Letrozole Versus Mifepristone and Misoprostol in Silent Miscarriage

Not Applicable

Not yet recruiting

• Conditions: Silent Miscarriage
• Interventions: Drug: Letrozole; Drug: Mifepristone

• Registration Number: NCT06733727
• Lead Sponsor: The University of Hong Kong

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.

Study Timeline

• Status Verified: 2024-08
• Study Start: 2024-12-06
• Study First Submitted: 2024-12-06
• Study First Submitted QC: 2024-12-09
• Last Update Submitted: 2024-12-09
• Study First Posted: 2024-12-13
• Last Update Posted: 2024-12-13
• Primary Completion: 2027-12-05
• Study Completion: 2028-06-05

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 884

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Letrozole	Letrozole	Letrozole 10mg per day from day 1-3 orally, placebo mifepristone Sublingual misoprostol 800 microgram on day 3
Mifepristone	Mifepristone	Mifepristone 200mg orally on day 1, placebo letrozole on day 1-3 Sublingual misoprostol 800 microgram on day 3

Primary Outcome Measures

Name	Time	Method
Gestational sac expulsion	2 weeks, 30 days	Gestational sac expulsion by the first follow up visit after 2 weeks of misoprostol administration and no additional surgical or medical intervention within 30 days after randomization

Secondary Outcome Measures

Name	Time	Method
Time of tissue expulsion	6 weeks	Time of tissue expulsion
Return of normal menses	6 weeks	Return of normal menses without additional intervention
Requirement of repeated intervention	6 weeks	Requirement of repeated intervention including repeated course of medical treatment or surgery
Unplanned re-admission	6 weeks	Number of unplanned re-admission
Analgesics	6 weeks	Use of analgesics
Side effects	6 weeks	Abdominal pain on a visual analog scale
Vaginal bleeding	6 weeks	Duration and amount of vaginal bleeding
Complications	6 weeks	Including severe vaginal bleeding requiring transfusion, infection
Return of menstruation	6 weeks	Timing of return of menses
Women's satisfaction	6 weeks	EQ-5D-5L questionnaire