LymphedemaNCT02790021
Microsurgical Treatment of Breast Cancer-related Lymphedema by Lymphaticovenous Anastomosis
A study testing Lymphaticovenous anastomosis (LVA) in people with Lymphedema, run by Maastricht University Medical Center at 2 sites in Netherlands.
Trial summary
Research question: Is lymphaticovenous anastomosis (LVA) for the treatment of breast cancer-related lymphedema of the arm (BCRL) more effective and cost-effective compared to standard conservative treatment? Hypothesis: LVA improves the health-related quality of life of patients who developed BCRL after breast cancer… Read more about this study
- Who is it for?
- Ages 18 to 99 years, women only
- Conditions the study is for
- Lymphedema
- What is being tested?
- Lymphaticovenous anastomosis (LVA)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesNetherlands
- Study dates
- 1 Jan 2019to 7 Jan 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 99 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women over 18 years old
- Treated for early stage breast cancer and who underwent an sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND) or axillary radiotherapy
- Early stage lymphedema of the arm (ISL classification stage I/IIa; pitting edema without fibrosis) with viable lymphatic vessels as determined by indocyanin green (ICG) lymphography
- Already received at least three months of complex decongestive therapy (CDT) prior to inclusion
- Primary breast cancer
- Unilateral lymphedema
- Informed consent
Who cannot join
- Male sex
- Late stage lymphedema of the arm (ISL classification IIb/III lymphedema) with evident fat deposition and/or fibrosis
- History of earlier lymph reconstruction efforts
- Recurrent breast cancer
- Distant breast cancer metastases
- Bilateral lymphedema
- Primary congenital lymphedema
- Non-viable lymphatic system as determined by ICG lymphography
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Yasmine Jonis
Maastricht, Limburg, 6229 HX
Radboud University Medical Center
Nijmegen, Gelderland, 6526 GA
About this study
Official title: Improving the Quality of Life of Patients With Breast Cancer-related Lymphedema by Lymphaticovenous Anastomosis (LVA): A Randomized Controlled Trial
Research question: Is lymphaticovenous anastomosis (LVA) for the treatment of breast cancer-related lymphedema of the arm (BCRL) more effective and cost-effective compared to standard conservative treatment? Hypothesis: LVA improves the health-related quality of life of patients who developed BCRL after breast cancer treatment and is cost-effective compared to conservative treatment. Study design: A multicenter randomised controlled trial (RCT) consisting of two treatment groups: conservative treatment (group A) and LVA (group B). The study is conducted in Maastricht University Medical Center, Radboud University Medical Center, Zuyderland Medical Center and Canisius-Wilhelmina Hospital. Study population: Women over 18 years old who underwent (axillary) treatment for breast cancer presenting with early stage lymphedema of the arm for which they received at least three months conservative treatment Intervention: LVA involves anastomosing lymphatic vessels to small veins to bypass obstructions in the lymphatic system.
Usual care: Complex decongestive therapy (CDT) which includes skin care, manual lymphatic drainage, and compression therapy. Outcome measures: The primary outcome is health-related quality of life after 12 months follow-up measured with the Lymph-ICF questionnaire. Secondary outcomes are (in)direct costs, QALYs, cost-effectiveness ratio, the discontinuation rate of conservative treatment, and excess limb volume. Sample size: A total of 120 patients will be included and randomised in two groups of 60 patients each.
Cost-effectiveness analysis: A trial-based economic evaluation is performed from the societal perspective to determine the cost-effectiveness, expressed in an incremental cost-effectiveness ratio (ICER) (i.e. cost per QALY gained), of LVA compared to CDT. Direct and indirect cost data is collected on the patient-level. The difference in QALYs is assessed with the EQ-5D-5L questionnaire. A Budget Impact Analysis (BIA) will be performed to analyse the financial consequences related to implementing LVA. Time schedule: Patient inclusion will take maximally 21 months. With a follow-up of 24 months, the total study period will be 48 months. The last three months are used for data analysis. Outcome assessment is at inclusion (before randomisation) and 3, 6, 12, 18, and 24 months later.
