Does self-administered vaginal misoprostol result in cervical ripening in postmenopausal women after 14 days of pre-treatment with estradiol? Trial protocol for a randomised, placebo-controlled sequential trial

Abstract

Objective: To compare the impact of 1000 micrograms of self-administered vaginal misoprostol versus self-administered vaginal placebo on preoperative cervical ripening after pre-treatment with estradiol vaginal tablets at home in postmenopausal women prior to day-care operative hysteroscopy.

Design: Randomised double-blind placebo-controlled sequential trial. The boundaries for the sequential trial were calculated on the primary outcomes of a difference of cervical dilatation > or = 1 millimetre, with the assumption of a type 1 error of 0.05 and a power of 0.95.

Setting: Norwegian university teaching hospital.

Population: Postmenopausal women referred for day-care operative hysteroscopy.

Methods: The women were randomised to either 1000 micrograms of self-administered vaginal misoprostol or self-administered vaginal placebo the evening before day-care operative hysteroscopy. All women had administered a 25-microgram vaginal estradiol tablet daily for 14 days prior to the operation.

Main outcome measures: Preoperative cervical dilatation (difference between misoprostol and placebo group, primary outcome), difference in dilatation before and after administration of misoprostol or placebo, number of women who achieve a preoperative cervical dilatation > or = 5 millimetres, acceptability, complications and side effects (secondary outcomes).

Results: Intra-operative findings and distribution of cervical dilatation in the two treatment groups: values are given as median (range) or n (%). Difference in dilatation before and after administration of misoprostol and placebo: values are given as median (range) of intraindividual differences. Percentage of women who achieve a cervical dilatation of > or = 5 mm, percentage of women who were difficult to dilate. Acceptability in the two treatment groups: values are given as completely acceptable n (%), fairly acceptable n (%), fairly unacceptable n (%), completely unacceptable n (%). Pain in the two treatment groups: pain was measured with a visual analogue scale ranging from 0 (no pain) to 10 (unbearable pain): values are given as median (range). Occurrence of side effects in the two treatment groups. Values are given as n (%). Complications given as n (%).

Funding sources: No pharmaceutical company was involved in this study. A research grant from the regional research board of Northern Norway has been awarded to finance Dr K.S.O.'s leave from Hammerfest hospital as well as travel expenses between Hammerfest and Oslo, and research courses. The research grant from Prof B.I.N. (Helse Øst) funded the purchase of estradiol tablets, the manufacturing costs of misoprostol and placebo capsules from the hospital pharmacy, as well as the costs incurred for preparing the randomisation schedule and distribution of containers containing capsules to hospital. Prof B.I.N.'s research grant also funded insurance for the study participants.

Conclusions: Estimated completion date 31 December 2008.

Figure 1

Continuation region of the sequential test. The stopping boundaries are shown. H0, boundary for the null hypothesis, HA, boundary for the alternative hypothesis.

Figure 2

Flow diagram.