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Abortion in First TrimesterPhase 4NCT05341817

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

A Phase 4 study testing Letrozole and Mifepristone in people with Abortion in First Trimester, run by KK Women's and Children's Hospital at 1 site in Singapore.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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%. Read more about this study

Who is it for?
Ages 21 years and older, women only
Conditions the study is for
Abortion in First Trimester
What is being tested?
Letrozole and Mifepristone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
144 participants
Where
1 siteSingapore
Study dates
22 Nov 2022to Nov 2025
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Meei Jiun Seet contact

(+65) 97865163

julin.wong.sx@kkh.com.sg

Singapore1 site, 1 recruiting

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

    Singapore, 229899

    Meei Jiun Seet, julin.wong.sx@kkh.com.sg

    Julin Shuxian Wong, julin.wong.sx@kkh.com.sg

    Recruiting

Other trials in Singapore

About this study

Official title: The Use of Letrozole or Mifepristone for Pretreatment of Medical Termination of Pregnancy: a Randomized, Non-inferiority Trial

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.

Read more

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.

Read the detailed description

The standard of care for termination of pregnancy (TOP) has shifted from a predominantly surgical approach towards medical strategy. Medical termination of pregnancy (mTOP) has increased in popularity worldwide as it is cost savings, non-invasive and there is avoidance of risks associated with surgery.

In general, mTOP involves using either a combined regimen consisting of mifepristone and misoprostol which is the current gold standard of care, or a misoprostol-only regimen. The World Health Organisation (WHO) recommends the use of mifepristone for pre-misoprostol priming when mifepristone is available, and the alternative of misoprostol-only when mifepristone is not accessible. Compared with misoprostol alone, pre-treatment with mifepristone followed by misoprostol has been shown to improve the success rate of complete abortion. However, the widespread use of mifepristone is limited by the high cost of therapy and unavailability in many countries. Hence, there is an urgent unmet need for a cheaper and more readily available alternative.

Letrozole priming before mTOP has been proposed as an alternative to the use of mifepristone. The proposed mechanism is a reduction in serum estrogen levels, leading to a concomitant reduction in progesterone receptor concentration necessary for the maintenance of pregnancy. Several randomised controlled trials (RCTs) have been performed by comparing the effectiveness of using letrozole for mTOP priming before misoprostol versus misoprostol alone. The combination of letrozole with misoprostol has shown to be effective in improving the success rates of complete abortion up to 10 weeks gestation, compared with misoprostol alone. Given its low price, ready availability worldwide and common usage in the fields of ovulation induction and breast cancer, letrozole may be a potential alternative to mifepristone in mTOP priming. While medication costs vary from country to country, the cost of a course of letrozole is largely cheaper than mifepristone. Unfortunately, no study has been designed to specifically compare the effectiveness of letrozole versus mifepristone pre-treatment regimes in the management of mTOP. Independent examination of the pre-treatment effects of letrozole and misoprostol versus misoprostol alone in different studies (different population characteristics) restricted valid comparison between treatments. This forms the key motivation for the investigators' proposed study.

To address the aforementioned knowledge gaps, this study aims to conduct a non-inferior RCT to investigate whether pre-treatment with letrozole before misoprostol is comparable to mifepristone pre-treatment before misoprostol mTOP in patients up to 10 weeks gestation. Women will be randomly assigned (1:1) to either receive 10 mg letrozole daily for 3 days followed by 800 μg misoprostol, or 200 mg mifepristone followed by 800 μg misoprostol 2 days later. This RCT is designed as a non-inferiority trial. Thus, the investigators expect that no significant differences in abortion outcomes will be observed between the two groups.

The primary outcome is complete abortion rates. Secondary outcomes include time-to-abortion interval, the number of misoprostol doses required, healthcare resource utilisation and side effects.

Specific Aim 1: To compare complete abortion rates at day 21-28 of mTOP in patients using letrozole/misoprostol regime versus mifepristone/misoprostol regime. The investigators hypothesise that letrozole will achieve similar complete abortion rates as mifepristone when used as priming of mTOP. Complete abortion will be defined as no further intervention required e.g. medical or surgical treatment for retained products of conception.

Specific Aim 2: To determine if letrozole/misoprostol regime results in better healthcare resource utilisation than mifepristone/misoprostol regime. The investigators hypothesise that letrozole is a resource-efficient alternative as measured by length of hospital stay, need for emergency department attendance and need for additional medical/surgical treatment.