- Conditions
- Lymphedema
- Being tested
- Lymphaticovenous anastomosis (LVA)
- Medical subject headings
- Lymphedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lymphaticovenous anastomosis (LVA)Procedure or surgery
Also called LVA
LVA is a minimally invasive procedure that can be performed under local anesthesia. Indocyanine green (ICG) lymphography is used to visualize the (obstructed) lymphatic vessels. When using the images as a guide, the lymphatic pathways and the sites for incisions for lymphaticovenous anastomoses are marked with a pen. The patient's limb is then prepared for surgery. Under a surgical microscope the lymphatic vessels are identified and viable lymphatic vessels are anastomosed to similarly sized adjacent recipient venules in the subdermal plane.
| Study group | Role | What they receive |
|---|---|---|
| Complex decongestive therapy | No intervention | Group A will continue complex decongestive therapy consisting of skin care, manual lymphatic drainage, and compression therapy using compression stockings. |
| Lymphaticovenous anastomosis (LVA) | Experimental | Group B will undergo an LVA procedure under local anesthesia in surgical daycare setting. Patients are not allowed to wear compression stockings or have decongestive therapy for four weeks after the surgery. Receives: Procedure: Lymphaticovenous anastomosis (LVA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Health-related quality of life: Lymph-ICF questionnaire
To assess the efficacy of the treatment on disease-related symptoms we will use the "Lymphedema Functioning, Disability and Health" (Lymph-ICF)" questionnaire. This disease-specific questionnaire assesses the impairments in function, activity limitations, and participation restrictions of patients with arm lymphedema. This is a validated questionnaire, based on 5 domains with 29 questions. Each of the 29 questions corresponds to a score between 0-100. The total score on the Lymph-ICF is equal to the sum of the scores on the questions divided by the total number of answered questions. A higher score on the Lymph-ICF indicates more problems with functioning related to arm lymphedema.
Measured: 12 months
Secondary outcomes (3)
Cost-effectiveness of LVA compared to complex decongestive therapy
A trial-based economic evaluation is performed to determine the cost-effectiveness of LVA compared to complex decongestive therapy from the societal perspective. Cost data is collected on the patient-level and includes health care related costs, costs to patient and family, and costs due to lost productivity. The primary outcome measure for the effects is the quality-adjusted life year (QALY). Cost-effectiveness is expressed in an incremental cost-effectiveness ratio (ICER) (i.e. cost per QALY gained). In addition, a Budget Impact Analysis (BIA) will be performed from a budget holder perspective.
Measured: 24 months
Excess limb volume
The relative arm volume is measured using the water displacement method (Bravometer), 3D volumetry, and circumference measurement. The volume of the affected arm is compared to the volume of the unaffected arm.
Measured: 24 months
Discontinuation rate conservative therapy
The number of patients who are able to discontinue conservative therapy, i.e. no longer have to wear compression stockings or no more visits to the therapist, will be registered.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2016 (estimated)
- Study start1 Jan 2019
- Primary completion7 Jan 2025
- Study completion7 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LymphedemaStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- 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
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Sponsor
- Investigators
- René Van der Hulst, MD, PhD, Study director, Maastricht University Medical CenterShan Shan Qiu Shao, MD, PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02790021
- Sponsor's protocol ID
- NL67059.068.18
- Status last verified
- May 2025
- First submitted
- 11 May 2016
- Last updated
- 19 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kleeven A, Jonis YMJ, Currie O, Wolfs J, Kimman M, Tielemans H, van der Hulst RRWJ, Hummelink S, Qiu SS. Economic evaluation of lymphaticovenous anastomosis versus conservative therapy for breast cancer-related lymphoedema: secondary outcome analysis of a randomized clinical trial. Br J Surg. 2026 Jun 4;113(6):znag062. doi: 10.1093/bjs/znag062.
