Cost-Effectiveness of perioperative Vaginally Administered estrogen in postmenopausal women undergoing prolapse surgery (EVA trial): study protocol for a multicenter double-blind randomized placebo-controlled trial.

BACKGROUND: Surgery for pelvic organ prolapse (POP) is associated with high recurrence rates. The costs associated with the treatment of recurrent POP are huge, and the burden from women who encounter recurrent POP, negatively impacts their quality of life. Estrogen therapy might improve surgical outcome for POP due to its potential beneficial effects. It is thought that vaginal estrogen therapy improves healing and long-term maintenance of connective tissue integrity. Hence, this study aims to evaluate the cost-effectiveness of perioperative vaginal estrogen therapy in postmenopausal women undergoing POP surgery. METHODS: The EVA trial is a multi-center double-blind randomized placebo-controlled trial conducted in the Netherlands comparing the effectiveness and costs-effectiveness of vaginal estrogen therapy. This will be studied in 300 postmenopausal women undergoing primary POP surgery, with a POP-Q stage of ≥ 2. After randomization, participants administer vaginal estrogen cream or placebo cream from 4 to 6 weeks preoperative until 12 months postoperative. The primary outcome is subjective improvement of POP symptoms at 1 year follow-up, measured with the Patient Global Impression of Improvement (PGI-I) scale. Secondary outcomes are POP-Q anatomy in all compartments, re-interventions, surgery related complications, general and disease specific quality of life, sexual function, signs and complaints of vaginal atrophy, vaginal pH, adverse events, costs, and adherence to treatment. Follow up is scheduled at 6 weeks, 6 months and 12 months postoperative. Data will be collected using validated questionnaires and out-patient visits including gynecological examination performed by an independent gynecologist. DISCUSSION: This study investigates whether perioperative vaginal estrogen will be cost-effective in the surgical treatment of POP in postmenopausal women. It is hypothesized that estrogen therapy will show a reduction in recurrent POP symptoms and a reduction in reoperations for POP, with subsequent improved quality of life among women and cost savings. Trial registrationNetherlands Trial Registry: NL6853; registered 19-02-2018, https://www.trialregister.nl/trial/6853 . EudraCT: 2017-003144-21; registered: 24-07-2017.

Evaluation of two vaginal, uterus sparing operations for pelvic organ prolapse: modified Manchester operation (MM) and sacrospinous hysteropexy (SSH), a study protocol for a multicentre randomized non-inferiority trial (the SAM study).

BACKGROUND: Pelvic organ prolapse (POP) affects up to 40% of parous women which adversely affects the quality of life. During a life time, 20% of all women will undergo an operation. In general the guidelines advise a vaginal operation in case of uterine descent: hysterectomy with uterosacral ligament plication (VH), sacrospinous hysteropexy (SSH) or a modified Manchester operation (MM). In the last decade, renewed interest in uterus sparing techniques has been observed. Previous studies have shown non-inferiority between SSH and VH. Whether or not SSH and MM are comparable concerning anatomical and functional outcome is still unknown. The practical application of both operations is at least in The Netherlands a known cause of practice pattern variation (PPV). To reveal any difference between both techniques the SAM-study was designed. METHODS: The SAM-study is a randomized controlled multicentre non-inferiority study which compares SSH and MM. Women with symptomatic POP in any stage, uterine descent and POP-Quantification (POP-Q) point D at ≤ minus 1 cm are eligible. The primary outcome is the composite outcome at two years of absence of prolapse beyond the hymen in any compartment, the absence of bulge symptoms and absence of reoperation for pelvic organ prolapse. Secondary outcomes are hospital parameters, surgery related morbidity/complications, pain perception, further treatments for prolapse or urinary incontinence, POP-Q anatomy in all compartments, quality-of-life, sexual function, and cost-effectiveness. Follow-up takes place at 6 weeks, 12 and 24 months. Additionally at 12 weeks, 6 and 9 months cost-effectiveness will be assessed. Validated questionnaires will be used and gynaecological examination will be performed. Analysis will be performed following the intention-to-treat and per protocol principle. With a non-inferiority margin of 9% and an expected loss to follow-up of 10%, 424 women will be needed to prove non-inferiority with a confidence interval of 95%. DISCUSSION: This study will evaluate the effectiveness and costs of SSH versus MM in women with primary POP. The evidence will show whether the existing PPV is detrimental and a de-implementation process regarding one of the operations is needed. TRIAL REGISTRATION: Dutch Trial Register (NTR 6978, http://www.trialregister.nl ). Date of registration: 29 January 2018. Prospectively registered.