The Use of Letrozole or Mifepristone for Pretreatment of Medical Termination of Pregnancy

• Status: Not yet recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: Female

Summary

Medical termination of pregnancy (mTOP) generally involves using either a combined regimen consisting of mifepristone and misoprostol, or a misoprostol-only regimen. Complete abortion rates of first trimester mTOP with the use of misoprostol-only regimen varies between 74-88%. With the addition of mifepristone as pre-treatment drug, this improves success rates to 93-97%. Mifepristone, an anti-progesterone, is relatively expensive and is subject to stringent regulations for usage in addition to restricted access in many countries. Therefore, there is a need to find a cheaper and more readily available, yet effective alternative.

The use of letrozole (an aromatase inhibitor) in mTOP is postulated to suppress estradiol levels (an important factor in the maintenance of early pregnancy), therefore enhancing the effect of misoprostol in inducing abortion. Studies have shown that pre-treatment with letrozole achieves a complete abortion rate of 77-98%, similar to that in mifepristone-Misoprostol studies.

The investigators hypothesise that letrozole is equivalent to mifepristone for the pre-treatment of mTOP and propose to conduct a randomised, non-inferiority trial for mTOP up to 10 weeks gestation with two arms as detailed below:

1. Oral letrozole 10mg daily for 3 days, followed by vaginal misoprostol on Day 3 (Intervention group)

2. Oral mifepristone 200mg once on Day 1, followed by vaginal misoprostol 800mcg on Day 3. Then, 4 hours later, another dose of 400mcg PV misoprostol if no signs of abortion (Control group - current practice).

The investigators aim to include a total of 144 patients, 72 in each arm, to detect a non-inferiority margin of 15% with a power of 80% at 5% significance. The investigators primary outcome will be rate of complete abortion by Day 21-28 of mTOP.

This pilot RCT will provide preliminary data and preparation for larger grant application which will provide necessary evidence to enhance the care of women undergoing mTOP, with enhanced cost-savings and availability.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: KK Women's and Children's Hospital
• Treatments: Letrozole; Mifepristone

Criteria

Inclusion Criteria:

• 21 years and above

• Patient requesting for medical termination of pregnancy (mTOP)

• Patient eligible for legal abortion according to the Termination of Pregnancy Act (Chapter 324)

• Gestational age ≤10 weeks (on day 1 of mifepristone or letrozole administration) as confirmed by the first trimester dating scan

• Singleton pregnancy

• Patient is agreeable to undergo surgical evacuation or repeat medical therapy if treatment fails

• Willing and able to provide written, informed consent

Exclusion Criteria:

• History or evidence of adrenal pathology, steroid-dependent cancer, porphyria, poorly controlled hypertension, bronchial asthma, thromboembolism and severe cardiac/renal/liver disease

• Haemoglobin level of <9.5 g/L

• Presence of an intrauterine contraceptive device

• Breastfeeding

• Reported allergic reaction to mifepristone, misoprostol or letrozole,

• Participating in another trial of investigational medicinal products during the current pregnancy