PubMed 42161329Jonis YMJ, Wolfs JAGN, Hummelink S, Tielemans HJP, Keuter XHA, van Kuijk S, Ulrich DJO, van der Hulst RRWJ, Qiu SS. The 6 month interim analysis of a randomized controlled trial assessing the quality of life in patients with breast cancer related lymphedema undergoing lymphaticovenous anastomosis vs. conservative therapy. Sci Rep. 2024 Jan 26;14(1):2238. doi: 10.1038/s41598-024-52489-3.
PubMed 38278856Wolfs J, Beugels J, Kimman M, Piatkowski de Grzymala AA, Heuts E, Keuter X, Tielemans H, Ulrich D, van der Hulst R, Qiu SS. Improving the quality of life of patients with breast cancer-related lymphoedema by lymphaticovenous anastomosis (LVA): study protocol of a multicentre randomised controlled trial. BMJ Open. 2020 Jan 15;10(1):e035337. doi: 10.1136/bmjopen-2019-035337.
PubMed 31948992
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving the Quality of Life of Patients With Breast Cancer-related Lymphedema by Lymphaticovenous Anastomosis (LVA): A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02790021
- Acronym / sponsor ID
- NL67059.068.18
- Conditions
- Lymphedema
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 7 Jan 2025 (actual)
- Study completion
- 7 Jan 2025 (actual)
- First posted
- 3 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Research question: Is lymphaticovenous anastomosis (LVA) for the treatment of breast cancer-related lymphedema of the arm (BCRL) more effective and cost-effective compared to standard conservative treatment? Hypothesis: LVA improves the health-related quality of life of patients who developed BCRL after breast cancer treatment and is cost-effective compared to conservative treatment. Study design: A multicenter randomised controlled trial (RCT) consisting of two treatment groups: conservative treatment (group A) and LVA (group B). The study is conducted in Maastricht University Medical Center, Radboud University Medical Center, Zuyderland Medical Center and Canisius-Wilhelmina Hospital. Study population: Women over 18 years old who underwent (axillary) treatment for breast cancer presenting with early stage lymphedema of the arm for which they received at least three months conservative treatment Intervention: LVA involves anastomosing lymphatic vessels to small veins to bypass obstructions in the lymphatic system.
Usual care: Complex decongestive therapy (CDT) which includes skin care, manual lymphatic drainage, and compression therapy. Outcome measures: The primary outcome is health-related quality of life after 12 months follow-up measured with the Lymph-ICF questionnaire. Secondary outcomes are (in)direct costs, QALYs, cost-effectiveness ratio, the discontinuation rate of conservative treatment, and excess limb volume. Sample size: A total of 120 patients will be included and randomised in two groups of 60 patients each.
Cost-effectiveness analysis: A trial-based economic evaluation is performed from the societal perspective to determine the cost-effectiveness, expressed in an incremental cost-effectiveness ratio (ICER) (i.e. cost per QALY gained), of LVA compared to CDT. Direct and indirect cost data is collected on the patient-level. The difference in QALYs is assessed with the EQ-5D-5L questionnaire. A Budget Impact Analysis (BIA) will be performed to analyse the financial consequences related to implementing LVA. Time schedule: Patient inclusion will take maximally 21 months. With a follow-up of 24 months, the total study period will be 48 months. The last three months are used for data analysis. Outcome assessment is at inclusion (before randomisation) and 3, 6, 12, 18, and 24 months later.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Complex decongestive therapy | No intervention | –Group A will continue complex decongestive therapy consisting of skin care, manual lymphatic drainage, and compression therapy using compression stockings. |
| Lymphaticovenous anastomosis (LVA) | Experimental | Procedure: Lymphaticovenous anastomosis (LVA)Group B will undergo an LVA procedure under local anesthesia in surgical daycare setting. Patients are not allowed to wear compression stockings or have decongestive therapy for four weeks after the surgery. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Women over 18 years old
