Abstract
Background: In the 21st century, tubal ectopic pregnancies (EPs) are diagnosed earlier in their natural history due to transvaginal ultrasound technology. More women are haemodynamically stable and therefore can be offered non-invasive outpatient management with systemic Methotrexate (MTX). However there is no evidence that MTX is necessary in all these early EPs, as many may resolve spontaneously in the absence of any treatment. To date there are no published randomized trials comparing systemic MTX with a placebo. The aim of this study is to verify if MTX is more effective than the placebo in women with tubal EP and rising/plateauing serum human chorionic gonadotrophin (hCG) levels.
Methods/Design: This is a multi-centre double-blind randomized controlled trial conducted in Australia. Haemodynamically stable women with a confirmed ultrasound diagnosis of tubal EP and a rising/plateauing serum hCG <1500 IU/L are eligible for the trial. Women with a declining serum hCG, hCG>1500 IU/L at 48hrs, viable tubal EP, severe abdominal pain, evidence of haemoperitoneum on ultrasound, diagnostic uncertainty, non-tubal ectopic pregnancy, or women with contraindications to MTX will be excluded. Systemic MTX in a single dose intramuscular regimen (50mg/m2) is compared to an identical placebo in an outpatient setting. All women will attend for a serum hCG measurement on day 4. Provided patients are haemodynamically stable, they will attend for another blood test on day 7. If a decline in serum hCG > 15% between days 4 - 7 is observed, weekly blood tests will be scheduled until undetectable hCG levels. If serum hCG levels increase or decrease < 15% between days 4 - 7, a second dose of MTX will be given and weekly blood tests will be scheduled until undetectable serum hCG. If any increase in serum hCG > 15% between days 4 - 7 or at any subsequent follow-up, women will be treated with MTX.
Primary outcome measure is treatment success, defined as uneventful decline of serum hCG to an undetectable level (<5 IU/L) by the initial intervention. Secondary outcome measures are re-interventions (additional systemic MTX injections and/or surgery for haemodynamic instability/trophoblast persistence), treatment complications and length of follow-up.
Discussion: This trial will clarify the actual effectiveness of MTX in haemodynamically stable women with an early tubal EPs and rising or plateauing hCG.
Keywords: Ectopic pregnancy, methotrexate, placebo, transvaginal ultrasound, randomized controlled trial.
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Applied Drug Research, Clinical Trials and Regulatory Affairs
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