LymphedemaNCT07073586
Effect of Lymphovenous Anastomosis on Lower Limb Lymphedema: Pragmatic Randomized Controlled Trial
A study testing Lymphovenous Anastomosis and Complete Decongestive Therapy in people with Lymphedema and Lymphoedema, run by Herlev and Gentofte Hospital at 2 sites in Denmark.
Trial summary
This multicentre pragmatic randomised controlled trial evaluates lymphovenous anastomosis (LVA) for lower-limb lymphedema (LLL) in Denmark. Adults with unilateral or bilateral International Society of Lymphology (ISL) stage 1-2a LLL who have completed protocol-defined Complete Decongestive Therapy (CDT) are randomised… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphedema, Lymphoedema, Lymphoedema of Leg
- What is being tested?
- Lymphovenous Anastomosis and Complete Decongestive Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 2 sitesDenmark
- Study dates
- 9 May 2025to Aug 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- LLL International Society of Lymphology (ISL) stage 1-2a (both primary and secondary lymphedema and both unilateral and bilateral)
- Cancer-free with no recurrence for at least one year
- Age 18 or above
- Circumference of the affected leg is at least 1 cm larger than the non-lymphedema leg at the most affected site of lymphedema.
- Proficiency in Danish language, and ability to provide informed consent.
- Dermal Backflow Stage 0-4
Who cannot join
- LLL International Society of Lymphology (ISL) stage 2b-3
- Medical conditions contraindicating surgical intervention or anesthesia, such as severe heart or lung disease
- Allergy to ICG
- Ongoing infections or skin diseases in the affected limb
- Previous surgery or other treatment modalities that could interfere with the study results (previous LVA, liposuction or similar).
- Dermal Backflow Stage 5
Show all 14Show fewer
- Active cancer
- Heart or kidney conditions that can cause leg swelling
- A BMI above 28 kg/m²
- Current smoker
- Any foreign objects in the lower extremities (e.g., metal implants, prostheses)
- Venous insufficiency Unilateral weakness in the lower extremity (e.g., after a stroke)
- Known iodine allergy (contraindication for ICG injection)
- Leg length discrepancy (anisomelia) > 1.5 cm
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark2 sites, 2 recruiting
- Recruiting
Department of Plastic Surgery, Herlev and Gentofte Hospital
Herlev, Region Sjælland, 2730
Amar Bucan, Medical doctor, +4538689045, amar.bucan.02@regionh.dk
Lisbet Rosenkrantz Hölmich, MD, Professor, DMSc, +4538689045, lisbet.rosenkrantz.hoelmich@regionh.dk
- Not yet recruiting
Department of Plastic Surgery, Odense University Hospital
Odense, Fyn, 5
Jørn Bo Thomsen, MD, PhD, +45 65 41 24 45, joern.bo.thomsen@rsyd.dk
About this study
Official title: Protocol: Effect of Lymphovenous Anastomosis in the Treatment of Lower Limb Lymphedema - Pragmatic Assessor-Blinded Open-Label Randomized Controlled Trial (PrCT)
This multicentre pragmatic randomised controlled trial evaluates lymphovenous anastomosis (LVA) for lower-limb lymphedema (LLL) in Denmark. Adults with unilateral or bilateral International Society of Lymphology (ISL) stage 1-2a LLL who have completed protocol-defined Complete Decongestive Therapy (CDT) are randomised 1:1 to
Intervention arm - LVA surgery plus ongoing compression care
Read more
Control arm - Compression care only
Recruitment takes place at the Departments of Plastic Surgery, Herlev-Gentofte Hospital and Odense University Hospital. Outcomes are assessed by independent blinded staff at baseline, 6, 12 and 24 months. A biopsy substudy in ten LVA patients explores inflammatory and fibrotic changes. Primary endpoint is change in L-Dex ratio at 12 months. Secondary endpoints include limb volume, infection rate, lymphoscintigraphy findings, patient-reported outcomes, compression-garment use and anastomosis patency.
