Lymphedema, Breast CancerLYMPHNCT05890677
The LYMPH Trial - Microsurgical Versus Conservative Treatment of Chronic Breast Cancer Associated Lymphedema
A study testing Surgical Intervention and Conservative Complex Physical Decongestion Therapy in people with Lymphedema, Breast Cancer, run by University Hospital, Basel, Switzerland at 36 sites in 15 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphedema, Breast Cancer
- What is being tested?
- Surgical Intervention and Conservative Complex Physical Decongestion Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 36 sitesin 15 countries
- Study dates
- 14 Jul 2023to Jun 2036
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
36 sites in 15 countries. Contact the study team or a site near you to ask about taking part.
36 sites in 15 countries
Germany9 sites, 9 recruiting
- Recruiting
BG Universitätsklinikum Bergmannsheil Bochum
Bochum, 44789
Christoph Wallner, PD Dr. med., M.Sc., MHBA, christoph.wallner@bergmannsheil.de
- Recruiting
Sana Kliniken Düsseldorf
Düsseldorf, 40593
Katrin Seidenstücker, Dr., +49 211 2800 1990, katrin.seidenstuecker@sana.de
- Recruiting
Uniklinikum Erlangen
Erlangen, 91054
Raymund Horch, Prof. Dr., Raymund.Horch@uk-erlangen.de
- Recruiting
KEM Evang. Kliniken Essen-Mitte
Essen, 45136
Björn Behr, Prof. Dr. med., +49 234 302 7152, transchirurgie-zentrum@kem-med.com
+49 201 174 29006, bjorn.behr@rub.de
- Recruiting
BG Klinik Frankfurt am Main
Frankfurt, 60389
Christoph Hirche, Prof. Dr. med., +49 69 475 23 23, ulrich.kneser@bgu-ludwigshafen.de
- Recruiting
Universitätsklinikum Freiburg, Klinik für Plastische und Handchirurgie
Freiburg im Breisgau, 79106
Steffen Eisenhardt, Prof. Dr. med., +49 761 270 28170, steffen.eisenhardt@uniklinik-freiburg.de
bianca.kremer@uniklinik-freiburg.de
- Recruiting
BG Klinik Ludwigshafen
Ludwigshafen am Rhein, 67071
Ulrich Kneser, Prof. Dr. med., +49 621 681 023 28, ulrich.kneser@bgu-ludwigshafen.de
- Recruiting
Klinikum Nürnberg
Nuremberg, 90419
Denis Ehrl, MD, denis.ehrl@klinikum-nuernberg.de
Denis Ehrl, MD
- Recruiting
Caritas Krankenhaus St. Josef/ Uniklinik Regensburg
Regensburg, 93053
Lukas Prantl, Prof. Dr. med., +49 941 944 6763, Lukas.Prantl@klinik.uni-regensburg.de
Norbert Heine, Dr. med.
Switzerland6 sites, 6 recruiting
- Recruiting
Kantonsspital Aarau
Aarau, 5001
Jan Plock, Prof. Dr. med., +41 62 838 47 31, plastischechirurgie@ksa.ch
- Recruiting
University Hospital Basel
Basel, Basel, 4031
Elisabeth Kappos, Prof. Dr., +41 61 328 62 54, elisabeth.kappos@usb.ch
Elisabeth Kappos, Prof. Dr.
- Recruiting
Hôpitaux Universitaires de Genève
Geneva, 1205
Daniel Kalbermatten, Prof. Dr. med., +41 22 372 80 12, daniel.kalbermatten@hcuge.ch
- Recruiting
Centre Hospitalier Universitaire Vaudois
Lausanne, Lausanne, 1011
Pietro di Summa, PD Dr. med., +41 21 314 25 25, pietro.di-summa@chuv.ch
- Recruiting
Kantonsspital Winterthur
Winterthur, 8401
Florian Jung, Dr. med., +41 52 266 24 08, Florian.Jung@ksw.ch
- Recruiting
Klinik für Plastische, Rekonstruktive, Aesthetische und Handchirurgie
Zurich, 8091
Nicole Lindenblatt, Prof. Dr. med., +41 44 255 11 11, nicole.lindenblatt@usz.ch
United States4 sites, 3 recruiting
- Recruiting
Harvard Medical School
Boston, Massachusetts, 02115
Andrea Pusic, Prof. Dr. med., +16 17 732 53 61, apusic@bwh.harvard.edu
Erin Taylor, Dr. med.
- Withdrawn
Yale School of Medicine
New Haven, Connecticut, 06510
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Vahe Fahradyan, M. D., (507)284-0850
Vahe Fahradyan, M. D.