- Treated for early stage breast cancer and who underwent an sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND) or axillary radiotherapy
- Early stage lymphedema of the arm (ISL classification stage I/IIa; pitting edema without fibrosis) with viable lymphatic vessels as determined by indocyanin green (ICG) lymphography
- Already received at least three months of complex decongestive therapy (CDT) prior to inclusion
- Primary breast cancer
Key exclusion criteria (8 listed)
- Male sex
- Late stage lymphedema of the arm (ISL classification IIb/III lymphedema) with evident fat deposition and/or fibrosis
- History of earlier lymph reconstruction efforts
- Recurrent breast cancer
- Distant breast cancer metastases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lymphaticovenous anastomosis (LVA)Also: LVALVA is a minimally invasive procedure that can be performed under local anesthesia. Indocyanine green (ICG) lymphography is used to visualize the (obstructed) lymphatic vessels. When using the images as a guide, the lymphatic pathways and the sites for incisions for lymphaticovenous anastomoses are marked with a pen. The patient's limb is then prepared for surgery. Under a surgical microscope the lymphatic vessels are identified and viable lymphatic vessels are anastomosed to similarly sized adjacent recipient venules in the subdermal plane. | Procedure or surgery | Lymphaticovenous anastomosis (LVA) |
Primary outcome
Health-related quality of life: Lymph-ICF questionnaire
Time frame: 12 months
To assess the efficacy of the treatment on disease-related symptoms we will use the "Lymphedema Functioning, Disability and Health" (Lymph-ICF)" questionnaire. This disease-specific questionnaire assesses the impairments in function, activity limitations, and participation restrictions of patients with arm lymphedema. This is a validated questionnaire, based on 5 domains with 29 questions. Each of the 29 questions corresponds to a score between 0-100. The total score on the Lymph-ICF is equal to the sum of the scores on the questions divided by the total number of answered questions. A higher score on the Lymph-ICF indicates more problems with functioning related to arm lymphedema.
3 secondary outcomes
Cost-effectiveness of LVA compared to complex decongestive therapy
Time frame: 24 months
Excess limb volume
Time frame: 24 months
Discontinuation rate conservative therapy
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2025.
- Derived from this study: PubMed 42161329Kleeven A, Jonis YMJ, Currie O, Wolfs J, Kimman M, Tielemans H, van der Hulst RRWJ, Hummelink S, Qiu SS. Economic evaluation of lymphaticovenous anastomosis versus conservative therapy for breast cancer-related lymphoedema: secondary outcome analysis of a randomized clinical trial. Br J Surg. 2026 Jun 4;113(6):znag062. doi: 10.1093/bjs/znag062.
- Derived from this study: PubMed 38278856Jonis YMJ, Wolfs JAGN, Hummelink S, Tielemans HJP, Keuter XHA, van Kuijk S, Ulrich DJO, van der Hulst RRWJ, Qiu SS. The 6 month interim analysis of a randomized controlled trial assessing the quality of life in patients with breast cancer related lymphedema undergoing lymphaticovenous anastomosis vs. conservative therapy. Sci Rep. 2024 Jan 26;14(1):2238. doi: 10.1038/s41598-024-52489-3.
- Derived from this study: PubMed 31948992Wolfs J, Beugels J, Kimman M, Piatkowski de Grzymala AA, Heuts E, Keuter X, Tielemans H, Ulrich D, van der Hulst R, Qiu SS. Improving the quality of life of patients with breast cancer-related lymphoedema by lymphaticovenous anastomosis (LVA): study protocol of a multicentre randomised controlled trial. BMJ Open. 2020 Jan 15;10(1):e035337. doi: 10.1136/bmjopen-2019-035337.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
René Van der Hulst, MD, PhD study director
Maastricht University Medical Center
Shan Shan Qiu Shao, MD, PhD principal investigator
Maastricht University Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lymphaticovenous anastomosis (LVA) in people with Lymphedema, run by Maastricht University Medical Center at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Health-related quality of life: Lymph-ICF questionnaire (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02790021, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2025.