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.
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.
Singapore1 site, 1 recruiting
- Recruiting
KK Women's and Children's Hospital
Singapore, 229899
Meei Jiun Seet, julin.wong.sx@kkh.com.sg
Julin Shuxian Wong, julin.wong.sx@kkh.com.sg
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:
- Oral letrozole 10mg daily for 3 days, followed by vaginal misoprostol on Day 3 (Intervention group)
- 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.
- Conditions
- Abortion in First Trimester
- 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 group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Mifepristone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Number of patients who require surgical evacuation of uterus for retained product of conception (POC)
Measured: Day 1-28 of study procedure
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
Number of doses of misoprostol administered for expulsion of product of conception (POC)
Measured: Day 3-4 of study procedure
Time interval between administration of first dose of misoprostol and expulsion of product of conception (POC)
Measured: Day 3-4 of study procedure
Number of patients who need blood transfusion
Measured: Day 1-28 of study procedure, After Day 28 of study procedure
Number of patients who require analgesia according to the analgesic ladder
Measured: Day 1-4 of study procedure
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
Length of hospital stay
Measured: Day 1-28 of study procedure, After Day 28 of study procedure
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
Number of patients who develop severe allergic reactions
Measured: Day 1-28 of study procedure, After Day 28 of study procedure
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.
- First posted22 Apr 2022
- Study start22 Nov 2022
- Primary completionAug 2025 (estimated)
- Study completionNov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Abortion in First TrimesterStudies of the same condition, open and under way.
- More trials run by KK Women's and Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- KK Women's and Children's Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Seet Meei Jiun, KK Women's and Children's Hospital
- Investigators
- Meei Jiun Seet, Principal investigator, Consultant at KK Women&#39;s and Children&#39;s Hospital, Singapore
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 27179755Medical management of abortion. Geneva: World Health Organization; 2018. Available from http://www.ncbi.nlm.nih.gov/books/NBK536779/
PubMed 30702834Abubeker 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 32635921Creinin 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 15639068Shi 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 14668001Lee 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 23980056Lee 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 22302719Yung 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 26707996Lee 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 21252745Nash 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 29154779Zhuo 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 31257957Behroozi-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 29122709Naghshineh 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 26600834Rezai 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
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Letrozole or Mifepristone for Pretreatment of Medical Termination of Pregnancy: a Randomized, Non-inferiority Trial
- ClinicalTrials.gov ID
- NCT05341817
- Acronym / sponsor ID
- CIRB 202110-00035
- Conditions
- Abortion in First Trimester
- Keywords
- Medical termination of pregnancy, Abortion, Induced, mTOP, letrozole, mifepristone, misoprostol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- KK Women's and Children's HospitalOther government
- Study start
- 22 Nov 2022 (actual)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Nov 2025 (estimated)
- First posted
- 22 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Oral letrozole 10mg daily for 3 days, followed by vaginal misoprostol on Day 3 (Intervention group)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letrozole | Experimental | Drug: LetrozoleDay 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 |
| Control | Active comparator | Drug: MifepristoneDay 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 |
Who may qualify
- Ages
- 21 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LetrozoleLetrozole 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. | Drug | Letrozole |
| MifepristoneMifepristone 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. | Drug | Control |
Primary outcome
Rate of complete abortion by Day 21-28
Time frame: Day 21-28 of study procedure
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)
11 secondary outcomes
Number of patients who require surgical evacuation of uterus for retained product of conception (POC)
Time frame: Day 1-28 of study procedure
Number of patients who require repeated medical therapy for retained product of conception (POC)
Time frame: 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)
Time frame: Day 3-4 of study procedure
Time interval between administration of first dose of misoprostol and expulsion of product of conception (POC)
Time frame: Day 3-4 of study procedure
Number of patients who need blood transfusion
Time frame: Day 1-28 of study procedure, After Day 28 of study procedure
Number of patients who require analgesia according to the analgesic ladder
Time frame: Day 1-4 of study procedure
Number of patients who experience minor side effects including pain, bleeding, fever, vomiting and diarrhoea
Time frame: Day 1-28 of study procedure, After Day 28 of study procedure
Length of hospital stay
Time frame: Day 1-28 of study procedure, After Day 28 of study procedure
Number of patients who require unscheduled emergency department visit or hospital admission
Time frame: Day 1-28 of study procedure, After Day 28 of study procedure
Number of patients who develop severe allergic reactions
Time frame: Day 1-28 of study procedure, After Day 28 of study procedure
Number of adverse events reported
Time frame: Day 1-28 of study procedure, After Day 28 of study procedure
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2025.
- Background: PubMed 27179755Sedgh 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.
- Background: PubMed 30702834Medical management of abortion. Geneva: World Health Organization; 2018. Available from http://www.ncbi.nlm.nih.gov/books/NBK536779/
- Background: PubMed 32635921Abubeker 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.
- Background: PubMed 15639068Creinin 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.
- Background: PubMed 14668001Shi 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.
- Background: PubMed 23980056Lee 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.
- Background: PubMed 22302719Lee 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.
- Background: PubMed 26707996Yung 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.
- Background: PubMed 21252745Lee 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.
- Background: PubMed 29154779Nash 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.
- Background: PubMed 31257957Zhuo 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.
- Background: PubMed 29122709Behroozi-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Meei Jiun Seet principal investigator
Consultant at KK Women&#39;s and Children&#39;s Hospital, Singapore
1 site in 1 country: see every site and its status.
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.