Clinical trial NCT06733727: Letrozole Versus Mifepristone and Misoprostol in Silent Miscarriage
Official title: A Randomized Double-blind Placebo-controlled Trial Comparing Letrozole Versus Mifepristone As Pre-treatment Before Medical Management of First Trimester Silent Miscarriage Using Misoprostol
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Silent Miscarriage
Keywords: silent miscarriage
mifepristone
misoprostol
letrozole
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Queen Mary Hospital, Hong Kong
name: Pamela Youde Nethersole Eastern Hospital
name: Kwong Wah Hospital
name: Princess Margaret Hospital, Canada
First posted: 2024-12-13
Enrollment: 884
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Management of first trimester silent miscarriage can be by expectant, medical or surgical management. Surgical management by suction evacuation is associated with surgical risks (including risks to the womb that can affect further pregnancy), anaesthetic risks and hospital stay. Medical management of first trimester silent miscarriage using misoprostol is another common option that can reduce the risk of bleeding and those associated with surgery. However, the current standard management of using misoprostol for the management of first trimester miscarriage only has a success rate of 70-80%, which is suboptimal.

Recent large studies have shown that adding mifepristone pre-treatment before misoprostol in the management of silent miscarriage can improve the success rates of complete miscarriage after medical management. There are 2 problems with mifepristone. Firstly, it is not widely available in many countries for cultural and religious reasons because it is labelled as an 'abortifacient'. Secondly, it is expensive. One tablet of Mifepristone costs $500 HK dollars. There is a need to look for an alternative to mifepristone.

Letrozole is an aromatase inhibitor which can reduce estrogen levels. Some studies have shown that it can improve the success rate of medical management of silent miscarriage and termination of pregnancy. It is safe, more widely available and cheaper than mifepristone.

This is a randomized double blinded trial comparing the use of mifepristone versus letrozole as pre-treatment in the medical management of first trimester silent miscarriage using misoprostol.

Detailed description: This is a randomized double blinded trial comparing the use of mifepristone versus letrozole as pre-treatment in the medical management of first trimester silent miscarriage using misoprostol.

Both groups will receive misoprostol (which is the standard management for medical management of silent miscarriage locally), but they will be randomized to either adding mifepristone or letrozole as pre-treatment. Mifepristone is usually taken once 2 days before misoprostol, whereas letrozole is taken 10mg daily for 3 days before misoprostol. Placebo of letrozole and mifepristone will be given to maintain double blindness of the groups.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with silent miscarriage \<= 12 weeks of gestation by ultrasonography
* Single intrauterine gestational sac
* No heavy per-vaginal bleeding
* No severe abdominal pain
* No features of intrauterine infection
* Able to understand the proposed research and able to comply with instructions
* Having given voluntary written informed consent

Exclusion Criteria:

* Known allergy to mifepristone, misoprostol or letrozole
* On drugs with potential drug interactions with mifepristone e.g. aspirin, clopidogrel, anti-coagulants etc.
* Suspected ectopic or molar pregnancy or multiple pregnancy
* Distorted uterine cavity by uterine septum or submucosal fibroids
* Presence of intrauterine contraceptive device
* History of bleeding tendencies e.g. haemorrhagic diseases, current anti-coagulant treatment
* Previous history of retained products of gestation/ failed medical management of miscarriage
* Opt for expectant or surgical management of miscarriage

Primary outcomes:
measure: Gestational sac expulsion
timeFrame: 2 weeks, 30 days
Secondary outcomes:
measure: Time of tissue expulsion
timeFrame: 6 weeks
measure: Return of normal menses
timeFrame: 6 weeks
measure: Requirement of repeated intervention
timeFrame: 6 weeks
measure: Unplanned re-admission
timeFrame: 6 weeks
measure: Analgesics
timeFrame: 6 weeks
measure: Side effects
timeFrame: 6 weeks
measure: Side effects
timeFrame: 6 weeks
measure: Side effects
timeFrame: 6 weeks
measure: Side effects
timeFrame: 6 weeks
measure: Side effects
timeFrame: 6 weeks
measure: Vaginal bleeding
timeFrame: 6 weeks
measure: Complications
timeFrame: 6 weeks
measure: Return of menstruation
timeFrame: 6 weeks
measure: Women's satisfaction
timeFrame: 6 weeks
measure: Women's satisfaction
timeFrame: 6 weeks
Other outcomes:
Locations:
Study officials:
affiliation: The University of Hong Kong
name: Jennifer Ko
role: PRINCIPAL_INVESTIGATOR
References: