Microsoft word - summary metexuk.doc

The METEX study
(Methotrexate versus Expectant management)
Methotrexate versus expectant management in women
with ectopic pregnancy
Background
The incidence of ectopic pregnancy (EP) is approximately 1-2 % of all pregnancies. An early diagnosis is possible by
transvaginal sonography (TVS) in combination with serum hCG measurements. As a consequence, the clinical
presentation of EP has changed from a life threatening disease, necessitating emergency surgery, to a more benign
condition in sometimes even asymptomatic patients for which non-surgical treatment options are available, i.e. medical
treatment or expectant management.
In the medical treatment of EP, systemic methotrexate is the drug of choice. In several randomised controlled trials
systemic methotrexate has been shown to be an effective treatment in selected patients with EP. Expectant
management has been practiced, based on the acknowledgement that the natural course of many early EPs is a self
limiting process, ultimately resulting in tubal abortion or reabsorption. For both treatment regimens follow up of serum
hCG is mandatory to detect impending treatment failure.
Ten percent of women presenting with suspected EP have low and plateauing serum hCG concentrations. These
women are often treated with systemic methotrexate. However, there is no evidence on the effects of treatment in this
particular subgroup of women
Objective
To study whether in women with EP with low but plateauing serum hCG concentrations treatment with systemic
methotrexate in a single dose intramuscular regimen is superior over expectant management in terms of treatment
success, future pregnancy, health related quality of life and costs.

Study-design
Multicenter randomised controlled trial in four participating centers in The Netherlands.

Population
All hemodynamically stable patients ≥ 18 years with either on TVS a visible EP and a plateauing serum hCG
concentration < 1,500 IU/L or with a pregnancy of unknown location (PUL) and a plateauing serum hCG concentration
< 2,000 IU/L (persisting PUL) will be eligible for the trial. Patients with a viable EP, signs of tubal rupture or active intra
abdominal bleeding, or a contra-indication for methotrexate will not be included. Randomisation will be carried out by
an internet based randomisation.

Intervention and follow up
Systemic methotrexate in a single dose intramuscular regimen (1 mg/kg body weight) will be compared with expectant
management in an outpatient clinical setting. Serum hCG levels will be monitored weekly. In case of inadequately
declining serum hCG concentrations and/or clinical symptoms treatment (methotrexate or surgery) will be installed.
Quality of Life will be assessed before, during and after treatment by questionnaires. Future fertility will be assessed by
questionnaires after 6, 12, 18 and 24 months.

Outcome measures and analysis
The primary outcome measure is an uneventful decline of serum hCG to an undetectable level. Secondary outcomes
are number of (re)interventions (additional methotrexate and/or surgery), treatment complications, health related
quality of life, future fertility, and financial costs. The analysis wil be performed according to the intention to treat
principle. Moreover, patients' preferences will be assessed.

Estimated patient's effort and risks
In both treatment arms patients are at risk of tubal rupture and/or active bleeding. Methotrexate has possible side
effects. After methotrexate treatment patients are advised not to conceive during 3 months. Patients are requested to
fill in questionnaires to assess quality of life before, during and after treatment. Furthermore, patients will be contacted
by telephone or mail after 6, 12, 18, 24 months to assess her future fertility.
E-mail: metex@amc.uva.nl

Source: http://www.esepstudy.nl/metexwebsite/PDF/summary%20METEXUK.pdf