- Recruiting
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
Justin M. Sacks, Prof. Dr., +1 314-454-4894, jmsacks@wustl.edu
Austria2 sites, 2 recruiting
- Recruiting
University Clinics St.Pölten
Sankt Pölten, Lower Austria
Klaus Schrögendorfer, 0613285402, lymph.trial@usb.ch
Christina Glisic
- Recruiting
Krankenhaus Göttlicher Heiland GmbH
Vienna, State of Vienna, A-1170
Tina Deutinger, MD, PhD
Tina Deutinger, MD
Belgium2 sites, 2 recruiting
- Recruiting
Brussels University Hospital
Brussels, Jette, 1090
Mustapha/Alexandru Hamdi/Nistor, MD
Mustapha Hamdi, MD
- Recruiting
University of Ghent
Ghent, 9000
Phillip Blondeel, Prof. Dr., Phillip.Blondeel@ugent.be
Canada2 sites, 2 recruiting
- Recruiting
McGill University, Royal Victoria Hospital
Montreal, QC H4A 3J1
Josh Vorstenbosch, MD PhD FRCSC, +1(514)934-1934 x 35194, joshua.vorstenbosch@mcgill.ca
Anna Towers, Dr.
- Recruiting
University of British Columbia, Gordon and Leslie Diamond Health Care Centre
Vancouver, BC V5Z 1M9
Kathryn V. Isaac, Asst. Prof. Dr., +1 604-336-9488, kathryn.isaac@ubc.ca
Italy2 sites, 2 recruiting
- Recruiting
Policlinico Tor Vergata: Fondazione PTV
Rome, 00133
Benedetto Longo, Dr. med., +39 6 44291148, benedetto.longo@uniroma2.it
info@benedettolongo.com
- Recruiting
Policlinico Universitario Fondazione Agostino Gemelli
Rome, 00168
Giuseppe Visconti, Dr. med., +39 06 30151, giuseppe.visconti@policlinicogemelli.it
Sweden2 sites, 2 recruiting
- Recruiting
Karolinska Institutet, K1 Molekylär medicin och kirurgi
Stockholm, 17176
Martin Halle, Dr. med., +46 8 123 708 46, martin.halle@ki.se
- Recruiting
Department of Plastic and Reconstructive Surgery Uppsala University Hospital
Uppsala, 751 85
Maria Mani, Dr. med., Maria.Mani@surgsci.uu.se
Greece1 site, 1 recruiting
- Recruiting
Papageorgiou Hospital of Thessaloniki
Thessaloniki, 55133
Efterpi Demiri, Prof. Dr. med., +30 231 332 38 38, demirie@auth.gr
Dimitrios Dionysiou, Dr. med.
Israel1 site, 1 recruiting
- Not yet recruiting
Rambam Health Clinic, ISR
Haifa, 3109601
Assaf Zeltzer, a_zeltzer@rambam.health.gov.il
Assaf Zeltzer
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht University Medical Center
Maastricht, 6202
Shao Shan Qiu, Dr., +31(0)43-3877481, shanshan.qiushao@mumc.nl
Romania1 site, 1 recruiting
- Recruiting
Institute of Oncology ''Prof. Dr. Ion Chiricuță'' of Cluj-Napoca
Cluj-Napoca, 400015
Maximilian Vlad Muntean, Dr. med., +40 730085422, maximilian.muntean@gmail.com
Spain1 site, 1 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Gemma Pons, Dr., +34 935565693, GPonsP@santpau.cat
Taiwan1 site, 1 recruiting
- Recruiting
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, Taiwan, 833
Johnson Chia-Shen Yang, MD
Johnson Chia-Shen Yang, MD
About this study
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
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)
Read the 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.
- Conditions
- Lymphedema, Breast Cancer
- Being tested
- Surgical Intervention, Conservative Complex Physical Decongestion Therapy
- Keywords
- lymphatic surgery, breast cancer related lymphedema, sentinel lymph node biopsy, axillary lymph node dissection, manual lymphatic drainage, conservative complex physical decongestion therapy
- Medical subject headings
- Breast Cancer Lymphedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical InterventionProcedure or surgery
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.
Conservative Complex Physical Decongestion TherapyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Group A : Surgical Group | Experimental | According 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. Receives: Procedure: Surgical Intervention |
| Group B: Conservative Complex Physical Decongestion Therapy (control group) | Active comparator | CDT (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 Receives: Procedure: Conservative Complex Physical Decongestion Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: two time assessment at baseline and 15 month after randomization
Secondary outcomes (11)
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.
Measured: 13 time assessment up to 10 years after randomization
Change in Quality of Life Questionnaire (LYMPH-Q)
The Lymph-Q Upper Extremity Module is a new PROM (patient-reported outcome measure) developed to assess patient reported outcomes of BCRL in a concept-driven approach. The complete questionnaire contains 68 questions covering the patient-relevant topics Health-related quality of life (arm appearance, arm function, arm symptoms, psychological), experience of care (information), and treatment (arm sleeve).
The questionnaire is used to determine whether lymphatic surgery provides better quality of life and patient satisfaction compared to conservative therapy.
Measured: 15 time assessment up to 10 years after randomization
Change in Quality of Life Questionnaire (EuroQol EQ-5D-5L)
The 5-level EQ-5D version (EQ-5D-5L) consists of the EQ-5D descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions (5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems) resulting in a 1-digit number that expresses the level for that dimension. The digits for each dimension can be combined into a 5-digit number that describes the patient's health state.
The questionnaire is used to determine whether lymphatic surgery provides better quality of life and patient satisfaction compared to conservative therapy.
Measured: 15 time assessment up to 10 years after randomization
Change in Pain score (visual analog scale)
The pain score consists of a VAS (visual analog scale) ranging from 0 (i.e. no pain) to 10 (i.e. worst pain). The VAS was published by the Yale University.
It is used to determine whether lymphatic surgery provides better quality of life and patient satisfaction compared to conservative therapy.
Measured: 7 time assessment up to 2 years after randomization
Assessment of (serious) adverse events
Safety is assessed via a rigorous and detailed examination of (serious) adverse events.
Measured: 7 time assessment up to 2 years after randomization
Assessment of surgical complications
For the surgery group only, safety is assessed via a rigorous and detailed examination of complications of surgery. Grading is according to the modified classification of Clavien-Dindo, categorizing them into five levels ranging from minor deviations to life-threatening events.
The assessment will cover both surgical stages in case of two-staged lymphedema (LE) surgery.
Measured: 7 time assessment up to 2 years after randomization
Assessment of lymphangitic events (erysipelas)
The frequency of lymphangitic events (erysipelas) is closely monitored. Lymphangitic events are defined as skin infections at the lymphedema site(s) which can be treated with oral or intravenous antibiotics. The type of antibiotic given, the application form, type of hospital stay and necessity of a surgery will be assessed.
Measured: 7 time assessment up to 2 years after randomization
Assessment of arm volume
Arm volume is determined by measuring the circumference of each arm at 10 cm intervals from the wrist to the axilla. The volume of each arm segment is calculated using a truncated cone model, and percentage edema volume is derived from the volume difference between the affected and unaffected arms. Both relative (relative to the unaffected arm) and absolute (volume reduction of the affected arm at the next measurement) volume change are calculated, corrected for BMI and differences between dominant and non-dominant arms.
Measured: 15 time assessment up to 10 years after randomization
Assessment of the frequency of lymphatic drainage
The frequency of lymphatic drainage before the start of the study and between the study's follow-up visits is assessed.
Measured: 15 time assessment up to 10 years after randomization
Assessment of the burden on patients
To assess the burden on patients, information regarding the total number of operative procedures, length of hospital stays, number of outpatient visits, and absence from work within two years after randomization and during the extended follow-up is collected.
Measured: 9 time assessment up to 10 years after randomization
Assessment of the economics (for Switzerland)
To perform an economic evaluation, information regarding the condition-related medical resource use, healthcare costs, indirect costs, productivity losses, and incremental cost-effectiveness (quality-adjusted life-years) is collected.
The information is based on the responses to the EQ-5D-5L questionnaire, the questions asked under burden on patients, and on other medical resource information recorded in the trial primarily for clinical purposes, at the respective visits. In addition, direct extraction of breast cancer-related lymphedema-related in- and outpatient costs, and corresponding key resource use parameters, are collected from the hospital administration systems of the participating Swiss sites, once at the 2 year follow-up visit .
Measured: 9 time assessment up to 10 years after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2023
- Study start14 Jul 2023
- Primary completionSep 2027 (estimated)
- Study completionJun 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphedema, Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pragmatic, randomized, international, multicenter superiority trial
- Masking
- None (open label)
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation, Rising Tide Foundation, Krebsforschung Schweiz, Bern, Switzerland
- Responsible party
- Sponsor
- Investigators
- Elisabeth Kappos, Prof. Dr., Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05890677
- Sponsor's protocol ID
- 2023-00733; mu21kappos
- Other IDs
- 2023
- Acronym
- LYMPH
- Status last verified
- Oct 2026
- First submitted
- 23 May 2023
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39961719