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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05890677
Other study ID # 2023-00733; mu21kappos
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date July 14, 2023
Est. completion date December 2035

Study information

Verified date June 2024
Source University Hospital, Basel, Switzerland
Contact Elisabeth Kappos, PD Dr. med.
Phone +41 61 328 62 54
Email elisabeth.kappos@usb.ch
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 patients with chronic lymphedema (LE)


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 280
Est. completion date December 2035
Est. primary completion date June 2035
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Written informed consent. - Patients = 18 years of age with prior treatment of breast cancer. - At least one of the following prior breast cancer treatments: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), radiotherapy (RT) of chest wall or axilla or breast cancer surgery. - Clinical diagnosis of chronic BCRL as defined by the ISL (inter-limb difference of >10% in volume or excess volume between the affected and non-affected limbs present for more than 3 months). - Minimum of 3 months CDT. - Ability to complete the QoL questionnaires. Exclusion Criteria: - No indication for lymphatic surgery according to clinical judgment of the treating surgeon (individual reasons will be specifically documented). - Primary congenital LE or non-breast cancer-related LE. - Need for immediate LE surgery according to clinical judgement by a specialist due to far progressed LE stage.

Study Design


Intervention

Procedure:
Surgical Intervention
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
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.

Locations

Country Name City State
Argentina Universidad de Buenos Aires, Instituto de Oncología Ángel H. Roffo Buenos Aires
Austria Klinikum Klagenfurt Klagenfurt
Belgium University of Ghent Gent
Brazil Hospital Erasto Gaertner Paraná Curitiba
Canada McGill University, Royal Victoria Hospital Montreal
Canada University of British Columbia, Gordon and Leslie Diamond Health Care Centre Vancouver
Germany Sana Kliniken Düsseldorf Düsseldorf
Germany Uniklinikum Erlangen Erlangen
Germany KEM Evang. Kliniken Essen-Mitte Essen
Germany BG Klinik Frankfurt am Main Frankfurt
Germany Universitätsklinikum Freiburg, Klinik für Plastische und Handchirurgie Freiburg im Breisgau
Germany Universitätsklinikum Göttingen Göttingen
Germany BG Klinik Ludwigshafen Ludwigshafen am Rhein
Germany Caritas Krankenhaus St. Josef/ Uniklinik Regensburg Regensburg
Greece Papageorgiou Hospital of Thessaloniki Thessaloníki
Italy Plastic and Reconstructive Surgery at Department of Surgical Science Rome
Italy Policlinic Gemelli, Operational Unit of Plastic Surgery Rome
Netherlands Maastricht University Medical Center Maastricht
Romania Institute of Oncology ''Prof. Dr. Ion Chiricu?a'' of Cluj-Napoca Cluj-Napoca
Spain Hospital de la Santa Creu i Sant Pau Barcelona
Sweden Karolinska Institutet, K1 Molekylär medicin och kirurgi Stockholm
Sweden Department of Plastic and Reconstructive Surgery Uppsala University Hospital Uppsala
Switzerland Kantonsspital Aarau Aarau
Switzerland University Hospital Basel Basel
Switzerland Hôpitaux Universitaires de Genève Genève
Switzerland Centre Hospitalier Universitaire Vaudois Lausanne
Switzerland Ospedale Regionale di Lugano Viganello Lugano
Switzerland Kantonsspital Winterthur Winterthur
Switzerland Klinik für Plastische, Rekonstruktive, Aesthetische und Handchirurgie Zürich
United States Harvard Medical School Boston Massachusetts
United States Washington University School of Medicine in St. Louis Saint Louis Missouri

Sponsors (4)

Lead Sponsor Collaborator
University Hospital, Basel, Switzerland Krebsforschung Schweiz, Bern, Switzerland, Rising Tide Foundation, Swiss National Science Foundation

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  Germany,  Greece,  Italy,  Netherlands,  Romania,  Spain,  Sweden,  Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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. 13 time assessment up to 10 years after randomization
Secondary 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.
15 time assessment up to 10 years after randomization
Secondary 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.
15 time assessment up to 10 years after randomization
Secondary 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.
7 time assessment up to 2 years after randomization
Secondary Assessment of (serious) adverse events Safety is assessed via a rigorous and detailed examination of (serious) adverse events. 7 time assessment up to 2 years after randomization
Secondary 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.
7 time assessment up to 2 years after randomization
Secondary 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. 7 time assessment up to 2 years after randomization
Secondary 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. 15 time assessment up to 10 years after randomization
Secondary 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. 15 time assessment up to 10 years after randomization
Secondary 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. 9 time assessment up to 10 years after randomization
Secondary 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 .
9 time assessment up to 10 years after randomization
See also
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