Mifepristone and Letrozole versus methotrexate for treatment of Ectopic pregnancy - a randomized, controlled non-inferiority trial (MILE).

Our aim is to develop a safe and effective medical treatment for Ectopic Pregnancy (EP). EP occurs in 1-2% of pregnancies and is the leading cause of death in Ist trimester pregnancy. Prompt diagnosis and treatment is needed to avoid morbidity and mortality.

Treatment options are surgery or systemic methotrexate (MTX), used off label, associated with rare but severe side effects, teratogenicity and impaired future fertility. There is an increasing demand for a safe medical option.

Preventing estradiol and progesterone synthesis/action by combining mifepristone and letrozole (MILE) may result in resolution of the EP.

We hypothesize that efficacy of MILE is non-inferior to MTX (primary outcome) at 85% with a non-inferiority margin set at 10%. 400 patients are needed to obtain a power of 80%.Objectives: To evaluate efficacy, safety, acceptability of MILE or MTX and impact on fertilityPatients: Women with EP fulfilling eligibility criteria randomized 1:1 toIntervention: MILE orControl: MTXPrimary outcome: The proportion of patients with successful treatment defined as a decline in serum hCG to < 2 IU/L without the need for any additional medical or surgical intervention within 60 days of treatment.

Other outcomes: AEs, time to resolution, subsequent pregnancy.The results will guide the implementation of a new EP treatment with increased safety, flexibility, reduced costs and less impact on future fertility. There is a global need for evidence based safe treatment options for EP.