The successful completion of this RCT will provide the data necessary to show the non-inferiority of letrozole compared against mifepristone. This will lead to the introduction of a more cost-effective and more accessible mTOP service for patients, as letrozole is cheaper and more widely available as compared to mifepristone. The expansion of mTOP regimes may help to save hospital resources with less reliance on surgical methods (manpower and expertise, logistics, and cost etc.) in the long run.

Being tested
Letrozole, Mifepristone
Keywords
Medical termination of pregnancy, Abortion, Induced, mTOP, letrozole, mifepristone, misoprostol

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LetrozoleDrug

    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.

  • MifepristoneDrug

    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.

Study groups in NCT05341817
Study groupRoleWhat they receive
LetrozoleExperimentalDay 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
Receives: Drug: Letrozole
ControlActive comparatorDay 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
Receives: Drug: Mifepristone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: Day 21-28 of study procedure

Secondary outcomes (11)

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

    Measured: Day 1-28 of study procedure

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

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

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

    Measured: Day 3-4 of study procedure

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

    Measured: Day 3-4 of study procedure

  5. Number of patients who need blood transfusion

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

  6. Number of patients who require analgesia according to the analgesic ladder

    Measured: Day 1-4 of study procedure

  7. Number of patients who experience minor side effects including pain, bleeding, fever, vomiting and diarrhoea

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

  8. Length of hospital stay

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

  9. Number of patients who require unscheduled emergency department visit or hospital admission

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

  10. Number of patients who develop severe allergic reactions

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

  11. Number of adverse events reported

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Apr 2022
  2. Study start22 Nov 2022
  3. Primary completionAug 2025 (estimated)
  4. Study completionNov 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Care provider
Enrolment
144 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05341817
Sponsor's protocol ID
CIRB 202110-00035
Status last verified
Jan 2025
First submitted
5 Apr 2022
Last updated
22 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Sedgh G, Bearak J, Singh S, Bankole A, Popinchalk A, Ganatra B, Rossier C, Gerdts C, Tuncalp O, Johnson BR Jr, Johnston HB, Alkema L. Abortion incidence between 1990 and 2014: global, regional, and subregional levels and trends. Lancet. 2016 Jul 16;388(10041):258-67. doi: 10.1016/S0140-6736(16)30380-4. Epub 2016 May 11.

    PubMed 27179755

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

    PubMed 30702834

  • Abubeker FA, Lavelanet A, Rodriguez MI, Kim C. Medical termination for pregnancy in early first trimester (</= 63 days) using combination of mifepristone and misoprostol or misoprostol alone: a systematic review. BMC Womens Health. 2020 Jul 7;20(1):142. doi: 10.1186/s12905-020-01003-8.

    PubMed 32635921

  • 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.

    PubMed 15639068

  • 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.

    PubMed 14668001

  • 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.

    PubMed 23980056

  • 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.

    PubMed 22302719

  • Yung SSF, Lee VCY, Chiu PCN, Li HWR, Ng EHY, Yeung WSB, Ho PC. The effect of 7 days of letrozole pretreatment combined with misoprostol on the expression of progesterone receptor and apoptotic factors of placental and decidual tissues from first-trimester abortion: a randomized controlled trial. Contraception. 2016 Apr;93(4):323-330. doi: 10.1016/j.contraception.2015.12.005. Epub 2015 Dec 19.

    PubMed 26707996

  • 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.

    PubMed 21252745

  • 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.

    PubMed 29154779

  • 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.

    PubMed 31257957

  • 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.

    PubMed 29122709

  • 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.

    PubMed 26600834

  • 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

  • Chawdhary R, Rana A, Pradhan N. Mifepristone plus vaginal misoprostol vs vaginal misoprostol alone for medical abortion in gestation 63 days or less in Nepalese women: a quasi-randomized controlled trial. J Obstet Gynaecol Res. 2009 Feb;35(1):78-85. doi: 10.1111/j.1447-0756.2008.00864.x.

    PubMed 19215552

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Letrozole and Mifepristone in people with Abortion in First Trimester, run by KK Women's and Children's Hospital at 1 site in Singapore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Meei Jiun Seet ((+65) 97865163, julin.wong.sx@kkh.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of complete abortion by Day 21-28 (time frame: Day 21-28 of study procedure). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05341817, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2025.

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