The LYMPH Trial - Microsurgical Versus Conservative Treatment of Chronic Breast Cancer Associated Lymphedema
LYMPH
The LYMPH Trial - Comparing Microsurgical With Conservative Treatment of Chronic Breast Cancer Associated Lymphedema: Study Protocol of a Pragmatic Randomized International Multicentre Superiority Trial
1 other identifier
interventional
280
15 countries
35
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Jul 2023
Longer than P75 for not_applicable
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 23, 2023
CompletedFirst Posted
Study publicly available on registry
June 6, 2023
CompletedStudy Start
First participant enrolled
July 14, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2036
November 14, 2025
November 1, 2025
4.1 years
May 23, 2023
November 13, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in Quality of Life Questionnaire (Lymph-ICF-UL)
The LYMPH-ICF-UL-Questionnaire (Lymphedema Functioning Disability and health questionnaire for upper limb lymphedema) is a widely used, rigorously developed, and validated patient-reported outcome (PRO) instrument for chronic breast cancer-related lymphedema. It assesses the impairments in function, activity limitations and participation restrictions of patients with upper limb lymphedema (LE). Consisting of 29 items (questions) across five different domains, each item is scored on a VAS (visual analog scale) ranging from 0 to 10. The total score on the LYMPH-ICF is equal to the sum of the item scores divided by the total number of answered items. A higher score on the Lymph-ICF indicates a greater impact on the functioning in daily life related to upper limb LE. This questionnaire helps determine if lymphatic surgery improves quality of life and patient satisfaction compared to conservative therapy.
two time assessment at baseline and 15 month after randomization
Secondary Outcomes (11)
Change in Quality of Life Questionnaire (Lymph-ICF-UL)
13 time assessment up to 10 years after randomization
Change in Quality of Life Questionnaire (LYMPH-Q)
15 time assessment up to 10 years after randomization
Change in Quality of Life Questionnaire (EuroQol EQ-5D-5L)
15 time assessment up to 10 years after randomization
Change in Pain score (visual analog scale)
7 time assessment up to 2 years after randomization
Assessment of (serious) adverse events
7 time assessment up to 2 years after randomization
- +6 more secondary outcomes
Study Arms (2)
Group A : Surgical Group
EXPERIMENTALAccording to the pragmatic study design, neither the diagnostic workup nor the surgery will be standardized in order to offer surgeons considerable leeway on how to perform lymphatic surgery, which resembles the flexibility in usual care. The key aspects of the preoperative workup and the surgery including the number of LVAs (Lymphovenous Anastomosis), harvesting of lymph nodes ("donor site"), time of surgery, and practical details will be registered.
Group B: Conservative Complex Physical Decongestion Therapy (control group)
ACTIVE COMPARATORCDT (Conservative Complex Physical Decongestion Therapy) will be performed as in usual care, following the pragmatic study design. The key aspects like frequency of lymphatic drainage, time when lymphatic drainage is performed and time and class of compressive garments are used will be documented. CDT incorporates two stages of treatment. The first treatment phase (intensive phase) entails skincare, MLD (manual lymphatic drainage), exercises aimed at improvement of mobility/range of motion in the shoulder, elbow or wrist joints, and compression therapy through bandaging. Most patients undergo this phase shortly after the diagnosis of LE. CDT in the second phase (maintenance phase) aims to maintain the achieved limb volume/ circumference reduction through compression with therapeutic elastic compression garment for the arm. Skincare, mobility exercises and MLD is continued in this phase if needed
Interventions
LVA (Lymphovenous Anastomosis) and VLNT (Vascularised Lymph Node Transfer) are two advanced microsurgical techniques that are increasingly implemented in clinical practice in specialized centers and that are already carried out after health insurance application according to local standard of care. They have been studied in their respective mode of action as well as in their effectiveness in treating chronic BCRL (Breast Cancer-Related Lymphedema) in a multitude of mostly observational and single center studies with highly encouraging results. Patients in the interventional arm A will receive surgery with one of the two approaches or a combination of both, in a one or two-stage method, at the discretion of the treating surgeon. Depending on local standards one or both of the above might be combined with liposuction to the affected arm in a one or two-stage approach as well.
