Study on Combined Use of Letrozole, Mifepristone and Misoprostol in Termination of Pregnancy
|ClinicalTrials.gov Identifier: NCT01475318|
Recruitment Status : Unknown
Verified November 2011 by The University of Hong Kong.
Recruitment status was: Recruiting
First Posted : November 21, 2011
Last Update Posted : November 21, 2011
|Condition or disease||Intervention/treatment|
|Complete Abortion||Drug: mifepristone Drug: Letrozole Drug: Misoprostol|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2011|
|Estimated Primary Completion Date :||June 2012|
|Estimated Study Completion Date :||June 2012|
|Experimental: misoprostol + mifepristone + letrozole||
200 mg mifepristone on day 1Drug: Letrozole
Letrozole 10mg PO on day 1, day 2, and day 3Drug: Misoprostol
misoprostol 800mcg PV on day 3
- Complete abortion rate [ Time Frame: from drug administration till return of next menses (average 4-6 weeks) ]If no suction evacuation is required before the return of next menstruation, it is classified as complete abortion
- the induction-to-abortion interval [ Time Frame: drug administration to passage of abortus (average within 48 hours) ]The time between administration of misoprostol and spontaneous passage of tissue mass
- incidence of side effects [ Time Frame: drug administration (D1) till D43 ]A list of side effects (nausea, vomiting, diarrhoea, fever, chills, headache, abdominal pain, bleeding) will be given to patient for record
- the duration of bleeding [ Time Frame: drug administration till cessation of bleeding (average 4-6 weeks) ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01475318
|Hong Kong, Hong Kong|
|Contact: Joyce Chai, MBChB 852-22555996 email@example.com|
|Principal Investigator: Joyce Chai, MBChB|
|Sub-Investigator: Pak Chung Ho, MD|