Comparing Two Medical Treatments for Early Pregnancy Failure.

Mifepristone and Misoprostol Versus Misoprostol Alone for Uterine Evacuation After Early Pregnancy Failure: a Randomized Double Blind Placebo-controlled Comparison (Triple M Trial)

This study aims to compare whether a combination of two drugs (Mifepristone and misoprostol) are superior compared to using only one of these drugs (Misoprostol) as medical treatment for a miscarriage. Women in whom early pregnancy failure, 6-14 weeks postmenstrual, is ultrasonographically confirmed qualify for this study.

It is expected that the combination of Mifepristone and Misoprostol is more effective in reaching complete evacuation, and therefore can prevent more invasive treatment such as curettage.

This study will test the hypothesis that, in early pregnancy failure, the sequential combination of mifepristone with misoprostol is superior to the use of misoprostol alone in terms of complete evacuation of products of conception (primary outcome), patient satisfaction, complications, side effects and costs (secondary outcomes). The trial will be performed multi-centred (hospitals), prospectively, two-armed, randomized, double-blinded and placebo-controlled.

Women with ultrasonographically confirmed early pregnancy failure (6-14 weeks postmenstrual), managed expectantly for at least one week, can be included. Before medical treatment with misoprostol (two doses 400mcg (four hours apart), repeated after 24 hours if no tissue is lost), patients will be randomized to oral mifepristone (600mg) or oral placebo (identical in appearance). The investigators aim to randomize 460 women in a 1:1 ratio, stratified by centre.

After six weeks, the primary endpoint, complete or incomplete evacuation, will be determined

Inclusion Criteria:

Early pregnancy failure, 6-14 weeks postmenstrual with

• a crown-rump length ≥ 6mm and no cardiac activity OR

• a crown-rump length <6mm and no fetal growth at least one week later OR

• a gestational sac with absent embryonic pole for at least one week.

  • At least one week after diagnosis OR a discrepancy of at least one week between crown-rump length and calendar gestational age
  • Intra-uterine pregnancy
  • Women aged above 16 years
  • Hemodynamic stable patient
  • No signs of infection
  • No signs of incomplete abortion
  • No contraindications for mifepristone or misoprostol

Exclusion Criteria:

• Patient does not meet inclusion criteria, discovered after randomization
• Inability to give informed consent
• Known clotting disorder or use of anticoagulants
• Known risk factors for, or presence of, a cardiovascular disease
• Language barrier