Patients randomized to the control arm will receive CDT (Conservative Complex Physical Decongestion Therapy), which currently is considered as the best available standard of care. For this, patients will be referred to one of the dedicated LE (physical/skin) therapy clinics, if not already treated by one, according to their place of residence for continuation of standard conservative therapy. Recommendations to the procedures and treatment frequency of the conservative therapy will be made, but CDT will be done at the discretion of the treating physiotherapist.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Hospital, Basel, Switzerlandlead
- Swiss National Science Foundationcollaborator
- Rising Tide Foundationcollaborator
- Krebsforschung Schweiz, Bern, Switzerlandcollaborator
Study Sites (35)
Yale School of Medicine
New Haven, Connecticut, 06510, United States
Harvard Medical School
Boston, Massachusetts, 02115, United States
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110, United States
Mayo Clinic
Rochester, New York, 55905, United States
Krankenhaus Göttlicher Heiland GmbH
Vienna, A-1170, Austria
Brussels University Hospital
Brussels, Jette, 1090, Belgium
University of Ghent
Ghent, 9000, Belgium
Hospital Erasto Gaertner
Paraná, Curitiba, 80730-001, Brazil
McGill University, Royal Victoria Hospital
Montreal, QC H4A 3J1, Canada
University of British Columbia, Gordon and Leslie Diamond Health Care Centre
Vancouver, BC V5Z 1M9, Canada
BG Universitätsklinikum Bergmannsheil Bochum
Bochum, 44789, Germany
Sana Kliniken Düsseldorf
Düsseldorf, 40593, Germany
Uniklinikum Erlangen
Erlangen, 91054, Germany
KEM Evang. Kliniken Essen-Mitte
Essen, 45136, Germany
BG Klinik Frankfurt am Main
Frankfurt, 60389, Germany
Universitätsklinikum Freiburg, Klinik für Plastische und Handchirurgie
Freiburg im Breisgau, 79106, Germany
BG Klinik Ludwigshafen
Ludwigshafen am Rhein, 67071, Germany
Klinikum Nürnberg
Nuremberg, 90419, Germany
Caritas Krankenhaus St. Josef/ Uniklinik Regensburg
Regensburg, 93053, Germany
Papageorgiou Hospital of Thessaloniki
Thessaloniki, 55133, Greece
Rambam Health Clinic, ISR
Haifa, 3109601, Israel
Policlinico Tor Vergata: Fondazione PTV
Rome, 00133, Italy
Policlinico Universitario Fondazione Agostino Gemelli
Rome, 00168, Italy
Maastricht University Medical Center
Maastricht, 6202, Netherlands
Institute of Oncology ''Prof. Dr. Ion Chiricuță'' of Cluj-Napoca
Cluj-Napoca, 400015, Romania
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025, Spain
Karolinska Institutet, K1 Molekylär medicin och kirurgi
Stockholm, 17176, Sweden
Department of Plastic and Reconstructive Surgery Uppsala University Hospital
Uppsala, 751 85, Sweden
Kantonsspital Aarau
Aarau, 5001, Switzerland
University Hospital Basel
Basel, 4031, Switzerland
Hôpitaux Universitaires de Genève
Geneva, 1205, Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, 1011, Switzerland
Kantonsspital Winterthur
Winterthur, 8401, Switzerland
Klinik für Plastische, Rekonstruktive, Aesthetische und Handchirurgie
Zurich, 8091, Switzerland
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 833, Taiwan
Related Publications (1)
Kappos EA, Haas Y, Schulz A, Peters F, Savanthrapadian S, Stoffel J, Katapodi MC, Mucklow R, Kaiser B, Haumer A, Etter S, Cattaneo M, Staub D, Ribi K, Shaw J, Handschin TM, Eisenhardt S, Visconti G, Franceschini G, Scardina L, Longo B, Vetter M, Zaman K, Plock JA, Scaglioni M, Gonzalez EG, Quildrian SD, Felmerer G, Mehrara BJ, Ayala JM, Pons G, Kalbermatten DF, Sacks JM, Halle M, Muntean MV, Taylor EM, Mani M, Jung FJ, di Summa PG, Demiri E, Dionyssiou D, Groth AK, Heine N, Vorstenborsch J, Isaac KV, Qiu SS, Engels PE, Serre A, Eberhardt AL, Ebner S, Schwenkglenks M, Stoel Y, Leo C, Horch RE, Blondeel P, Behr B, Kneser U, Prantl L, Boll DT, Granziera C, Hemkens L, Lindenblatt N, Haug M, Schaefer DJ, Hirche C, Pusic AL, Seidenstuecker K, Harder Y, Weber W. The LYMPH trial: comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema - study protocol of a pragmatic randomised international multicentre superiority trial. BMJ Open. 2025 Feb 17;15(2):e090662. doi: 10.1136/bmjopen-2024-090662.
PMID: 39961719DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elisabeth Kappos, Prof. Dr.
University Hospital, Basel, Switzerland
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 23, 2023
First Posted
June 6, 2023
Study Start
July 14, 2023
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
June 1, 2036
Last Updated
November 14, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories following FAIR (Findability, Accessibility, Interoperability and Reuse) principles. The DKF of the University of Basel will act as an independent Data Access Committee, storing the data at time of publication on secure servers, maintained and backed-up by the IT-department of the University Hospital Basel. Researchers can request data reuse by submitting a project synopsis via dkf.unibas.ch/contact. Study results will be published in peer-reviewed journals following the Consolidated Standards of Reporting Trials (CONSORT) standards for randomized controlled trials (RCTs) and good publication practice, regardless of outcomes. Authorship for future publications will be based on contributions. An annual safety report is submitted to the local Ethics Committee by the Sponsor-Investigator according to national regulations.