PreFaiR: Comparative Effectiveness of Pregnancy Failure Management Regimens

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT02012491
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 300
• Locations: 3
• Arms: 2
• Duration (Months): 65.4
• Patients Per Site: 100
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The purpose of the study is to compare the effectiveness of combination treatment (mifepristone premedication plus single-dose misoprostol) to single-dose misoprostol (standard of care) for the management of early pregnancy failure.

Condition or Disease	Intervention/Treatment	Phase
Spontaneous Abortion	Drug: Misoprostol; Drug: Mifepristone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparative Effectiveness of Pregnancy Failure Management Regimens
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: May 15, 2017
• Actual Study Completion Date: Jun 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: misoprostol plus mifepristone 800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior	Drug: Misoprostol; Other Names: Cytotec ; Drug: Mifepristone; Other Names: Mifeprex
Active Comparator: misoprostol 800 micrograms of vaginal misoprostol alone	Drug: Misoprostol; Other Names: Cytotec

Outcome Measures

Primary Outcome Measures

1. Gestational Sac Expulsion With One Treatment Dose on Day 3 (Visit 2) and no Need for Additional Medical or Surgical Intervention Within 30 Days of Treatment. [Day 3 (visit 2) and up to 30 days following visit (to ensure surgical measures were not done]

2. Gestational Sac Expulsion by the Second Follow-up Visit at Day 8 [Day 8 (visit 3) and up to 30 day to ensure additional measures were not done (surgical)]

3. Gestational Sac Expulsion by the 30-day Telephone Call [30 Days]

4. Uterine Asperation [30 Days]

   Surgical removal of the miscarriage.

Secondary Outcome Measures

1. Frequency of Serious Adverse Events Between Study Arms. [30 days]

2. Adverse Event Reported by Participants [30 Days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• between 5 and 12 completed weeks gestation

• 18 years or older

• hemodynamically stable

• confirmed diagnosis of intrauterine embryonic/fetal demise or anembryonic gestation (ultrasound examination demonstrates a fetal pole without cardiac activity measuring between 5.3 and 40 mm or an abnormal growth pattern diagnostic of early pregnancy failure)

• willing and able to give informed consent

Exclusion Criteria:

• diagnosis of incomplete or inevitable abortion (absent gestational sac and/or active bleeding, open cervical os)

• contraindication to mifepristone (chronic corticosteroid administration, adrenal disease)

• contraindication to misoprostol (glaucoma, mitral stenosis, sickle cell anemia, or known allergy to prostaglandin)

• cardiovascular disease (angina, valvular disease, arrhythmia, or cardiac failure)

• most recent hemoglobin <9.5 g/dL

• diagnosis of porphyria

• known clotting defect or receiving anticoagulants

• pregnancy with an intrauterine device (IUD) in place

• breastfeeding during the first 7 days of study participation

• unwilling to comply with the study protocol and visit schedule

• any evidence of viable pregnancy

• possibility of ectopic pregnancy

• known or suspected pelvic infection

• concurrent participation in any other interventional trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Davis Medical Center	Sacramento	California	United States	95817
2	Montefiore Medical Center	Bronx	New York	United States	10461
3	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Courtney A Schreiber, MD, MPH, University of Pennsylvania
• Principal Investigator: Mitchell Creinin, MD, University of California, Davis

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 7, 2017

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02012491
• Other Study ID Numbers: 818434; 1R01HD071920-01A1
• First Posted: Dec 16, 2013
• Last Update Posted: Jul 18, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by University of Pennsylvania: Spontaneous abortion; Early Pregnancy Failure; Mifepristone; Misoprostol
• Additional relevant MeSH terms: Abortion, Spontaneous; Misoprostol; Mifepristone

Study Results

Participant Flow

Recruitment Details	We randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, orally, followed by 800 μg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 μg of misoprostol alone, administered vaginally (misoprostol-alone group).

