Non-inferiority of Compression Bandage Alone in Lower Extremity Lymphedema Management

April 23, 2026 updated by: Elif Duygu, Abant Izzet Baysal University

MANUAL LYMPH DRAINAGE IN LOWER EXTREMITY LYMPHEDEMA MANAGEMENT: AN ESSENTIAL COMPONENT OR AN OPTIONAL EXTRA ? - A SINGLE-BLIND, RANDOMIZED NON-INFERIORITY TRIAL

Lymphedema is much more than a disease with edema. Impaired lymphatic drainage triggers adipose tissue deposition and fibrosis. Fibrosis causes lymphatic vessel dysfunction. Therefore, treatment of fibrosis is important. The gold standard of treatment for lymphedema is complex decongestive physiotherapy. In this treatment method consisting of two phases and four components in each phase, each component has its own effect. Compression is the main component of these components in terms of edema reduction. The effect of manual lymph drainage, another component, on edema and fibrosis is contradictory. Although there are studies evaluating fibrosis in lower extremity lymphedema in the literature, there is no study evaluating the effect of treatment on fibrosis and comparing two different methods evaluating fibrosis.

Research question: What is the effect of manual lymph drainage in addition to compression therapy on fibrosis, edema, skin and subcutaneous tissue thickness, and quality of life.

The primary aim of this study was to evaluate the effect of manual lymph drainage applied as an adjunct to compression therapy on fibrosis in individuals with lower extremity lymphedema. The secondary aim of the study was to evaluate the effect of manual lymph drainage in addition to compression therapy on skin and subcutaneous tissue thickness, edema and quality of life.

Patients with lower extremity lymphedema will be randomly allocated to the compression group and manual lymph drainage + compression group. Fibrosis in the tissues of the individuals will be evaluated by ultrasound and SkinFibrometer device, skin and subcutaneous tissue thickness will be evaluated by ultrasound, edema perimeter measurement will be converted to volume, and quality of life will be evaluated by Lymphedema Quality of Life Questionnaire-Lower Extremity before and after treatment. Individuals will be randomized to either 20 sessions of compression bandage or 20 sessions of compression bandage with manual lymph drainage. Both groups will include skin care and exercise components of complex decongestive physiotherapy.

This study will provide important data on whether manual lymph drainage is clinically necessary in the treatment of lower limb lymphedema.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Lower extremity lymphedema (LE) is a chronic disease characterized by the accumulation of protein-rich fluid in the interstitial space and inflammation. It is classified as primary and secondary lymphedema. Primary LE is caused by developmental defects of the lymphatic system, whereas secondary LE is caused by subsequent damage to the lymphatic system. The biggest cause of secondary LE in western countries is cancer surgery.

Lower extremity LE is not a disease characterized only by edema. As the disease progresses, adipose tissue increases and fibrosis is observed. Fibrosis is defined as excessive accumulation of extracellular matrix products. Fibrosis is a well-known cause of organ dysfunction in many systems, including the liver, kidney, heart, and skin. This condition also occurs in limb LL and is a characteristic pathological change seen in LL. The increase in adipose tissue and fibrosis triggered by the presence of lymph fluid leads to increased skin and subcutaneous tissue thickness. These changes increase as the duration and stage of the disease progress.

