Ureteric identification using Indocyanine green dye versus Conventional ureteric stenting to reduce post-operative pain and surgical morbidity during Endometriosis surgery: A pilot trial (ICE trial)

Research question Is it feasible to run a full-scale, multicentre, randomised controlled trial (RCT) that would compare injection of indocyanine green (ICG) with ureteric stenting, as a means of identifying the ureters during laparoscopic excision of deep endometriosis, in terms of post-operative pain, safety and cost-effectiveness?

Background Endometriosis affects 1 in 10 women of reproductive age, causing symptoms including chronic pain and infertility. Deep endometriosis (DE) is more severe, extending deeper into the pelvis, beyond the peritoneum.

Surgical excision of endometriosis requires identification and careful dissection of retroperitoneal pelvic structures, notably the ureter. Inadvertent ureteric injury causes major morbidity for the patient.

Ureteric stents, sited intraoperatively via cystoscopy to allow ureter identification, are typically removed after 2-4 weeks, but commonly cause significant pain and haematuria during this period.

A novel technique of intraoperative cystoscopic ureteric catheterisation involving retrograde injection of indocyanine green (ICG), a fluorescent dye, into the ureter allows the fluorescing ureter to be visualised laparoscopically.

This may allow safer, more thorough dissection of the pelvic sidewall without the morbidity associated with ureteric stenting. However, there is currently only limited evidence to support this technique.

Aims and Objectives Assess our ability to recruit to the study Assess the willingness of surgeons to randomise patients Create appropriate patient information, suitable for a subsequent main trial Test the ability to capture outcome data and assess the rate of drop-out Test the ability to collect health economic data; use decision modelling to test value of obtaining further information in this area Assess acceptability of the trial to participants Estimate parameters required for a sample size calculation for a main trial We will recruit 70 patients with DE, from a range of backgrounds, who are due to undergo minimally invasive resection of endometriosis (with or without hysterectomy) that would require interoperative ureteric stenting, from two endometriosis centres in the UK.

After enrolment, baseline data will be collected, including demographics, pain and quality of life.

Patients will be randomised 1:1 to standard care (stenting) or intervention (ICG), prior to surgery, via computer-generated randomisation.

Intraoperative data on stage of disease (ENZIAN classification), surgical time, blood loss and injury to viscera or blood vessels will be collected. Postoperative data (pain, quality of life and surgical complications) will be collected at 6 weeks and 3 months.

Four focus groups (two from each arm of the trial) of 4-6 participants, will give feedback on the experience of study participation and the acceptability of study processes.

Timelines for delivery Months 0-3: Set up Months 4-18: Recruitment Months 7-21: Follow up (3-month time point) Months 22-24: Data cleaning, analysis, preparation and submission of final report Impact and Dissemination Results will be shared with relevant stakeholders, patients, medical professionals, professional societies, patient support groups, and NHS policy makers.

Findings will be published in a major medical journal and presented at national scientific meetings.

Dissemination on the websites of health professional societies and endometriosis and pelvic pain charities, such as Endometriosis UK, will be guided by our PPI work.