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

• Sponsor: Boston University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00468299
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 20
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Early Pregnancy Failure; Miscarriage; Fetal Demise; Anembryonic Pregnancy	Drug: Misoprostol and placebo; Drug: Mifepristone and misoprostol	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Treatment of Early Pregnancy Failure
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Misoprostol and placebo Women in this arm receive placebo and misoprostol 800 mcg buccally	Drug: Misoprostol and placebo; Women in this group receive 800 mcg misoprostol plus a placebo
Experimental: Mifepristone and misoprostol Womwn in this group receive mifepristone 200 mg orally and misoprostol 800 mcg buccally	Drug: Mifepristone and misoprostol; This group receives mifepristone 200 mg orally; followed by 800 mcg misoprostol bucally

Outcome Measures

Primary Outcome Measures

1. Number of Women With Complete Abortion 24-48hrs After Receiving Medical Treatment for Early Pregnancy Failure. [24-48 hrs]

Secondary Outcome Measures

1. Complete Abortion at One Week [3 weeks]

   Complete abortion at one week; uterus demonstrated to be empty on transvaginal ultrasound

Eligibility Criteria

Criteria

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

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

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

• ClinicalTrials.gov Identifier: NCT00468299
• Other Study ID Numbers: H-25999
• First Posted: May 2, 2007
• Last Update Posted: Jul 21, 2011
• Last Verified: Jun 1, 2011

• Keywords provided by , ,: early; pregnancy; failure; mifepristone; misoprostol; buccal; miscarriage; fetal; demise; anembryonic; progesterone
• Additional relevant MeSH terms: Abortion, Spontaneous; Fetal Death; Misoprostol; Mifepristone

Study Results

Participant Flow

Arm/Group Title	Misoprostol and Placebo	Mifepristone and Misoprostol
Arm/Group Description	Women in this groups received misoprostol (800 mcg buccally) plus a placebo for treatment of early pregnancy failure.	Women in this group received mifepristone 200 mg orally followed by misoprostol 800 mcg buccally
Period Title: Overall Study
STARTED	9	8
COMPLETED	9	7
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Misoprostol and Placebo	Mifepristone and Misoprostol	Total
Arm/Group Description	Women in this groups received misoprostol (800 mcg buccally) plus a placebo for treatment of early pregnancy failure.	Women in this group received mifepristone 200 mg orally followed by misoprostol 800 mcg buccally	Total of all reporting groups
Overall Participants	9	8	17
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	9 100%	8 100%	17 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28 (4)	29 (4)	28 (3)
Sex: Female, Male (Count of Participants)
Female	9 100%	8 100%	17 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%	8 100%	17 100%

Outcome Measures

1. Primary Outcome

Title	Number of Women With Complete Abortion 24-48hrs After Receiving Medical Treatment for Early Pregnancy Failure.
Time Frame	24-48 hrs

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol and Placebo	Mifepristone and Misoprostol
Arm/Group Description	Women in this groups received misoprostol (800 mcg buccally) plus a placebo for treatment of early pregnancy failure.	Women in this group received mifepristone 200 mg orally followed by misoprostol 800 mcg buccally
Measure Participants	9	8
Number [participants]	5 55.6%	5 62.5%

2. Secondary Outcome

Title	Complete Abortion at One Week
Description	Complete abortion at one week; uterus demonstrated to be empty on transvaginal ultrasound
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Misoprostol and Placebo	Mifepristone and Misoprostol
Arm/Group Description	Women received a placebo followed by misoprostol 800 mcg buccally	Women received mifeppristone 200 mg orally followed ny misoprostol 800 mcg buccally
Measure Participants	9	8
Number [participants]	6 66.7%	7 87.5%

Adverse Events

Arm/Group Title	Misoprostol and Placebo		Mifepristone and Misoprostol
Arm/Group Description	Women in this groups received misoprostol (800 mcg buccally) plus a placebo for treatment of early pregnancy failure.		Women in this group received mifepristone 200 mg orally followed by misoprostol 800 mcg buccally
All Cause Mortality
	Misoprostol and Placebo		Mifepristone and Misoprostol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Misoprostol and Placebo		Mifepristone and Misoprostol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Misoprostol and Placebo		Mifepristone and Misoprostol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/8 (0%)

Limitations/Caveats

The study was terminated because of poor enrollment. Few eligible women were referred.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.