PRELUDE Study of Lymphatic Surgery to Treat Breast Cancer Related Lymphoedema

Breast Cancer Clinical Trial

— PRELUDE  

Official title:

Prospective Randomized Evaluation of Lymphaticovenous Anastomosis Using Dynamic Imaging in Breast Cancer-related Lymphoedema

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04579029
• Other study ID #: CCR4772
• Status: Recruiting
• Phase: N/A
• Start date: October 13, 2021
• Est. completion date: April 2024

Study information

• Verified date: January 2023
• Source: Royal Marsden NHS Foundation Trust
• Contact: Kelvin WD Ramsey, FRCS(Plast)
• Phone: 02078082208
• Email: Kelvin.Ramsey[@]rmh.nhs.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lymphoedema is a chronic debilitating disease that can have severe adverse effects on day-to-day life causing great physical and visual discomfort. The clinical presentation is characterised by chronic swelling of limbs, accompanied by localised pain, skin changes and recurrent infections. It is caused by a disruption in lymphatic flow which prevents the normal circulation of interstitial fluid (situated in the spaces between the cells of the body), resulting in swelling of the affected limb. It can be primary (cause unknown) or secondary to a number of causes such as malignancy, trauma, surgery, radiotherapy, infection, or venous disease.

In breast cancer treatment, axillary surgery and radiotherapy significantly damage normal lymphatic drainage of the upper limb, causing lymphoedema in 1-in-5 patients.

There is a growing body of evidence that this chronic and debilitating condition can be better managed through early surgical intervention rather than the current conservative management, which rely on pressure garments and massage. This surgical intervention, lymphaticovenous anastomosis (LVA), joins up a number of the draining lymphatic vessels to correspondingly sized veins on the affected limb using microsurgical techniques. A special dye and camera system is used to facilitate identifying lymph vessels. This creates a new drainage pathway for the lymph fluid around the area of disruption, improving lymphatic flow. Volume reduction is expected and this would be expected to provide quality of life benefits for the patients.

This study seeks to compare the outcomes from both therapies and determine whether LVA surgery can help to improve the physical burden and quality of life for patients affected by lymphoedema. Furthermore, lymphoedema places a substantial burden on NHS services. If this trial is successful, LVA surgery could improve patient outcomes and reduce the overall cost of treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Breast cancer patients treated with axillary surgery who have developed post-surgical lymphoedema (increase in limb volume by >10% for 1 month or longer)

• Patients must have completed their adjuvant therapy (excluding hormonal/long term Rx)

• Patients must be within 6 months of having developed documented lymphoedema

Exclusion Criteria:

• • Contraindications to the use of the contrast agent (iodine allergy / untreated hypothyroidism)

• Near infra-red spectroscopy providing insufficient data to guide surgery or evidence of LVA incompatibility (As these patients will be have only just developed lymphoedema, they are by definition very early in the spectrum of disease progression. Thus, the chances of all superficial lymphatics deteriorating to the extent that LVA surgery is not possible is extremely low - <1% we expect).

• Inability to give informed consent or cooperate with assessment procedures and follow-up because of cognitive or physical impairments

• Medical co-morbidities increasing the risk of general anaesthetic (significant cardiac / respiratory disease)

• Recurrent, metastatic or progressive disease, defined by oncology team on basis of clinical assessment or imaging

• Evidence of pre-existing / primary lymphoedema on clinical history or lymphoscintigraphy

Related Conditions & MeSH terms

• Breast Cancer
• Breast Cancer Lymphedema
• Breast Neoplasms
• Lymphedema

Intervention

Procedure:
• Lymphaticovenous anastomosis surgery combined with near infrared spectroscopy imaging
Lymphoedema is well recognized as a chronic debilitating disease resulting from an abnormal collection of protein-rich fluid within the subcutaneous tissues of the body. Given the need to identify more effective treatments, more recent advances in super microsurgical techniques have seen the introduction of new procedures, perhaps the most successful of which have involved re-routing the lymphatic fluid by using microsurgery to divert small lymphatic channels into venules in the sub-dermal plane (LVA surgery). This procedure is performed under regional or general anaesthetic as a day-case operation, leaving only a few very short scars in the skin of the arm or leg.

Locations

Country	Name	City	State
United Kingdom	Mark Brandon-Grove	London
United Kingdom	Mark Brandon-Grove	Sutton	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean excess volume reduction - compared between two cohorts	Primary outcome measure is to evaluate the efficacy of LVA surgery (combined with CGT) by comparison of arm volume measurements across both the surgical and the control group at set time points post-surgery). This will be performed using the mean excess volume reduction (EVR) as a percentage change at 12 months - measured with perometry.	12 months from recruitment
Secondary	Safety - infection and surgical complications	Assess the safety of LVA surgery (supported by PDE imaging guidance) by recording incidence of infection and post-operative complications.	12 months from recruitment
Secondary	Bio-impedance spectroscopy	Compare changes in bio-impedance spectroscopy during the period of the study	12 months from recruitment
Secondary	Cellulitis	Compare the incidence of cellulitis in both groups within the 12-month study period	12 months from recruitment
Secondary	Quality of life - LYMQOL score	Compare longer term Quality of Life (QOL) in both groups using a quality of life assessment tool for lymphoedema of the limbs (LYMQOL) completed by patients. Multiple questions covering function, appearance, symptoms and mood are asked, with a quality of life score for each between 1 and 4. Total score 16 (higher score = poorer quality of life)	12 months from recruitment
Secondary	Compliance	Compliance with use of compression therapy during the study.	12 months from recruitment