handchirurgie
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Elisabeth Kappos, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: