Title: ESPriT2: A multi-centre randomised controlled trial to determine the effectiveness of laparoscopic treatment of isolated superficial peritoneal endometriosis for the management of chronic pelvic pain in women
Funder: Chief Scientist Office, Scotland

Abstract: BACKGROUND: Endometriosis affects ~176 million women worldwide and can lead to debilitating chronic pelvic pain (CPP). In women with endometriosis, cells like those lining the uterus are found outside the uterus, commonly within the pelvis. There are three types of endometriosis: superficial peritoneal endometriosis (SPE) found on the pelvic lining and comprising 80% of all subtypes, ovarian (endometrioma) and deep. SPE is diagnosed by keyhole surgery (laparoscopy) and gynaecologists usually surgically treat it (excise and/or ablate) at the time. Unfortunately, many women do not get good pain relief from removal of SPE and some have complications from surgery. Despite thousands of surgeries annually, there is little scientific evidence as to whether surgical removal of SPE improves overall symptoms and quality of life more than not surgically treating the endometriosis, or whether surgery could exacerbate symptoms, or even cause harm._x000D_ RESEARCH PLAN: We are undertaking a large clinical trial called ‘ESPriT2’ in ~70 UK hospitals. We will randomise 400 women with CPP who have only SPE found at laparoscopy over 36 months. Women who agree to take part will be randomly allocated to have the SPE surgically removed during the laparoscopy, or not to have it removed. Neither the women, nor their gynaecologists, will be able to choose, and the women will not be told whether or not they have had the SPE removed. In this way we can make sure the women and their experiences within the two groups are similar, which will reduce the chances of obtaining incorrect (biased) results. Participants will be asked to complete questionnaires about all of their symptoms and the impact these have on their quality of life (before surgery, and at 3, 6, and 12 months, after surgery). All women will have the option of taking any of the currently recommended medical treatment options for endometriosis, such as oral painkillers or hormones, during the trial. We will also estimate the costs of the different approaches to the NHS. ESPriT2 contains an internal pilot to allow us to check whether we are on target after 24 months._x000D_ IMPACT: The information from this trial will allow women with CPP and gynaecologists to make an informed choice whether to proceed immediately to surgical removal when a diagnostic laparoscopy identifies SPE. If the trial shows that surgery does not help, or exacerbates symptoms, this would reduce the number of unnecessary operations and support the need for developing more effective methods of pain management for women with SPE._x000D_ PATIENT/PUBLIC INVOLVEMENT: Representatives from Endometriosis UK and Endometriosis Association of Ireland have contributed to this application, and will be involved throughout the trial. _x000D_ DISSEMINATION: The results will be published in medical journals, presented at medical conferences, and will feed into updates of national/international endometriosis guidelines. Information to help women decide about surgery will be prepared for patient organisations and websites.

Lay abstract: RESEARCH QUESTION:_x000D_ What is the effectiveness of laparoscopic treatment of isolated superficial peritoneal endometriosis (SPE) to manage endometriosis-associated pain?_x000D_ BACKGROUND: _x000D_ Endometriosis affects ~176 million women worldwide and can lead to debilitating pelvic pain. Three subtypes of endometriosis exist, with ~80% of women having superficial peritoneal endometriosis (SPE). Endometriosis is diagnosed by laparoscopy and, if SPE is found, gynaecologists usually remove it surgically. However, pain relief from surgical removal of SPE is often suboptimal and short lived._x000D_ DESIGN:_x000D_ A multi-centre, participant-blind, parallel-group randomised controlled clinical and cost effectiveness trial with internal pilot._x000D_ SETTING:_x000D_ UK gynaecology departments._x000D_ TARGET POPULATION:_x000D_ Women (over 16) with chronic pelvic pain (CPP), including dysmenorrhoea and/or dyspareunia, of more than 6 months duration undergoing a laparoscopy for suspected endometriosis. _x000D_ ELIGIBILITY CRITERIA:_x000D_ Women in whom laparoscopy reveals isolated SPE, defined as SPE without concomitant ovarian endometrioma or deep endometriosis._x000D_ HEALTH TECHNOLOGIES BEING ASSESSED:_x000D_ Laparoscopic ablation and / or excision of SPE, technique determined by the surgeon._x000D_ OUTCOME MEASURES:_x000D_ Primary outcome measure - _x000D_ Condition specific quality of life at 12 months post randomisation assessed using the pain domain of the Endometriosis Health Profile 30 (EHP-30)._x000D_ Secondary outcome measures -_x000D_ Specific pain symptoms and physical/emotional functioning (Rome IV Criteria, Pelvic Pain and Urgency/Frequency Patient Symptom Scale, PAINDETECT(TM), Brief Fatigue Inventory, Pain Catastrophising Questionnaire, Fibromyalgia Scale, Measure Yourself Medical Outcome Profile 2, EuroQol 5 Dimensions 5 Level Questionnaire [EQ-5D-5L], occupational outcomes (Working Productivity and Activity Impairment Questionnaire), need for further surgery or other medical treatment (e.g. analgesics, hormones) at 3, 6 and 12 months. Surgical complication rates, fertility and adverse outcome data will also be collected. _x000D_ Economic outcome measure -_x000D_ Incremental cost per quality-adjusted life year (QALY, derived from participant responses to the EQ-5D-5L) gained from a health service perspective at 12 months and modelled over the reproductive life of women. _x000D_ SAMPLE SIZE: _x000D_ For ESPriT2, we need to randomise 400 women over 36 months to detect an 8-point difference in the EHP-30 pain domain with 90% power (two-sided alpha 0.05), assuming a standard deviation of 22 points and an attrition rate of 20%. _x000D_ Timeline (months):_x000D_ -4 – 0 Prepare protocols, ethics submission, etc (pre-award)_x000D_ -4 – 3 Restart ESPRiT1 recruitment (1 September 2020)_x000D_ 1 – 3 Start up_x000D_ 4 – 18 Internal pilot (46 sites)_x000D_ 19 – 24 Continue opening sites and recruitment (total 70 sites)_x000D_ 25 – 37 Complete recruitment_x000D_ 38 – 49 Follow up_x000D_ 50 – 54 Analysis/closeout_x000D_ ANTICIPATED IMPACT AND DISSEMINATION:_x000D_ The information from this trial will allow women with CPP and gynaecologists to make an informed choice whether to proceed immediately to surgical removal when a diagnostic laparoscopy identifies SPE. Results will be disseminated via Endometriosis UK, Endometriosis Association of Ireland and Endometriosis.org, professional bodies, NHS and university websites, open access journals, clinical practice guidelines and presentations in relevant conferences.

Research activity codes: 6.4 SURGERY
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH