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.