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

RESEARCH QUESTION:

What is the effectiveness of laparoscopic treatment of isolated superficial peritoneal endometriosis (SPE) to manage endometriosis-associated pain? BACKGROUND:

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.

DESIGN:

A multi-centre, participant-blind, parallel-group randomised controlled clinical and cost effectiveness trial with internal pilot. SETTING: UK gynaecology departments. TARGET POPULATION:

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. ELIGIBILITY CRITERIA:

Women in whom laparoscopy reveals isolated SPE, defined as SPE without concomitant ovarian endometrioma or deep endometriosis. HEALTH TECHNOLOGIES BEING ASSESSED: Laparoscopic ablation and / or excision of SPE, technique determined by the surgeon. OUTCOME MEASURES: Primary outcome measure -

Condition specific quality of life at 12 months post randomisation assessed using the pain domain of the Endometriosis Health Profile 30 (EHP-30). Secondary outcome measures -

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.

Economic outcome measure -

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. SAMPLE SIZE:

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%. Timeline (months): -4 – 0 Prepare protocols, ethics submission, etc (pre-award)

-4 – 3 Restart ESPRiT1 recruitment (1 September 2020) 1 – 3 Start up 4 – 18 Internal pilot (46 sites) 19 – 24 Continue opening sites and recruitment (total 70 sites) 25 – 37 Complete recruitment 38 – 49 Follow up 50 – 54 Analysis/closeout ANTICIPATED IMPACT AND DISSEMINATION:

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.