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NCT Number: NCT05890677

The LYMPH Trial - Microsurgical Versus Conservative Treatment of Chronic Breast Cancer Associated Lymphedema

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)

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Key information

Conditions

Lymphedema, Breast Cancer Breast Cancer Lymphedema Hemic and Lymphatic Diseases Lymphatic Diseases Lymphedema Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Clinics St.Pölten, Sankt Pölten, Lower Austria, Austria

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Surgical intervention

Procedure

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 Therapy

Procedure

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.

Primary outcomes

  1. Change in Quality of Life Questionnaire (Lymph-ICF-UL)

    Time frame: two time assessment at baseline and 15 month after randomization

    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.

Secondary outcomes

  1. Change in Quality of Life Questionnaire (Lymph-ICF-UL)

    Time frame: 13 time assessment up to 10 years after randomization

    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.

  2. Change in Quality of Life Questionnaire (LYMPH-Q)

    Time frame: 15 time assessment up to 10 years after randomization

    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.

  3. Change in Quality of Life Questionnaire (EuroQol EQ-5D-5L)

    Time frame: 15 time assessment up to 10 years after randomization

    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.

  4. Change in Pain score (visual analog scale)

    Time frame: 7 time assessment up to 2 years after randomization

    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.

  5. Assessment of (serious) adverse events

    Time frame: 7 time assessment up to 2 years after randomization

    Safety is assessed via a rigorous and detailed examination of (serious) adverse events.

  6. Assessment of surgical complications

    Time frame: 7 time assessment up to 2 years after randomization

    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.

  7. Assessment of lymphangitic events (erysipelas)

    Time frame: 7 time assessment up to 2 years after randomization

    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.

  8. Assessment of arm volume

    Time frame: 15 time assessment up to 10 years after randomization

    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.

  9. Assessment of the frequency of lymphatic drainage

    Time frame: 15 time assessment up to 10 years after randomization

    The frequency of lymphatic drainage before the start of the study and between the study's follow-up visits is assessed.

  10. Assessment of the burden on patients

    Time frame: 9 time assessment up to 10 years after randomization

    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.

  11. Assessment of the economics (for Switzerland)

    Time frame: 9 time assessment up to 10 years after randomization

    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 .

Study contacts

Contact information is provided by the study sponsor or research team.

Elisabeth Kappos, Prof. Dr.

CONTACT

[email protected]

+41 61 328 62 54

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Collaborators

  • Krebsforschung Schweiz, Bern, Switzerland
  • Rising Tide Foundation
  • Swiss National Science Foundation

Registry information

Official study 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

Acronym: LYMPH

Important dates

Study start
2023
Primary completion
2027
Study completion
2036
First posted
Jun 6, 2023
Registry last updated
Jun 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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