Lymphovenous Bypass Manage Venous Leg Ulcers

Lymphovenous Bypass (LVB) Promotes Healing Process of Venous Leg Ulcers

Leg ulcers are areas of epidermal discontinuity in lower limbs with causes of venous, arterial, diabetic, pressure, traumatic, allergic, or inflammation. Chronic venous leg ulcers (VLUs) are defined as leg ulcers persisting for 4 weeks or more, a.k.a C6 in CEAP classification of chronic venous insufficiency (CVI) and account for up to 70% of all chronic leg ulcers exhibiting overall prevalence of up to 2% in the general population of western countries with significant morbidity and a negative socioeconomic impact. Wound care, debridement, bed rest with leg elevation, and compression are basic approaches for chronic VLUs. Meanwhile, numerous medical and surgical interventions were developed to promote wound healing and to prevent recurrence by focusing on pathophysiology of chronic VLUs. However, many strategies just have adjuvant effects or exert debatable benefits.

The lymphatic system been considered important for removal of excessive fluid from the interstitial space, absorption of fat from the intestine and the immune system, actively involved in regulation of immune cell trafficking and inflammation. Emerging lymphovenous bypass (LVB), a supermicrosurgical technique diverting lymphatic drainage into venous system in dealing with lymphedema, not only restores TH1 and TH2 imbalance, but decreases oxidative stress and increases antioxidant capacity in the serum of lymphedema patients. Clinically, LVB could be an alternative treatment option for patients with lymphorrhea.

Based on these facts, the investigators hypothesis that lymphatic hypertension and lymph impregnation contributes chronic venous leg ulcer formation and propose a novel strategy, using LVB to treat patients with refractory/recurrent chronic VLUs. The preliminary results revealed promising results and the investigators would go on clinical trials.

Study Overview

• Status: Completed
• Conditions: Venous Leg Ulcer; Lymphovenous Edema
• Intervention / Treatment: Procedure: Lymphovenous bypass, including lymphaticovenular anastomosis/implantation

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Sung-Chuan Chao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: 20~80 years
• Gender: All
• Poor wound healing after standard wound management for 4 weeks
• Deep vein thrombosis (DVT) has been ruled out by Duplex and Computer tomography or DVT has been treated
• Wound care with nursing specialty
• Recognize and agree to join this trial

Exclusion Criteria:

• Autoimmune status, such as systemic lupus erythematosus
• Heart, lung, kidney or liver failure patients
• Radiation related wound or cancer wound
• Those who cannot understand the trial
• Age less than 20 years or elder than 80 years
• Pregnancy
• Those who was Risky to receive general anesthesia or surgery
• Allergy to Patent Blue V or Gentian Violet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venous leg ulcers patients undergoing lymphovenous bypass	Procedure: Lymphovenous bypass, including lymphaticovenular anastomosis/implantation; Lymphovenous bypass (LVB) is a supermicrosurgical technique by diverting lymphatic drainage into venous system. Simultaneously, we performed LVB at ipsilateral foot dorsum and debride the VLUs and resurface the wound primarily or by skin graft depending on defect size.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healing process of venous leg ulcers	Clinical assessment of wound healing in surface area (centimeter square)	Postoperative 24 weeks
Healing process of venous leg ulcers	Clinical assessment of wound healing in surface area (centimeter square)	Postoperative 4~8 weeks
Healing process of venous leg ulcers	Clinical assessment of wound healing in surface area (centimeter square)	Postoperative 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Venous Clinical Severity Score (VCSS), 0 (minimum) ~ 30 (maximum), higher scores mean a worse outcome	Scoring system of chronic venous insufficiency	Postoperative 12 weeks
The venous leg ulcer quality of life (VLU-QoL) questionnaire (Chinese version verified), 0 (minimum) ~ 100 (maximum), higher scores mean a worse outcome	The questionnaire evaluates 3 dimesions including activities, psychological and symptom distress aspect of patient having venous leg ulcers.	Preoperative
The venous leg ulcer quality of life (VLU-QoL) questionnaire (Chinese version verified), 0 (minimum) ~ 100 (maximum), higher scores mean a worse outcome	The questionnaire evaluates 3 dimesions including activities, psychological and symptom distress aspect of patient having venous leg ulcers.	Postoperative 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin biopsy for hematoxylin and eosin stain	collagen degradation and immunocytes infiltration	Intraoperative
Skin biopsy for hematoxylin and eosin stain	collagen degradation and immunocytes infiltration	Postoperative 3 months
Skin biopsy for immunohistochemistry stain	chemokines (Interleukin-1, Interleukin-8, Tumor Necrosis Factor-alpha), Matrix Metalloproteinases stain	Intraoperative
Skin biopsy for immunohistochemistry stain	chemokines (Interleukin-1, Interleukin-8, Tumor Necrosis Factor-alpha), Matrix Metalloproteinases stain	Postoperative 3 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Study Director: Sung-Chuan Chao, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Actual): March 1, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: September 6, 2021
• First Submitted That Met QC Criteria: September 26, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): July 17, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Chronic Venous Insufficiency; Lymphovenous Bypass
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Skin Ulcer; Varicose Veins; Ulcer; Leg Ulcer; Varicose Ulcer
• Other Study ID Numbers: 202105094RIND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No