The trial follows Good Clinical Practice and General Data Protection Regulation (GDPR). Patients are covered by the Danish public patient-compensation scheme. Results will be published regardless of outcome, and control participants may opt for LVA after the 12-month visit.
Read the detailed description
Lower-limb lymphedema (LLL) causes chronic swelling, pain, recurrent infections and impaired quality of life. Complete Decongestive Therapy (CDT) is standard care, yet many patients have persistent disease. Lymphovenous anastomosis (LVA) is a super-microsurgical procedure that diverts lymph into the venous system, but robust randomised evidence in LLL is lacking
This multicentre pragmatic randomised trial will test whether lymphovenous anastomosis (LVA) can reduce lower-limb lymphedema and improve life quality in adults who have completed Complete Decongestive Therapy (CDT). The study is carried out at two Danish university hospitals that routinely manage complex lymphedema. A computer system assigns participants in a 1:1 ratio to either LVA plus compression care or compression care alone. Surgeons create as many anastomoses as possible under general anaesthesia, using indocyanine green mapping to find suitable lymphatic vessels.
Adults aged 18 years or older with International Society of Lymphology stage (ISL) 1 or 2a lymphedema of one or both legs can join if they have finished CDT. Key exclusions are stage 2b or 3 disease, body-mass index (BMI) above 28, active cancer, severe medical illness, or prior lymphedema surgery.
The primary outcome is the change in L-Dex ratio, from baseline to 12 months. Secondary outcomes measured at baseline, 6, 12 and 24 months include limb volume by tape, perometry and dual-energy X-ray absorptiometry, infection frequency, lymphoscintigraphy findings, quality-of-life scores (Lymphedema Quality of Life Questionnaire (LYMQOL) and EuroQol Five Dimension Five Level (EQ-5D-5L)) and use of compression garments. At 12 months the patency of the anastomoses is checked with indocyanine green lymphography in the surgical arm. A small substudy in ten surgical participants will compare inflammatory markers and tissue structure in paired skin biopsies collected during surgery and again 6 months later.
Participants attend the clinic for baseline, 6-month and 12-month visits and return at 24 months for long-term follow-up. Conservative measures such as compression garments may continue (but not reduced in 12 months for LVA-group), but no other surgical or medical lymphedema procedures are allowed during the study period.
All data are entered into a secure electronic database and analysed according to Good Clinical Practice, the Danish Code of Conduct for Research Integrity and General Data Protection Regulation (GDPR). The regional research ethics committee has approved the protocol, and participants are covered by the Danish public patient-compensation scheme. Results will be published in peer reviewed journals no matter whether LVA shows benefit, harm or no difference.
- Conditions
- Lymphedema, Lymphoedema, Lymphoedema of Leg, Lymphedema of Leg
- Being tested
- Lymphovenous Anastomosis, Complete Decongestive Therapy
- Keywords
- Lymphovenous Anastomosis, LVA, Lower Limb Lymphedema, Leg Lymphedema, Randomized Controlled Trial, CDT, Compression Therapy
- Medical subject headings
- Lymphedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lymphovenous AnastomosisProcedure or surgery
Microsurgical creation of multiple lymphatic-venous connections in the most affected limb under general anaesthesia.
Complete Decongestive TherapyOther
Also called CDT
Complete Decongestive Therapy, comprising bandaging, skin care and exercise, followed by compression garments.