Inflammation due to impaired lymph drainage triggers the fibrosis process. Histological and immunohistochemical specimens from clinical and experimental skin tissues of patients with LE reveal an increase in collagen fibers in edematous skin due to fibrosis. Fibrosis in LE is not limited to the skin but has also been detected in subcutaneous tissue, including adipose tissue. It has been reported that adipocytes in adipose tissue with LE have hypertrophic changes and larger adipose tissue lobules, and these lobules are surrounded by thick collagen fibers and interstitial lymphatic fluid. It has been reported that collagen accumulation in subcutaneous fat was observed in mouse models of LE. This leads to hardening of the tissue , resulting in non-depressed edema. Fibrosis in the tissue causes lymphatic vessel dysfunction and reduces lymphatic capacity, leading to worsening of LE. It has been reported that fibrotic changes in lymphedema can be partially reversed with complex decongestive physiotherapy (CDF). CDF is a conservative treatment method accepted as the gold standard in the treatment of LE. It consists of two phases: discharge and protection. While the unloading phase aims to reduce limb volume, the preservation phase aims to maintain the reduced volume. The unloading phase consists of 4 main components: manual lymph drainage (MLD), skin care, compression, and exercise. In the protection phase, compression bandages are replaced by compression garments, and manual lymph drainage is replaced by self/simple lymph drainage. The drainage phase lasts at least 2-4 weeks, and the protection phase lasts for life Each treatment component has a unique mechanism of action in the treatment of lymphedema. MLD is a gentle massage technique that aims to move the skin and connective tissue, thus stretching the anchor filaments connected to the lymphatic capillaries and opening the lymphatic capillaries without causing hyperemia. There are different holding techniques. MLD is thought to increase the transport rate of lymphatic fluid, develop new pathways for lymphatic drainage from edematous areas to adjacent non-edematous areas, remove protein deposits from the tissue, and break down fibrotic tissue. Compression is to create more tissue pressure during contractions by resisting muscle activity. This is the strongest stimulation for lymph drainage. Compression also prevents fluid accumulation in the tissue by reducing capillary filtration. It allows resorption of fluid in the interstitial space. It displaces fluid to non-compressed areas where drainage is normal. Compression is also thought to be effective in the destruction of fibrosclerotic tissue.

In the literature, the effect of MLD and compression applications on edema has been frequently evaluated, and the effectiveness of compression bandaging has been shown, although the effect of MLD on edema reduction is contradictory. Nevertheless, it has been suggested that MLD may also be effective in fibrotic tissue. However, although there are evaluation studies showing fibrosis in tissue with LE, there are no randomized controlled trials showing the effect of MLD and compression on fibrotic tissue in lower extremity LE. Similarly, there are no studies comparing the effect of lymphedema treatments on fibrosis using two different assessment methods. The primary aim of this study was to evaluate the effect of MLD applied as an adjunct to compression therapy on fibrosis in individuals with lower extremity LE. The secondary aim of the study was to evaluate the effect of MLD applied in addition to compression bandage on skin and subcutaneous tissue thickness, edema, and quality of life.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey (Türkiye)
    • Merkez
      • Bolu, Merkez, Turkey (Türkiye), 14030
        • Bolu abant Izzet Baysal University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • According to the criteria of the International Society of Lymphology Stage 2 and 3 lower extremity LE to volunteer to participate in the study
  • To be between the ages of 18-80
  • LE involving the entire lower extremity

Exclusion Criteria:

  • Acute deep vein thrombosis
  • Acute infection
  • Peripheral arterial disease in the lower extremity
  • To have systemic diseases that may cause edema other than LE (renal failure, liver failure, heart failure, etc.)
  • Chronic venous insufficiency
  • Allergy to materials used in treatment
  • Mental/cognitive problems that will affect cooperation
  • Loss of sensation
  • Presence of scleroderma in the treatment area
  • Active cancer
  • Radiogenic fibrosis in the treatment area

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Compression Group
In compression therapy, multicomponent inelastic compression bandages bandages will be applied (Misra et al., 2023). The individual will be fitted with a stockinet beforehand. Fingers will be bandaged. Then, the extremity will be cylindricalized with a cotton roller or sponge. Subsequently, the foot and ankle will be bandaged using a 6 cm short-stretch bandage. An 8 cm short-stretch bandage will be applied starting from the foot and progressing upward above the ankle. A 10 cm short-stretch bandage will then be applied, beginning at the ankle and wrapping upward. The next bandages will be wrapped upwards starting from the places where the pressure is low. The compression bandage will remain on the patient's leg for approximately 23 hours. When the individual arrives the next day, the bandage will be removed and reapplied. The application time of the inelastic bandage is approximately 20-30 minutes. Compression therapy will be applied 5 days a week for 4 weeks (20 sessions)
Other: Manual lymphatic drainage added to compression
Manual lymphatic drainage will be added to multicomponent inelastik compression bandage, skin care and simple exercises
Experimental: Compression+MLD Group

Participants in the group receiving MLD in addition to compression therapy will undergo a 30-40-minute MLD session to facilitate the entry of interstitial fluid into lymphatic capillaries and enhance lymph propulsion (Misra et al., 2023). The MLD will be performed with gentle pressure of approximately 30-40 mmHg, ensuring the skin and connective tissue move together without sliding on the skin.

After the MLD session, a multilayer bandaging will be applied to the extremity, which the patient will wear for approximately 23 hours. The bandage will be removed and reapplied during the patient's visit the following day.

The combined therapy of compression and MLD will be administered five days a week for four weeks (20 sessions in total). Each session will last approximately 50-70 minutes.
Other: Compression bandage
A multicomponent inelastic compression bandage will be applied to the patient. Skin care and simple exercises will be added to intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Edema Assessment
Time Frame: Baseline, four week later

Edema will be assessed by circumference measurements with the patient in a supine position. Measurements will start 10 cm from the heel. Along the lateral aspect of the leg, marks will be made at 8 cm intervals, and circumference measurements will be taken at these points along the extremity.

Using a non-elastic tape measure 1 cm in width, measurements will be conducted without compressing the tissue and ensuring the ends of the tape do not overlap. Measurements will be recorded in centimeters. This process will be performed bilaterally.

The recorded circumferences will then be converted into volume using the truncated cone formula, as extremities are considered geometrically as truncated cones for this calculation.
Baseline, four week later

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of Skin and Subcutaneous Tissue Thickness
Time Frame: Baseline and four week later
The evaluation of skin and subcutaneous tissue thickness will be performed by a specialized radiologist using a LOGIQ ultrasound system (GE Healthcare, USA) equipped with a 6-15 MHz linear probe. Measurements will be conducted with the individual in a supine position. To optimize the passage of ultrasound waves, ultrasound gel will be applied between the probe and the skin. The ultrasound probe will be positioned perpendicularly to the skin, and brightness mode (B-mode) images will be obtained without applying additional compression to the skin. For skin thickness, the measurement will include the distance between two fine echogenic lines encompassing the hypoechoic dermis, as described comprehensively in previous studies, and will be recorded in millimeters. The subcutaneous distance will be measured as the distance in millimeters between the posterior echogenic line of the dermis and the anterior echogenic line of the muscular fascia
Baseline and four week later
Assessment of Fibrosis Using the SkinFibroMeter
Time Frame: Baseline and four week later

The patient will lie in a supine position on a treatment bed with the lower extremities relaxed. The SkinFibroMeter probe will be briefly (0.5 seconds) pressed perpendicularly against the skin. Each stiffness value will be calculated as the average of five consecutive successful measurements at the same site. If the applied force or measurement duration is incorrect, a 'USER ERROR' message will be displayed, and the measurements will be repeated.

Fibrosis will be measured at 17 points on each lower extremity. Specific landmarks will be identified, including 5 cm above the joint of the second toe, 5 cm above the lateral malleolus, 10 cm below the inferior border of the patella, and 10 cm and 20 cm above the superior border of the patella. On the thigh and calf, medial, lateral, posterior, and anterior midline points corresponding to the same circumferential level as these landmarks will also be marked
Baseline and four week later

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abant Izzet Baysal University

Collaborators

The Scientific and Technological Research Council of Turkey

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2024

Primary Completion (Actual)

March 1, 2026

Study Completion (Actual)

April 1, 2026

Study Registration Dates

First Submitted

December 20, 2024

First Submitted That Met QC Criteria

December 20, 2024

First Posted (Actual)

December 27, 2024

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BAIBU-FTR-ED-004

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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