MiMi: A Randomized Trial of Mifepristone and Misoprostol for Treatment of Early Pregnancy Failure - Full Text View

Sponsored by:	Boston University
Information provided by:	Boston University
ClinicalTrials.gov Identifier:	NCT00468299

Purpose

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.

Condition	Intervention
Early Pregnancy Failure Miscarriage Fetal Demise Anembryonic Pregnancy	Drug: mifepristone Drug: placebo

MedlinePlus related topics: Pregnancy Loss

Drug Information available for: Misoprostol Mifepristone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Efficacy Study
Official Title:	Treatment of Early Pregnancy Failure

Further study details as provided by Boston University:

Primary Outcome Measures:

Rate of complete abortion 24-48hrs after receiving medical treatment for early pregnancy failure. [ Time Frame: 24-48 hrs ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Secondary outcomes include: rate of complete abortion at one week, time to expulsion of products of conception, correlation of abortion rates to serum progesterone levels and type of pregnancy failure, number of bleeding days and patient satisfaction [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	108
Study Start Date:	April 2007
Estimated Study Completion Date:	May 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator	Drug: placebo this group does not receive mifepristone
2: Experimental Receives mifepristone and misoprostol	Drug: mifepristone 200 mg mifepristone given along with 800 mcg misoprostol

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years to 64 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468299

Locations

United States, Massachusetts
Boston University
Boston, Massachusetts, United States, 02118

Sponsors and Collaborators

Boston University

Investigators

Principal Investigator:	Sarah J Betstadt, MD	Boston University
Study Director:	Olivera Vragovic, MBA	Boston University

More Information

Publications:

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.

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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.

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.

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.

Responsible Party:	Boston University ( Sarah Betstadt, MD )
Study ID Numbers:	H-25999
Study First Received:	May 1, 2007
Last Updated:	October 3, 2008
ClinicalTrials.gov Identifier:	NCT00468299 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Boston University:

early
pregnancy
failure
mifepristone
misoprostol
buccal

miscarriage
fetal
demise
anembryonic
progesterone

Study placed in the following topic categories:

Pregnancy Complications
Progesterone
Contraceptive Agents
Hormone Antagonists
Contraceptives, Oral
Misoprostol

Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents, Female
Mifepristone
Abortion, Spontaneous
Contraceptives, Postcoital
Hormones

Additional relevant MeSH terms:

Abortifacient Agents, Steroidal
Contraceptives, Postcoital, Synthetic
Pregnancy Complications
Oxytocics
Contraceptive Agents
Hormone Antagonists
Misoprostol
Contraceptives, Oral
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents, Female

Mifepristone
Reproductive Control Agents
Abortifacient Agents, Nonsteroidal
Luteolytic Agents
Contraceptives, Postcoital
Pharmacologic Actions
Therapeutic Uses
Anti-Ulcer Agents
Abortifacient Agents
Menstruation-Inducing Agents
Contraceptives, Oral, Synthetic
Abortion, Spontaneous

ClinicalTrials.gov processed this record on May 06, 2009