| Study group | Role | What they receive |
|---|---|---|
| Lymphovenous anastomosis (LVA) + Compression Therapy | Experimental | LVA + conservative care. Patient must have undergone Complete Decongestive Therapy (CDT) and comply with the compression treatment. Follow-up at 6, 12 and 24 months includes blinded assessment of L-Dex, tape and perometry volumes, DXA, lymphoscintigraphy, erysipelas incidence and LYMQOL/EQ-5D-5L scores; patency is checked by ICG-lymphography at 12 months. A subset of 10 patients with unilateral lymphedema also provides paired skin biopsies (both legs) at surgery and again 6 months postoperatively for biomarker and histological analysis. Receives: Procedure: Lymphovenous Anastomosis; Other: Complete Decongestive Therapy |
| Compression Therapy Alone | Active comparator | Conservative care alone. Participants complete standard Complete Decongestive Therapy, comprising bandaging, skin care and exercise, followed by compression garments. Outcomes are assessed by the same blinded schedule as the LVA arm at baseline, 6, 12 and 24 months. Participants may elect LVA crossover after the 12-month evaluation if desired. Receives: Other: Complete Decongestive Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in L-Dex ratio (bioimpedance spectroscopy) at 12 months.
Difference in L-Dex ratio of the most affected leg, measured with the SOZO bioimpedance device (ImpediMed). Measurements are performed by blinded assessors after 48 h without compression garments.
Measured: Baseline to 12 months
Secondary outcomes (8)
Change in Limb Volume by Tape Measurement
Difference in limb volume using tape measurements and calculating using formulas.
Measured: Baseline, 6 months, 12 months, 24 months
Change in Limb Volume by Perometry
Difference in limb volume obtained with optoelectronic perometry (automatic three-dimensional scan of the leg).
Measured: Baseline, 6 months, 12 months, 24 months
Change in Limb Mass by DXA
Difference in limb mass of the affected leg measured with dual-energy X-ray absorptiometry.
Measured: Baseline, 6 months, 12 months, 24 months
Change in Compression Garment Use
Change of compression class, change in daily use, or continue/discontinue compression garments. Data collected by questionnaire.
Measured: Baseline to 24 months
Incidence of Erysipelas Infections
Number of erysipelas episodes in the affected limb
Measured: Baseline, 6 months, 12 months, 24 months
Change in Lymphoedema Quality of Life Questionnaire (LYMQOL)
Difference in total score of the Lymphoedema Quality of Life Questionnaire for lower limb lymphedema.
Item and domain scores run from 1 to 4. Higher scores mean a worse quality of life.
The separate "overall quality of life" item uses a 0 to 10 scale. Higher scores mean a better quality of life.
Measured: Baseline, 6 months, 12 months, 24 months
Change in EuroQol Five Dimension Five Level (EQ-5D-5L) utility index
Using the Danish value set, scores range from -0.757 (worst imaginable health) to 1.000 (full health). Higher scores mean a better health-related quality of life
Measured: Baseline, 6 months, 12 months, 24 months
Change in Lymphoscintigraphy
Change in lymphoscintigraphy transport. Scans read by blinded nuclear-medicine specialists.
Measured: Baseline, 6 mo, 12 mo, 24 mo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2025
- Study start9 May 2025
- Primary completionAug 2027 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphedemaStudies 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
- Two-arm, assessor-blinded, open-label, pragmatic randomized controlled trial comparing LVA plus conservative therapy with conservative therapy alone.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Herlev and Gentofte Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amar Bucan, Herlev and Gentofte Hospital
- Investigators
- Lisbet Rosenkrantz Hölmich, MD, Professor, DMSc, Study chair, Department of Plastic Surgery, Herlev and Gentofte Hospital, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07073586
- Sponsor's protocol ID
- H-25012096
- Status last verified
- Jul 2025
- First submitted
- 9 Jul 2025
- Last updated
- 31 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol: Effect of Lymphovenous Anastomosis in the Treatment of Lower Limb Lymphedema - Pragmatic Assessor-Blinded Open-Label Randomized Controlled Trial (PrCT)
- ClinicalTrials.gov ID
- NCT07073586
- Acronym / sponsor ID
- H-25012096
- Conditions
- Lymphedema, Lymphoedema, Lymphoedema of Leg, Lymphedema of Leg
- Keywords
- Lymphovenous Anastomosis, LVA, Lower Limb Lymphedema, Leg Lymphedema, Randomized Controlled Trial, CDT, Compression Therapy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Herlev and Gentofte HospitalUniversity, hospital or other
- Study start
- 9 May 2025 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 18 Jul 2025 (actual)
- 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.
