Study on Combined Use of Letrozole, Mifepristone and Misoprostol in Termination of Pregnancy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by The University of Hong Kong.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
The University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01475318
First received: October 31, 2011
Last updated: November 16, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention
Complete Abortion
Drug: mifepristone
Drug: Letrozole
Drug: Misoprostol

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • Complete abortion rate [ Time Frame: from drug administration till return of next menses (average 4-6 weeks) ] [ Designated as safety issue: No ]
    If no suction evacuation is required before the return of next menstruation, it is classified as complete abortion


Secondary Outcome Measures:
  • the induction-to-abortion interval [ Time Frame: drug administration to passage of abortus (average within 48 hours) ] [ Designated as safety issue: No ]
    The time between administration of misoprostol and spontaneous passage of tissue mass

  • incidence of side effects [ Time Frame: drug administration (D1) till D43 ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: October 2011
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: misoprostol + mifepristone + letrozole Drug: mifepristone
200 mg mifepristone on day 1
Drug: Letrozole
Letrozole 10mg PO on day 1, day 2, and day 3
Drug: Misoprostol
misoprostol 800mcg PV on day 3

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • good general health
  • older than the age of legal consent (i.e. >18 years old)
  • requesting medical abortion and eligible for abortion
  • on Day 1 of the study (day of letrozole and mifepristone administration) the duration of pregnancy not more than 63 days as confirmed by pelvic ultrasound examination
  • intrauterine pregnancy (intrauterine amniotic sac seen in US)
  • willing to use other than hormonal or intra-uterine contraception until the first menses after termination of pregnancy
  • if treatment should fail agrees to termination of pregnancy with the surgical method
  • willing and able to participate after the study has been explained
  • haemoglobin higher than 10g/L, normal liver and renal function

Exclusion Criteria:

  • a history or evidence of adrenal pathology, steroid-dependent cancer, porphyria, diastolic pressure over 95mm Hg, bronchial asthma, arterial hypotension
  • a history or evidence of thrombo-embolism, severe or recurrent liver disease or pruritus of pregnancy
  • the regular use of prescription drugs before admission to the study
  • the presence of an IUCD in utero
  • breast-feeding
  • multiple pregnancies
  • heavy smoker of more than 20 cigarettes per day
  • any abnormal values in pre-treatment blood tests
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01475318

Locations
Hong Kong
Joyce Chai Recruiting
Hong Kong, Hong Kong
Contact: Joyce Chai, MBChB    852-22555996    jchai@hkucc.hku.hk   
Principal Investigator: Joyce Chai, MBChB         
Sub-Investigator: Pak Chung Ho, MD         
Sponsors and Collaborators
The University of Hong Kong
  More Information

No publications provided

Responsible Party: The University of Hong Kong
ClinicalTrials.gov Identifier: NCT01475318     History of Changes
Other Study ID Numbers: mifemisolet
Study First Received: October 31, 2011
Last Updated: November 16, 2011
Health Authority: Hong Kong: Ethics Committee

Keywords provided by The University of Hong Kong:
complete abortion rate
side effects
induction-to-abortion interval

Additional relevant MeSH terms:
Mifepristone
Misoprostol
Letrozole
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Luteolytic Agents
Menstruation-Inducing Agents
Abortifacient Agents, Steroidal
Abortifacient Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Oxytocics
Abortifacient Agents, Nonsteroidal
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014