MiMi: A Randomized Trial of Mifepristone and Misoprostol for Treatment of Early Pregnancy Failure

Miscarriage Clinical Trial

— MiMi  

Official title:

Treatment of Early Pregnancy Failure

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00468299
• Other study ID #: H-25999
• Status: Terminated
• Phase: N/A
• First received: May 1, 2007
• Last updated: June 23, 2011
• Start date: April 2007
• Est. completion date: December 2008

Study information

• Verified date: June 2011
• Source: Boston University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare two combinations of drugs (mifepristone and misoprostol versus placebo and misoprostol) used for medical treatment for early pregnancy failure. We will compare the two combinations of medications to see which combination makes miscarriage happen faster. We hypothesize that there will be no difference in time to complete miscarriage between the two groups.

Description:

The optimal method of treating Early Pregnancy Failure (EPF) is not certain. For many years, surgical management of EPF was the only treatment option. Now there are multiple studies demonstrating the effectiveness of misoprostol for treating EPF. Most of the studies investigating medical treatment of EPF have evaluated efficacy at one week. We have found that many women do not want to wait for one week for an outcome of their medical treatment, and want resolution sooner. This has hampered the widespread utilization of medical therapy in our institution.

We propose a regimen of medical treatment for EPF with expeditious follow-up. We want to demonstrate the relative efficacy of two medication regimens for treatment of EPF by performing a randomized trial. One regimen will be 800μg buccal misoprostol alone and the other regimen will be 200mg mifepristone, orally, in addition to 800μg buccal misoprostol, simultaneously. The primary outcome will be complete abortion rates 24hours after medication administration. We hypothesize that mifepristone will not improve complete abortion rates at 24hrs.

Secondary outcomes include rates of abortion by medical treatment at one week, the indications for surgical intervention, relationship of progesterone levels and type of pregnancy failure to outcomes in the two groups. Another secondary objective is to assess satisfaction with the treatment process at the conclusion of pregnancy termination, and 3 weeks after the beginning of the process.

The majority of studies investigating medical treatment of EPF use vaginal misoprostol, but buccal use is increasing. We will use buccal misoprostol, which is widely used at our institution. We will assess the efficacy of this route of administration as well as assess patient acceptability of this method.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Age >18yrs, able to read and write English

• Intrauterine gestations with anembryonic sac between 10 and 45mm or

• 10-15mm sac with no growth in three days or other radiologic signs of abnormal pregnancy such as irregular sac or debris within the gestational sac

• An embryonic pole <30mm with no cardiac activity

Exclusion Criteria:

• Intrauterine gestations with CRL <5mm or >30mm without cardiac activity

• Incomplete abortion as defined as open cervix and large amount of cramping/bleeding

• Hemodynamic instability and/or heavy vaginal bleeding

• Hemoglobin less than or equal to 8

• Inability to follow-up (ie, lack of transportation or access to telephone)

• Bleeding disorder or taking anticoagulants

• Prior medical or surgical treatment of the current pregnancy

• Obvious Infection

• Active Lactation

• Allergy to mifepristone or misoprostol

• Chronic corticosteroid use

• Severe gastrointestinal disease (e.g inflammatory bowel disease, severe gastritis)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abortion, Spontaneous
• Anembryonic Pregnancy
• Early Pregnancy Failure
• Fetal Death
• Fetal Demise
• Miscarriage

Intervention

Drug:
• Misoprostol and placebo
Women in this group receive 800 mcg misoprostol plus a placebo
• Mifepristone and misoprostol
This group receives mifepristone 200 mg orally; followed by 800 mcg misoprostol bucally

Locations

Country	Name	City	State
United States	Boston University	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boston University

Country where clinical trial is conducted

United States, 

References & Publications (15)

Bagratee JS, Khullar V, Regan L, Moodley J, Kagoro H. A randomized controlled trial comparing medical and expectant management of first trimester miscarriage. Hum Reprod. 2004 Feb;19(2):266-71. — View Citation

Creinin MD, Schwartz JL, Guido RS, Pymar HC. Early pregnancy failure--current management concepts. Obstet Gynecol Surv. 2001 Feb;56(2):105-13. Review. — View Citation

Lelaidier C, Saint-Mleux CB, Fernandez H, Bourget P, Frydman R. [Embryo expulsion induction in first trimester miscarriages. Use of mifepristone (RU 486) in a double blind prospective randomized study]. Contracept Fertil Sex. 1993 Jun;21(6):505-8. French. — View Citation

Lister MS, Shaffer LE, Bell JG, Lutter KQ, Moorma KH. Randomized, double-blind, placebo-controlled trial of vaginal misoprostol for management of early pregnancy failures. Am J Obstet Gynecol. 2005 Oct;193(4):1338-43. — View Citation

Meckstroth KR, Whitaker AK, Bertisch S, Goldberg AB, Darney PD. Misoprostol administered by epithelial routes: Drug absorption and uterine response. Obstet Gynecol. 2006 Sep;108(3 Pt 1):582-90. — View Citation

Middleton T, Schaff E, Fielding SL, Scahill M, Shannon C, Westheimer E, Wilkinson T, Winikoff B. Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period. Contraception. 2005 Nov;72(5):328-32. Epub 2005 Aug 9. — View Citation

Nielsen S, Hahlin M, Platz-Christensen JJ. Unsuccessful treatment of missed abortion with a combination of an antiprogesterone and a prostaglandin E1 analogue. Br J Obstet Gynaecol. 1997 Sep;104(9):1094-6. — View Citation

Schaff EA, DiCenzo R, Fielding SL. Comparison of misoprostol plasma concentrations following buccal and sublingual administration. Contraception. 2005 Jan;71(1):22-5. — View Citation

Stockheim D, Machtinger R, Wiser A, Dulitzky M, Soriano D, Goldenberg M, Schiff E, Seidman DS. A randomized prospective study of misoprostol or mifepristone followed by misoprostol when needed for the treatment of women with early pregnancy failure. Fertil Steril. 2006 Oct;86(4):956-60. — View Citation

Tang OS, Schweer H, Seyberth HW, Lee SW, Ho PC. Pharmacokinetics of different routes of administration of misoprostol. Hum Reprod. 2002 Feb;17(2):332-6. — View Citation

Trinder J, Brocklehurst P, Porter R, Read M, Vyas S, Smith L. Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial). BMJ. 2006 May 27;332(7552):1235-40. Epub 2006 May 17. — View Citation

Wagaarachchi PT, Ashok PW, Narvekar N, Smith NC, Templeton A. Medical management of early fetal demise using a combination of mifepristone and misoprostol. Hum Reprod. 2001 Sep;16(9):1849-53. — View Citation

Wagaarachchi PT, Ashok PW, Smith NC, Templeton A. Medical management of early fetal demise using sublingual misoprostol. BJOG. 2002 Apr;109(4):462-5. — View Citation

Zhang J, Gilles JM, Barnhart K, Creinin MD, Westhoff C, Frederick MM; National Institute of Child Health Human Development (NICHD) Management of Early Pregnancy Failure Trial. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med. 2005 Aug 25;353(8):761-9. — View Citation

Zieman M, Fong SK, Benowitz NL, Banskter D, Darney PD. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol. 1997 Jul;90(1):88-92. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Women With Complete Abortion 24-48hrs After Receiving Medical Treatment for Early Pregnancy Failure.		24-48 hrs	No
Secondary	Complete Abortion at One Week	Complete abortion at one week; uterus demonstrated to be empty on transvaginal ultrasound	3 weeks	No