Complete Abortion Clinical Trial
Official title:
A Pilot Study on the Combined Use of Letrozole, Miferpristone and Misoprostol in Termination of First Trimester Pregnancy up to 63 Days Gestation
By using the combination of mifepristone (anti-progestin), misoprostol (progstanglandin which stimulates uterine contraction), and letrozole (aromatise inhibitor which reduces estrogen production), the abortion process will be more effective.
After mifepristone was approved by the United States Food and Drug Administration in 2000,
the combination of mifepristone 200 mg and vaginal use of misoprostol 800 mcg became almost
a standard of care in early medical abortion up to 63 days of gestation. Misoprostol, a
synthetic analogue of naturally occurring prostaglandin E1, has uterotonic effect and it can
stimulate myometrial contraction and cause cervical ripening and dilatation. Progesterone
maintains the uterus in a quiescent state by inducing hyperpolarization of the membrane of
the myometrial cells and a greater change in electric potential is necessary before
contractions can occur. Mifepristone is the anti-progestin that binds to the progesterone
receptors and prevents endogenous progesterone from exerting is effects. It can also
increase the sensitivity of the uterus to prostaglandins. The complete abortion rate
achieved with this sequential regimen has been found to be up to 93-95%, which is higher
than the rate achieved with either mifepristone or misoprostol alone.
Apart from progesterone, estrogen is another important hormone for the maintenance of
pregnancy. Albrecht et al showed that 50% of the baboons miscarried when maternal estrogen
synthesis was suppressed using aromatase inhibitors whereas all maintained their pregnancy
when concomitant estradiol was given. Letrozole is a third-generation aromatase inhibitor
which leads to reduced production of estrogen and has specific actions at clinical doses
with no effect on basal levels of cortisol and aldosterone. Shi et al found that the
combinations of anti-progestin with aromatase inhibitor act synergistically to induce 100%
abortion rate in rats, with little effect of antiprogestin or aromatase inhibitor when
administered alone. Lee et al conducted the first pilot study of the effect of letrozole on
medical abortions of up to 9 weeks gestation in humans. When 7.5 mg letrozole was combined
with 200 mg mifepristone, the abortion effect was not as great as those observed in animal
study, with clinical complete abortion rate of 71% only. On the other hand, when 7.5 mg
letrozole was given daily for 2 days followed by 800 mcg vaginal misoprostol, this regimen
was associated with a clinical complete abortion rate of 80% and 87.5% with gestation of
less than 63 days and gestation of less than 49 days respectively. Hormonal profiles
revealed that letrozole led to significant reduction in oestradiol level, but progesterone
level was not altered. The complete abortion rate achieved was noted to be higher when the
dosage and duration of letrozole were increased to 10 mg for 3 days. There were no serious
complications encountered in these 200 subjects, implying that these regimens are likely
safe to use in humans.
Letrozole plays a role in medical termination through its principal effect on oestrodial
synthesis, which is an important factor in the maintenance of early pregnancy. It is
postulated that by combining both letrozole and mifepristone, together with misoprostol, a
synergistic effect will be exerted as the depleted estrogen and progesterone level will be
insufficient to support the pregnancy, and the uterotonic effect of misoprostol will hasten
the abortion process, hence improving the complete abortion rate. The aim of this pilot
study was to determine the complete abortion rate of vaginal misoprostol when given with
mifepristone and letrozole for termination of first trimester pregnancy up to 9 weeks
gestation.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02018796 -
Mifepristone and Misoprostol for the Termination of Pregnancy up to 70 Days' Gestation in Kazakhstan
|
N/A | |
| Completed |
NCT01387256 -
Comparing Two Regimens for Medical Abortion: Mifepristone + Misoprostol Versus Misoprostol Alone
|
Phase 4 |