GEM3
Research type
Research Study
Full title
GEM3: A double blind placebo controlled trial of a combination of methotrexate and gefitinib versus methotrexate alone as a treatment for ectopic pregnancy
IRAS ID
187949
Contact name
Ann Doust
Contact email
Sponsor organisation
University of Edinburgh
Eudract number
2015-005013-76
Duration of Study in the UK
3 years, 4 months, 30 days
Research summary
Research Summary
Ectopic pregnancy (EP) occurs when an embryo implants in a Fallopian tube. A methotrexate (MTX) injection causes serum pregnancy hormone [hCG] levels to fall and is a suitable treatment for stable EP. However, in 30% of women, MTX is unsuccessful (with surgery required); and in 15%, it is partially effective (2nd dose of MTX required); and for many women, treatment is prolonged (many hospital visits). We have performed studies giving MTX and gefitinib (lung cancer drug) to women with EP. We found that giving MTX and gefitinib together may reduce the need for surgery and hospital visits without causing any important side effects. These findings now require further study in a large trial and we need to understand how gefitinib works. We plan a clinical trial (‘main study’) to compare MTX and either a seven-day course of gefitinib or placebo (dummy) tablets. We will assess whether the two drugs together are better at treating the EP without the need for surgery; reducing hCG levels, hospital visits and need for further MTX; and look at safety and patient satisfaction. Treatment response will be monitored according to local standard protocols. The study will recruit 328 women from ~50 UK hospitals. To examine how MTX and gefitinib affects the pregnancy tissue (‘mechanistic study’), we will also 30 women who opt to have their EP treated surgically to take medication pre-operatively (gefitinib and MTX) and collect their EP tissues at time of surgery. We will also ask women in whom the treatment has failed and who require ‘rescue’ surgery for permission to collect their pregnancy tissues. Lastly, we plan to collect a blood sample from all women entering the trial to test for evidence of past exposure to chlamydial infection to determine whether this is a risk factor for EP.
Summary of Results
What was the question?
A tubal ectopic pregnancy is where a fertilised egg is not growing in the womb. The pregnancy cannot be saved and the woman is at risk of losing her Fallopian tube and if this pregnancy is left to grow can even die. Current treatment is with methotrexate or surgery (an operation can happen because the ectopic pregnancy has ruptured and caused internal bleeding, because the medical treatment has not worked and the ectopic pregnancy needs to be removed or the patient can chose to have an operation). However, methotrexate treatment can fail in approximately 30% of women. We carried out research to see if the addition of a new drug (gefitinib, a drug used for lung cancer) to methotrexate could lower the number of women needing an operation to remove their ectopic pregnancy.
What did we do?
We involved 328 women with a stable tubal ectopic pregnancy, who were being treated medically with methotrexate, and randomly assigned them to have methotrexate alone or a combination of methotrexate and gefitinib. The gefitinib was taken in tablet form for seven days, and the methotrexate was given as an injection. We followed the women up in line with their clinical care until their ectopic pregnancy resolved or they had surgery to remove the ectopic pregnancy.
What did we find?
The addition of gefitinib to methotrexate did not reduce the number of women who required surgery to remove their ectopic pregnancy. More women taking gefitinib experienced side effects such as a facial rash or diarrhoea.
What does this mean?
Treatment with methotrexate remains the only medical treatment option for ectopic pregnancy. More research is needed.REC name
Scotland B REC
REC reference
16/SS/0014
Date of REC Opinion
29 Feb 2016
REC opinion
Further Information Favourable Opinion