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Health Technol Assess. 2015 Oct;19(88):i-xxv, 1-118. doi: 10.3310/hta19880.

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial.

Collaborators (194)

Kulshrestha RP, Kulshrestha S, O'Brien K, Coulson W, Craig J, Descals L, Kownacki A, Montague E, McKenzie B, Spooner CA, Sanganee N, Collier IP, Cope SJ, Goodwin A, Sheldrake LJ, Hanly C, Rajesh R, Hutchon S, Bingham T, Gupta JK, Ingram J, Ingram L, Soneja H, Pettinger R, Sadler C, Brown M, Chaffey J, Cowan V, Brain L, Pabla HS, Godridge H, Horner ME, Horton PD, McGhee MF, McGrath M, Sumner KR, Ward-Campbell GJ, Williams S, Madhavan P, Brewin L, Glenchcliffea A, Young DJ, Heslington K, Hunt D, Saikia-Varman N, Jones M, Kavi L, Kidd L, Kai J, Ladha K, Morris M, O'Neill K, Patel JN, Waddell JE, Beighton PG, Cole FH, Edwards RM, Thompson A, Ayres J, Davies J, Poltock TL, Smith M, Talbot H, Cuthbert AJ, Horwell S, Jenkins C, Sinha G, Weaver K, Goodwin B, Patel RP, Debenham SE, Cartmill AD, Parker S, Pennington E, Pennington SJ, Young GB, Butler S, Hamilton PA, Warhad L, Elliott J, Lawrence E, North J, Elliott CI, Jerome S, Shipman PA, Bagchi R, Sheerin N, Blackwall C, Divers V, Siddall J, Parle HJ, Read S, Patodi SK, Amis S, Moloney S, Leung HH, Obi HU, Sidhu M, Ahmed N, Carter SR, Davies W, Harvey H, Khanna K, Rice PF, Shapiro L, Stone J, Parkin T, Craig JM, Moss PJ, Steele V, Cartwright JE, Edward MG, Harrison C, Francis R, Hassall P, Lloyd CE, Haynes J, Budh-Raja S, Budh-Raja VP, Patel SP, Redferne JH, Deb S, Lancaster A, Powell MC, Wragg J, O'Brien DC, Milner S, Taylor DW, Davies D, Tangri AK, Tangri C, Amer S, Prileszky G, Warlow C, Whatmough P, Duncan CH, Bower W, Irani S, Rajput S, Rajput VK, Young K, Cooper RE, Chin K, Scott D, Stacey J, Dadd C, Joshi KG, Sundar K, Broomhead RM, Clarke MP, Sangha E, Wood J, Fitzgerald-Jones B, Harley-Mason GR, Coward AD, Coward CM, Pash J, Little HM, Macdonald AG, Williams JP, Marshall J, McBride H, Watson KA, Clay SN, Walker SA, Billington J, Griffiths H, Mehta R, Emslie CJ, Bath SS, Chiam W, Gordon KR, Latthe M, Nandi DK, Lilford VA, Smith G, Godfrey E, Griffiths S, Porter C, Baird MS, Crombie C, O'Donnell D, Horton V, Kelsey RE, Fletcher JD, Hall F, Lenton C, Allen MP, Heanue J, McDonnell JH, Hancock J, Pattni BL, Banerjee ST, Pate S.

Author information

School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
Birmingham Women's Hospital NHS Foundation Trust, Edgbaston, Birmingham, UK.
Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK.
School of Health and Life Sciences, Aston University, Birmingham, UK.
Division of Primary Care, University of Nottingham, Nottingham, UK.
Health Economics Unit, University of Birmingham, Birmingham, UK.
Clinical Trials Service Unit, University of Oxford, Oxford, UK.



Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited.


To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena®, Bayer) compared with usual medical treatment, with exploration of women's perspectives on treatment.


A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study.


Women who presented in primary care.


A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment.


LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment.


The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses.


The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI -0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women's experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments.


The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women's assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause.


Current Controlled Trials ISRCTN86566246.


This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information.

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