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

NCT05341817 | Recruiting Phase 4

• 1 other identifier: CIRB 202110-00035
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief 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. 1.Oral letrozole 10mg daily for 3 days, followed by vaginal misoprostol on Day 3 (Intervention group)
2. 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).

Conditions

Abortion in First Trimester

Keywords

Medical termination of pregnancy; Abortion; Induced; mTOP; letrozole; mifepristone; misoprostol

Outcome Measures

Primary Outcomes (1)

• Rate of complete abortion by Day 21-28

  Rate of complete abortion by Day 21-28 (defined as no further intervention required e.g. medical or surgical treatment for retained products of conception)

  Day 21-28 of study procedure

Secondary Outcomes (11)

• Number of patients who require surgical evacuation of uterus for retained product of conception (POC)

  Day 1-28 of study procedure

• Number of patients who require repeated medical therapy for retained product of conception (POC)

  Day 1-28 of study procedure, After Day 28 of study procedure

• Number of doses of misoprostol administered for expulsion of product of conception (POC)

  Day 3-4 of study procedure

• Time interval between administration of first dose of misoprostol and expulsion of product of conception (POC)

  Day 3-4 of study procedure

• Number of patients who need blood transfusion

  Day 1-28 of study procedure, After Day 28 of study procedure

Study Arms (2)

Letrozole

EXPERIMENTAL

Day 1: Oral letrozole 10mg under direct observation therapy (DOT) in the clinic Day 2: Oral letrozole 10mg to self-administer at home Day 3: Oral letrozole 10mg to self-administer at home or at the hospital. Vaginal misoprostol 800mcg given in the ward, followed by vaginal misoprostol 400mcg, approximately 4 hours later, if subject showed no signs of abortion

Drug: Letrozole

Control

ACTIVE COMPARATOR

Day 1: Oral mifepristone 200mg (control) under direct observation therapy (DOT) in clinic Day 2: NIL medication to be self-administered at home Day 3: NIL medication to be self-administered at home. Vaginal misoprostol 800mcg given in the ward, followed by vaginal misoprostol 400mcg, approximately 4 hours later, if subject showed no signs of abortion

Drug: Mifepristone

Interventions

Letrozole DRUG

Letrozole priming before mTOP is used as an alternative to the use of mifepristone. Women randomly assigned (1:1) to the Letrozole arm will receive 10 mg letrozole daily for 3 days followed by 800 μg misoprostol.

Letrozole

Mifepristone DRUG

Mifepristone priming before mTOP is the current standard of care. Women randomly assigned (1:1) to the Control arm will receive 200 mg mifepristone followed by 800 μg misoprostol 2 days later.

Control

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• KK Women's and Children's Hospital: lead

Study Sites (1)

KK Women&#39;s and Children&#39;s Hospital

Singapore, 229899, Singapore

RECRUITING

Related Publications (25)

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  PMID: 27179755 BACKGROUND

• Medical management of abortion. Geneva: World Health Organization; 2018. Available from http://www.ncbi.nlm.nih.gov/books/NBK536779/

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• Creinin MD, Shore E, Balasubramanian S, Harwood B. The true cost differential between mifepristone and misoprostol and misoprostol-alone regimens for medical abortion. Contraception. 2005 Jan;71(1):26-30. doi: 10.1016/j.contraception.2004.07.011.

  PMID: 15639068 BACKGROUND

• Shi L, Shi SQ, Given RL, von Hertzen H, Garfield RE. Synergistic effects of antiprogestins and iNOS or aromatase inhibitors on establishment and maintenance of pregnancy. Steroids. 2003 Nov;68(10-13):1077-84. doi: 10.1016/j.steroids.2003.09.002.

  PMID: 14668001 BACKGROUND

• Lee VC, Gao J, Lee KF, Ng EH, Yeung WS, Ho PC. The effect of letrozole with misoprostol for medical termination of pregnancy on the expression of steroid receptors in the placenta. Hum Reprod. 2013 Nov;28(11):2912-9. doi: 10.1093/humrep/det345. Epub 2013 Aug 26.

  PMID: 23980056 BACKGROUND

• Lee VC, Yeung TW, Tang OS, Ng EH, Yeung WS, Ho PC. Effect of letrozole on uterine artery Doppler flow indices prior to first-trimester termination of pregnancy: a randomized controlled trial. Ultrasound Obstet Gynecol. 2012 Oct;40(4):392-7. doi: 10.1002/uog.11115.

  PMID: 22302719 BACKGROUND

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• Lee VCY, Ng EHY, Yeung WSB, Ho PC. Misoprostol with or without letrozole pretreatment for termination of pregnancy: a randomized controlled trial. Obstet Gynecol. 2011 Feb;117(2 Pt 1):317-323. doi: 10.1097/AOG.0b013e3182073fbf.