This multicentre pragmatic randomised controlled trial evaluates lymphovenous anastomosis (LVA) for lower-limb lymphedema (LLL) in Denmark. Adults with unilateral or bilateral International Society of Lymphology (ISL) stage 1-2a LLL who have completed protocol-defined Complete Decongestive Therapy (CDT) are randomised 1:1 to
Intervention arm - LVA surgery plus ongoing compression care
Control arm - Compression care only
Recruitment takes place at the Departments of Plastic Surgery, Herlev-Gentofte Hospital and Odense University Hospital. Outcomes are assessed by independent blinded staff at baseline, 6, 12 and 24 months. A biopsy substudy in ten LVA patients explores inflammatory and fibrotic changes. Primary endpoint is change in L-Dex ratio at 12 months. Secondary endpoints include limb volume, infection rate, lymphoscintigraphy findings, patient-reported outcomes, compression-garment use and anastomosis patency.
The trial follows Good Clinical Practice and General Data Protection Regulation (GDPR). Patients are covered by the Danish public patient-compensation scheme. Results will be published regardless of outcome, and control participants may opt for LVA after the 12-month visit.
Detailed description
Lower-limb lymphedema (LLL) causes chronic swelling, pain, recurrent infections and impaired quality of life. Complete Decongestive Therapy (CDT) is standard care, yet many patients have persistent disease. Lymphovenous anastomosis (LVA) is a super-microsurgical procedure that diverts lymph into the venous system, but robust randomised evidence in LLL is lacking
This multicentre pragmatic randomised trial will test whether lymphovenous anastomosis (LVA) can reduce lower-limb lymphedema and improve life quality in adults who have completed Complete Decongestive Therapy (CDT). The study is carried out at two Danish university hospitals that routinely manage complex lymphedema. A computer system assigns participants in a 1:1 ratio to either LVA plus compression care or compression care alone. Surgeons create as many anastomoses as possible under general anaesthesia, using indocyanine green mapping to find suitable lymphatic vessels.
Adults aged 18 years or older with International Society of Lymphology stage (ISL) 1 or 2a lymphedema of one or both legs can join if they have finished CDT. Key exclusions are stage 2b or 3 disease, body-mass index (BMI) above 28, active cancer, severe medical illness, or prior lymphedema surgery.
The primary outcome is the change in L-Dex ratio, from baseline to 12 months. Secondary outcomes measured at baseline, 6, 12 and 24 months include limb volume by tape, perometry and dual-energy X-ray absorptiometry, infection frequency, lymphoscintigraphy findings, quality-of-life scores (Lymphedema Quality of Life Questionnaire (LYMQOL) and EuroQol Five Dimension Five Level (EQ-5D-5L)) and use of compression garments. At 12 months the patency of the anastomoses is checked with indocyanine green lymphography in the surgical arm. A small substudy in ten surgical participants will compare inflammatory markers and tissue structure in paired skin biopsies collected during surgery and again 6 months later.
Participants attend the clinic for baseline, 6-month and 12-month visits and return at 24 months for long-term follow-up. Conservative measures such as compression garments may continue (but not reduced in 12 months for LVA-group), but no other surgical or medical lymphedema procedures are allowed during the study period.
