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

NCT ID: NCT00468299

Last Updated: 2011-07-21

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-30

Study Completion Date

2008-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Early Pregnancy Failure Miscarriage Fetal Demise Anembryonic Pregnancy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Misoprostol and placebo

Women in this arm receive placebo and misoprostol 800 mcg buccally

Group Type ACTIVE_COMPARATOR

Misoprostol and placebo

Intervention Type DRUG

Women in this group receive 800 mcg misoprostol plus a placebo

Mifepristone and misoprostol

Womwn in this group receive mifepristone 200 mg orally and misoprostol 800 mcg buccally

Group Type EXPERIMENTAL

Mifepristone and misoprostol

Intervention Type DRUG

This group receives mifepristone 200 mg orally; followed by 800 mcg misoprostol bucally

Interventions

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Misoprostol and placebo

Women in this group receive 800 mcg misoprostol plus a placebo

Intervention Type DRUG

Mifepristone and misoprostol

This group receives mifepristone 200 mg orally; followed by 800 mcg misoprostol bucally

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Boston University

OTHER

Sponsor Role lead

Responsible Party

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University of Rochester Medical Center

Principal Investigators

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Sarah J Betstadt, MD

Role: PRINCIPAL_INVESTIGATOR

Boston University

Olivera Vragovic, MBA

Role: STUDY_DIRECTOR

Boston University

Locations

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Boston University

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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. doi: 10.1093/humrep/deh049.

Reference Type BACKGROUND
PMID: 14747165 (View on PubMed)

Creinin MD, Schwartz JL, Guido RS, Pymar HC. Early pregnancy failure--current management concepts. Obstet Gynecol Surv. 2001 Feb;56(2):105-13. doi: 10.1097/00006254-200102000-00024.

Reference Type BACKGROUND
PMID: 11219590 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7920940 (View on PubMed)

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. doi: 10.1016/j.ajog.2005.05.010.

Reference Type BACKGROUND
PMID: 16202723 (View on PubMed)

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. doi: 10.1097/01.AOG.0000230398.32794.9d.

Reference Type BACKGROUND
PMID: 16946218 (View on PubMed)

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. doi: 10.1016/j.contraception.2005.05.017. Epub 2005 Aug 9.

Reference Type BACKGROUND
PMID: 16246656 (View on PubMed)

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. doi: 10.1111/j.1471-0528.1997.tb12075.x.

Reference Type BACKGROUND
PMID: 9307543 (View on PubMed)

Schaff EA, DiCenzo R, Fielding SL. Comparison of misoprostol plasma concentrations following buccal and sublingual administration. Contraception. 2005 Jan;71(1):22-5. doi: 10.1016/j.contraception.2004.06.014.

Reference Type BACKGROUND
PMID: 15639067 (View on PubMed)

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. doi: 10.1016/j.fertnstert.2006.03.032.

Reference Type BACKGROUND
PMID: 17027362 (View on PubMed)

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. doi: 10.1093/humrep/17.2.332.

Reference Type BACKGROUND
PMID: 11821273 (View on PubMed)

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. doi: 10.1136/bmj.38828.593125.55. Epub 2006 May 17.

Reference Type BACKGROUND
PMID: 16707509 (View on PubMed)

Wagaarachchi PT, Ashok PW, Smith NC, Templeton A. Medical management of early fetal demise using sublingual misoprostol. BJOG. 2002 Apr;109(4):462-5. doi: 10.1111/j.1471-0528.2002.01075.x.

Reference Type BACKGROUND
PMID: 12013170 (View on PubMed)

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. doi: 10.1093/humrep/16.9.1849.

Reference Type BACKGROUND
PMID: 11527887 (View on PubMed)

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. doi: 10.1056/NEJMoa044064.

Reference Type BACKGROUND
PMID: 16120856 (View on PubMed)

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. doi: 10.1016/S0029-7844(97)00111-7.

Reference Type BACKGROUND
PMID: 9207820 (View on PubMed)

Other Identifiers

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H-25999

Identifier Type: -

Identifier Source: org_study_id

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