  PMID: 21252745 BACKGROUND

• Nash CM, Philp L, Shah P, Murphy KE. Letrozole pretreatment prior to medical termination of pregnancy: a systematic review. Contraception. 2018 Jun;97(6):504-509. doi: 10.1016/j.contraception.2017.11.003. Epub 2017 Nov 14.

  PMID: 29154779 BACKGROUND

• Zhuo Y, Cainuo S, Chen Y, Sun B. The efficacy of letrozole supplementation for medical abortion: a meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med. 2021 May;34(9):1501-1507. doi: 10.1080/14767058.2019.1638899. Epub 2019 Jul 29.

  PMID: 31257957 BACKGROUND

• Behroozi-Lak T, Derakhshan-Aydenloo S, Broomand F. Evaluation of effect of letrozole prior to misoprostol in comparison with misoprostol alone in success rate of induced abortion. J Gynecol Obstet Hum Reprod. 2018 Mar;47(3):113-117. doi: 10.1016/j.jogoh.2017.11.002. Epub 2017 Nov 6.

  PMID: 29122709 BACKGROUND

• Naghshineh E, Allame Z, Farhat F. The effectiveness of using misoprostol with and without letrozole for successful medical abortion: A randomized placebo-controlled clinical trial. J Res Med Sci. 2015 Jun;20(6):585-9. doi: 10.4103/1735-1995.165964.

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• Rezai Z, Heydari Bazardehi S S, Ghasemi Nezhad A, Sadeghi A S, Ghorbani Yekta B. (2014). Letrozole and misoprostol versus misoprostol alone for termination of pregnancy: a randomized clinical trial. Tehran Univ Med J, 71 (11), 700-706

  BACKGROUND

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  PMID: 12042265 BACKGROUND

• Blum J, Raghavan S, Dabash R, Ngoc Nt, Chelli H, Hajri S, Conkling K, Winikoff B. Comparison of misoprostol-only and combined mifepristone-misoprostol regimens for home-based early medical abortion in Tunisia and Vietnam. Int J Gynaecol Obstet. 2012 Aug;118(2):166-71. doi: 10.1016/j.ijgo.2012.03.039. Epub 2012 Jun 8.

  PMID: 22682768 BACKGROUND

• Dahiya K, Ahuja K, Dhingra A, Duhan N, Nanda S. Efficacy and safety of mifepristone and buccal misoprostol versus buccal misoprostol alone for medical abortion. Arch Gynecol Obstet. 2012 Apr;285(4):1055-8. doi: 10.1007/s00404-011-2110-8. Epub 2011 Oct 19.

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• Ngoc NT, Blum J, Raghavan S, Nga NT, Dabash R, Diop A, Winikoff B. Comparing two early medical abortion regimens: mifepristone+misoprostol vs. misoprostol alone. Contraception. 2011 May;83(5):410-7. doi: 10.1016/j.contraception.2010.09.002. Epub 2010 Oct 18.

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• Allen R, O'Brien BM. Uses of misoprostol in obstetrics and gynecology. Rev Obstet Gynecol. 2009 Summer;2(3):159-68.

  PMID: 19826573 BACKGROUND

• Chai J, Ho PC. A pilot study on the combined use of letrozole, mifepristone and misoprostol in termination of first trimester pregnancy up to 9 weeks' gestation. Eur J Obstet Gynecol Reprod Biol. 2013 Dec;171(2):291-4. doi: 10.1016/j.ejogrb.2013.09.017. Epub 2013 Sep 25.

  PMID: 24135383 BACKGROUND

• Yeung TW, Lee VC, Ng EH, Ho PC. A pilot study on the use of a 7-day course of letrozole followed by misoprostol for the termination of early pregnancy up to 63 days. Contraception. 2012 Dec;86(6):763-9. doi: 10.1016/j.contraception.2012.05.009. Epub 2012 Jun 18.

  PMID: 22717187 BACKGROUND

• (Power Analysis and Sample Size Software (2015). NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass.)

  BACKGROUND

• Lee VC, Tang OS, Ng EH, Yeung WS, Ho PC. A pilot study on the use of letrozole with either misoprostol or mifepristone for termination of pregnancy up to 63 days. Contraception. 2011 Jan;83(1):62-7. doi: 10.1016/j.contraception.2010.05.014. Epub 2010 Jun 23.

  PMID: 21134505 BACKGROUND

MeSH Terms

Interventions

Letrozole; Mifepristone

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Meei Jiun Seet

  Consultant at KK Women&amp;#39;s and Children&amp;#39;s Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meei Jiun Seet

CONTACT

(+65) 97865163; julin.wong.sx@kkh.com.sg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Masking Details: The treatment doctor during the Day 21-28 follow-up visit will be blinded to the treatment allocation of the study participant.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 22, 2022
• Study Start: November 22, 2022
• Primary Completion: August 1, 2025
• Study Completion: November 1, 2025
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)