Randomized Controlled Trial on Use of Letrozole in the Medical Management of Tubal Ectopic Pregnancies
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Treatment success
研究概览
简要总结
This is a multi-centred randomized controlled trial on the addition of letrozole in the medical management of tubal ectopic pregnancies.
Tubal ectopic pregnancies are abnormal pregnancies in the Fallopian tube, rather than in the womb. They occurred in around 1-2% of all pregnancies. Methotrexate (MTX) given by the intramuscular route i.e. systemic, a commonly used drug for cancer , was a widely used alternative for management for unruptured tubal ectopic pregnancies and was recommended as first line treatment for selected women.
Letrozole, aromatase inhibitor, can suppose oestradiol level. Combination of letrozole with misprostol has shown to improve the complete abortion rate in miscarriage. As a result, addition of letrozole may cause a higher success rate in the medical treatment of ectopic pregnancy.
As the evidence of combination of MTX and letrozole in tubal ectopic pregnancies is not available, the objective of the present study is to evaluate the efficacy of combination of MTX and letrozole compared to MTX alone in women with tubal ectopic pregnancies.
详细描述
Tubal ectopic pregnancies occur in around 1-2% of all pregnancies. Traditionally, surgery with salpingectomy was the mainstay of treatment; however, it comes with anaesthetic and operatives risks in addition to an increased cost for operative procedures. In recent years, systemic methotrexate (MTX), a dihydrofolate reductase inhibitor, has been a widely used alternative for management for unruptured tubal ectopic pregnancies. The success rate of systemic MTX at a doses of 50mg/m2 body surface area is around 70% which ranges from 65 to 95%, depending greatly on the level of human chorionic gonadotrophin (hCG), the size of adnexal mass and presence of fetal heart pulsation.
Use of systemic MTX as the first-line management has been proposed for women with unruptured ectopic pregnancy where the adnexal mass is smaller than 35mm, serum hCG level is less than 5000 IU/l and fetal heartbeat is absent.
Letrozole is a third generation non-steroidal reversible aromatase inhibitor. It can suppress oestradiol level up to 95% to 99% after administration according to pharmacodynamics and pharmacokinetics studies. Oestrogen is important in the support of early pregnancy, other than progesterone with well-known pivotal effect on the maintenance of early pregnancy.
Animal studies showed the combination of mifepristone and letrozole worked synergistically and induced almost 100% termination of pregnancies in rats. Letrozole induced 50% miscarriage rate in pregnant baboons. Letrozole combined with vaginal misoprostol regimen was associated with a higher complete abortion rate than misoprostol alone in pregnancies up to 63 days.
The use of letrozole in ectopic pregnancy has never been explored. It is hypothesized that letrozole can suppress serum oestradiol level, which in turn, may cause failure of pregnancy in ectopic pregnancy. The aim of this study is to investigate the clinical effectiveness of letrozole in addition to MTX in the medical treatment of ectopic pregnancy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The identical looking placebo will be given. A computer generated sequence will be created. The sequence will be sealed in consecutively concealed opaque envelopes. Both the participant/ care provider/ investigator and outcomes assessor will blinded to the group assigned.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Presence of heterogenous adnexal mass on USG suggestive of tubal ectopic pregnancy with hCG level >=1500 IU/L and <= 5000 IU/L
- •Absence of fetal heart pulsation
- •Mean diameter of adnexal mass <= 3.5cm
- •Haemodynamically stable
- •No significant abdominal pain
排除标准
- •Presence of significant amount of free fluid in pelvis
- •Allergic to MTX
- •Deranged liver function test (AST/ ALT or GGT >= 2 upper limit of normal)
- •Deranged renal function test (eGFR <= 45ml/min)
- •Heterotopic pregnancies
研究组 & 干预措施
Letrozole
Participants will be given letrozole 10mg daily for one week after standard medical management for tubal ectopic pregnancy by methotrexate injection. Subsequently they will receive the standard management for medical management of tubal ectopic prengnacies.
干预措施: Letrozole tablets (Drug)
Placebo
Participants will be given identical looking placebo for one week and receive the same standard management for medical management of tubal ectopic pregnancies.
干预措施: Placebos (Other)
结局指标
主要结局
Treatment success
时间窗: 2 months
Proportion of women with treatment success defined as normalization of serum hCG level \<10IU/L without additional medical or surgical intervention
次要结局
- Duration of hospitalization(2 months)
- hCG normalization duration(2 months)
- Number of participants experienced side effects(2 months)
- Participant satisfaction: proportion of women who would recommend this treatment to a friend(2 months)
研究者
Evelyn Wong
Associate consultant
Queen Mary Hospital, Hong Kong