Protocol: Effect of Lymphovenous Anastomosis in the Treatment of Lower Limb Lymphedema - Pragmatic Assessor-Blinded Open-Label Randomized Controlled Trial (PrCT)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 4
- 主要终点
- Change in L-Dex ratio (bioimpedance spectroscopy) at 12 months.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Outcome assessors remain unaware of group allocation; participants wear adhesive bandage over potential incision sites at follow-up visits.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
结局指标
主要结局
Change in L-Dex ratio (bioimpedance spectroscopy) at 12 months.
时间窗: 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.
次要结局
- Change in Limb Volume by Tape Measurement(Baseline, 6 months, 12 months, 24 months)
- Change in Limb Volume by Perometry(Baseline, 6 months, 12 months, 24 months)
- Change in Lymphoedema Quality of Life Questionnaire (LYMQOL)(Baseline, 6 months, 12 months, 24 months)
- Change in Limb Mass by DXA(Baseline, 6 months, 12 months, 24 months)
- Change in Compression Garment Use(Baseline to 24 months)
- Incidence of Erysipelas Infections(Baseline, 6 months, 12 months, 24 months)
- Change in EuroQol Five Dimension Five Level (EQ-5D-5L) utility index(Baseline, 6 months, 12 months, 24 months)
- Change in Lymphoscintigraphy(Baseline, 6 mo, 12 mo, 24 mo)
- Change in Limb Volume by Tape Measurement(Baseline, 6 months, 12 months, 24 months)
- Change in Limb Volume by Perometry(Baseline, 6 months, 12 months, 24 months)
- Change in Limb Mass by DXA(Baseline, 6 months, 12 months, 24 months)
- Change in Compression Garment Use(Baseline to 24 months)
- Incidence of Erysipelas Infections(Baseline, 6 months, 12 months, 24 months)
- Change in Lymphoscintigraphy(Baseline, 6 mo, 12 mo, 24 mo)
研究者
Amar Bucan
Medical doctor
Herlev and Gentofte Hospital