Table 1 The PRE-EMPT trial protocol summary
Design | A randomised, pragmatic multicentre trial with integrated economic evaluation |
|---|---|
Setting | Up to 40 NHS hospitals within the UK |
Target population | Women of reproductive age, who are undergoing laparoscopy to investigate whether their pelvic pain is due to endometriosis |
Exclusion criteria | Current infertility, immediate plans to conceive |
Health technologies assessed | The main comparison is long-acting reversible contraception (LARC) versus combined oral contraceptive pill (COCP). Participants can have a pre-randomisation choice of LARC (or alternatively one will be randomly allocated): i) Levonorgestrel-releasing intra-uterine system (LNG-IUS) (fitted by a gynaecologist) or ii) 3 monthly depot medroxyprogesterone acetate (DMPA) injections (administered by the patient’s gynaecologist or general practitioner); subcomparisons will be stratified by this choice |
Outcomes | The primary outcome is the recurrence of symptoms as evaluated by the pain domain of the Endometriosis Health Profile–30 (EHP-30) questionnaire at 36 months post-randomisation. The EHP-30 is a validated, responsive health-related quality of life measure for endometriosis. It will also be assessed prior to randomisation and at 6, 12 and 24 months. Secondary outcomes: • All other symptom and quality of life (QoL) domains of the EHP-30 • Non-menstrual pelvic pain and dysmenorrhea measured by 0–100 visual analogue (VAS) pain scale • Fatigue, as measured by the Fatigue Severity Score • Menstrual regularity • Generic QoL (EQ-5D) and capabilities, as measure of wellbeing (ICE-CAP) • Further diagnostic and therapeutic surgery for endometriosis (as a proxy for recurrence) • Discontinuation rates of randomised treatment, with reasons for change, serious adverse events • Cost per quality-adjusted life year (QALY) and cost per change in symptom score. • An increased knowledge of issues identified as important by the participants regarding their treatment and its impact on their lives |
Analysis | The main comparison will be LARC vs COCP, with sub-comparisons of the groups where the intention is to treat with either LNG-IUS or DMPA if randomised to LARC. The primary outcome will be analysed using a linear regression model including a variable for each treatment group and including baseline score and the minimisation factors as covariates. Effect sizes will be presented as point estimates and 95% confidence intervals. Standard statistical methods will be used for other outcomes. All analysis will be by intention to treat. |
Sample | The study will have 90% power (p = 0.05) to detect an 8-point difference in the main comparison assuming the standard deviation of the EHP-30 pain domain is 22 points. This will require 160 women per group, 320 in total. To account for 20% loss to follow-up, this target has been inflated to 400 women in total |