All data are entered into a secure electronic database and analysed according to Good Clinical Practice, the Danish Code of Conduct for Research Integrity and General Data Protection Regulation (GDPR). The regional research ethics committee has approved the protocol, and participants are covered by the Danish public patient-compensation scheme. Results will be published in peer reviewed journals no matter whether LVA shows benefit, harm or no difference.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Two-arm, assessor-blinded, open-label, pragmatic randomized controlled trial comparing LVA plus conservative therapy with conservative therapy alone.
| Arm | Type | Receives |
|---|---|---|
| Lymphovenous anastomosis (LVA) + Compression Therapy | Experimental | Procedure: Lymphovenous Anastomosis, Other: Complete Decongestive TherapyLVA + conservative care. Patient must have undergone Complete Decongestive Therapy (CDT) and comply with the compression treatment. Follow-up at 6, 12 and 24 months includes blinded assessment of L-Dex, tape and perometry volumes, DXA, lymphoscintigraphy, erysipelas incidence and LYMQOL/EQ-5D-5L scores; patency is checked by ICG-lymphography at 12 months. A subset of 10 patients with unilateral lymphedema also provides paired skin biopsies (both legs) at surgery and again 6 months postoperatively for biomarker and histological analysis. |
| Compression Therapy Alone | Active comparator | Other: Complete Decongestive TherapyConservative care alone. Participants complete standard Complete Decongestive Therapy, comprising bandaging, skin care and exercise, followed by compression garments. Outcomes are assessed by the same blinded schedule as the LVA arm at baseline, 6, 12 and 24 months. Participants may elect LVA crossover after the 12-month evaluation if desired. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- LLL International Society of Lymphology (ISL) stage 1-2a (both primary and secondary lymphedema and both unilateral and bilateral)
- Cancer-free with no recurrence for at least one year
- Age 18 or above
- Circumference of the affected leg is at least 1 cm larger than the non-lymphedema leg at the most affected site of lymphedema.
- Proficiency in Danish language, and ability to provide informed consent.
Key exclusion criteria (14 listed)
- LLL International Society of Lymphology (ISL) stage 2b-3
- Medical conditions contraindicating surgical intervention or anesthesia, such as severe heart or lung disease
- Allergy to ICG
- Ongoing infections or skin diseases in the affected limb
- Previous surgery or other treatment modalities that could interfere with the study results (previous LVA, liposuction or similar).
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 |
|---|---|---|
| Lymphovenous AnastomosisMicrosurgical creation of multiple lymphatic-venous connections in the most affected limb under general anaesthesia. | Procedure or surgery | Lymphovenous anastomosis (LVA) + Compression Therapy |
| Complete Decongestive TherapyAlso: CDTComplete Decongestive Therapy, comprising bandaging, skin care and exercise, followed by compression garments. | Other | Compression Therapy Alone, Lymphovenous anastomosis (LVA) + Compression Therapy |
Primary outcome
Change in L-Dex ratio (bioimpedance spectroscopy) at 12 months.
Time frame: Baseline to 12 months
Difference in L-Dex ratio of the most affected leg, measured with the SOZO bioimpedance device (ImpediMed). Measurements are performed by blinded assessors after 48 h without compression garments.
8 secondary outcomes
Change in Limb Volume by Tape Measurement
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Limb Volume by Perometry
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Limb Mass by DXA
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Compression Garment Use
Time frame: Baseline to 24 months
Incidence of Erysipelas Infections
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Lymphoedema Quality of Life Questionnaire (LYMQOL)
Time frame: Baseline, 6 months, 12 months, 24 months
Change in EuroQol Five Dimension Five Level (EQ-5D-5L) utility index
Time frame: Baseline, 6 months, 12 months, 24 months
Change in Lymphoscintigraphy
Time frame: Baseline, 6 mo, 12 mo, 24 mo
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
- Individual participant dataSharing planned: No
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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.
Lisbet Rosenkrantz Hölmich, MD, Professor, DMSc study chair
Department of Plastic Surgery, Herlev and Gentofte Hospital, Denmark
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lymphovenous Anastomosis and Complete Decongestive Therapy in people with Lymphedema and Lymphoedema, run by Herlev and Gentofte Hospital at 2 sites in Denmark.
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 6 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 31 Jul 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 Denmark. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amar Bucan, Medical doctor (+4538685444, amar.bucan.02@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in L-Dex ratio (bioimpedance spectroscopy) at 12 months. (time frame: Baseline to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jul 2025.