A feasibility multicentre randomised controlled trial on miCRosurgical immediate lYmPhaTIC reconstruction to reduce risk of lymphoedema (CRYPTIC trial)

Research question To assess the feasibility of conducting a randomised controlled trial (RCT) to evaluate immediate lymphatic reconstruction (ILR) in the prevention of lymphoedema following axillary lymph node clearance (ALNC). Background Lymphoedema is a chronic and progressive disease leading to swelling of soft tissue due to failure of drainage of lymphatic fluid. It has a significant impact on patients quality of life, affecting at least 100,000 patients in the UK alone. Lymphoedema of the upper limb occurs in about 25% of patients who undergo ALNC for breast or skin cancer which is performed to prevent cancer spread. ALNC involves removal of all lymphatic tissue in the armpit, which can result in lymphatic fluid becoming trapped in the arm and hence causing upper limb swelling (the current Standard of Care). ILR is reported to reduce incidence of lymphoedema following ALNC. The ILR procedure involves a microsurgical technique to anastomose the disconnected lymphatic vessels to adjacent veins to bypass an area that is devoid of lymphatic drainage and re-establish the lymphatic flow. Early results are promising, however there remains a paucity of high-quality evidence to support its wider adoption. Hence, only limited centres and selected surgeons offer this procedure to patients undergoing ALNC. Aims and objectives To evaluate the feasibility of conducting a RCT comparing ILR against the current standard of care in prevention of lymphoedema following ALNC. We will evaluate the ability to recruit, randomise and retain patients in the study. Methods Multi-centre, longitudinal, parallel arm, double blinded RCT to evaluate the efficacy of ALNC with ILR (intervention) versus ALNC without ILR (control). The target population is patients with breast cancer or skin cancer of the trunk undergoing oncological resection and ALNC. Five centres across England and Wales will be recruiting into the trial to enrol a total of 50 patients over 18 months. Group allocation will be determined by individual patient randomisation using random permuted blocks. Patients, statisticians and outcome assessors will be blinded to group allocation. Timelines for delivery A 6-month set-up period will be required, followed by 18 months of recruitment. The first 10 patients will be followed up for 24 months, subsequent 10 patients for 18 months and the subsequent 10 patients for 12 months. The remaining patients will be followed up for 6 months. The variable follow-up duration is to evaluate the feasibility of using different follow up periods in a subsequent definitive study if indicated. A further 2 months will be spent on data cleaning and 4 months on data analysis, write up and dissemination. Overall study duration is 36 months. Anticipated impact and dissemination The findings of this feasibility study will inform a future definitive RCT (if indicated) to evaluate the efficacy of ILR in preventing lymphoedema following ALNC. The findings of the study will be disseminated through trial registers, conferences, peer-reviewed journals, patient information websites, specialist surgical societies and social media networks which will be informed by patient and public involvement (PPI) input.