Mifepristone and misoprostol versus misoprostol alone for uterine evacuation after early pregnancy failure: a pilot study

Early pregnancy failure (EPF) is a common complication of pregnancy. Yearly in
the Netherlands, 10.000 women with EPF do not abort spontaneously and do
receive medical or surgical treatment in order to remove the products of
conception from the uterus. For many years, surgical treatment (dilatation and
curettage) has been the standard treatment. However, medical treatment is a
safer and less expensive alternative. Misoprostol (synthetic prostaglandin E1
analogue) is used as standard medical treatment. Unfortunately, the current
medical treatment with misoprostol only has a 54% complete evacuation rate
without additional surgery. Medical treatment for EPF can most probably be
improved. For other conditions, such as medical termination of vital pregnancy,
the combination of mifepristone with misoprostol has been shown to be superior
to the use of misoprostol alone. The superiority of the combination has also
been demonstrated for induction of labour in case of fetal death after the
first trimester. Therefore, it is reasonable to believe that, also for early
pregnancy failure, mifepristone with misoprostol will be superior to
misoprostol alone. Based on retrospective data in the Radboudumc Hospital (a
pilot study) that are compatible with data from the literature, we expect a
complete evacuation rate of at least 67%. However, until now conclusive
evidence is lacking. A randomized, double blind placebo-controlled trial is
required to test the hypothesis that in early pregnancy failure the sequential
combination of mifepristone with misoprostol is superior to the use of
misoprostol alone.

Th**is study will compare sequential mifepristone and misoprostol (*M&M*)
treatment versus misoprostol treatment alone, which is currently the standard
medical treatment in the Netherlands.

The trial will be conducted prospectively, two-armed, randomized,
double-blinded and placebo-controlled.

After randomization at day 1 :

- Mifepristone 600mg in the intervention group
- placebo in the control group

followed by the standard treatment with misoprostol : two doses of 400ug orally
at day 3 and 4.

We intend to compare medical treatments that are already applied worldwide for
several other indications. No additional physical examination is needed for
this study, nor will extra blood be taken from the subjects. Study participants
will receive information and will be asked to fill in questionnaires at three
different time points. Participants are followed in an outpatient clinic;
hospital admission is possible at all times. We do not expect additional risks
or benefits.