Arm/Group Title	Misoprostol	Misoprostol Plus Mifepristone
Arm/Group Description	800 micrograms of vaginal misoprostol alone Misoprostol	800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior Misoprostol Mifepristone
Period Title: Overall Study
STARTED	151	149
COMPLETED	149	148
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Misoprostol	Misoprostol Plus Mifepristone	Total
Arm/Group Description	800 micrograms of vaginal misoprostol alone Misoprostol	800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior Misoprostol Mifepristone	Total of all reporting groups
Overall Participants	151	149	300
Age, Customized (years) [Mean (Full Range) ]
Participant's age	30.2	30.7	30.4
Sex: Female, Male (Count of Participants)
Female	151 100%	149 100%	300 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	11 7.3%	9 6%	20 6.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	67 44.4%	65 43.6%	132 44%
White	52 34.4%	57 38.3%	109 36.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	21 13.9%	18 12.1%	39 13%
Region of Enrollment (participants) [Number]
United States	151 100%	149 100%	300 100%
Diagnosis (Count of Participants)
Anembryonic gestation	37 24.5%	40 26.8%	77 25.7%
Embryonic of fetal death	114 75.5%	109 73.2%	223 74.3%

Outcome Measures

1. Primary Outcome

Title	Gestational Sac Expulsion With One Treatment Dose on Day 3 (Visit 2) and no Need for Additional Medical or Surgical Intervention Within 30 Days of Treatment.
Time Frame	Day 3 (visit 2) and up to 30 days following visit (to ensure surgical measures were not done

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol	Misoprostol Plus Mifepristone
Arm/Group Description	800 micrograms of vaginal misoprostol alone Misoprostol	800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior Misoprostol Mifepristone
Measure Participants	149	148
Count of Participants [Participants]	100 66.2%	124 83.2%

2. Primary Outcome

Title	Gestational Sac Expulsion by the Second Follow-up Visit at Day 8
Time Frame	Day 8 (visit 3) and up to 30 day to ensure additional measures were not done (surgical)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol	Misoprostol Plus Mifepristone
Arm/Group Description	800 micrograms of vaginal misoprostol alone Misoprostol	800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior Misoprostol Mifepristone
Measure Participants	149	148
Count of Participants [Participants]	111 73.5%	132 88.6%

3. Primary Outcome

Title	Gestational Sac Expulsion by the 30-day Telephone Call
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol	Misoprostol Plus Mifepristone
Arm/Group Description	800 micrograms of vaginal misoprostol alone Misoprostol	800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior Misoprostol Mifepristone
Measure Participants	149	148
Count of Participants [Participants]	113 74.8%	135 90.6%

4. Primary Outcome

Title	Uterine Asperation
Description	Surgical removal of the miscarriage.
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol	Misoprostol Plus Mifepristone
Arm/Group Description	800 micrograms of vaginal misoprostol alone Misoprostol	800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior Misoprostol Mifepristone
Measure Participants	149	148
Count of Participants [Participants]	35 23.2%	13 8.7%

5. Secondary Outcome

Title	Frequency of Serious Adverse Events Between Study Arms.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol	Misoprostol Plus Mifepristone
Arm/Group Description	800 micrograms of vaginal misoprostol alone Misoprostol	800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior Misoprostol Mifepristone
Measure Participants	151	149
Count of Participants [Participants]	3 2%	5 3.4%

6. Secondary Outcome

Title	Adverse Event Reported by Participants
Time Frame	30 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Misoprostol	Misoprostol Plus Mifepristone
Arm/Group Description	800 micrograms of vaginal misoprostol alone Misoprostol	800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior Misoprostol Mifepristone
Measure Participants	151	149
Mean (Full Range) [adverse events]	5.6	6.1

Adverse Events

Time Frame	Adverse events were collected over a 30 day time frame
Arm/Group Title	Misoprostol		Misoprostol Plus Mifepristone
Arm/Group Description	800 micrograms of vaginal misoprostol alone Misoprostol		800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior Misoprostol Mifepristone
All Cause Mortality
	Misoprostol		Misoprostol Plus Mifepristone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/151 (0%)		0/149 (0%)
Serious Adverse Events
	Misoprostol		Misoprostol Plus Mifepristone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/151 (2%)		5/149 (3.4%)
Blood and lymphatic system disorders
Bleeding resulting in blood transfusion	1/151 (0.7%)	1	3/149 (2%)	3
Reproductive system and breast disorders
Pelvic Infection	2/151 (1.3%)	2	2/149 (1.3%)	2
Other (Not Including Serious) Adverse Events
	Misoprostol		Misoprostol Plus Mifepristone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/151 (76.2%)		118/149 (79.2%)
General disorders
Fatigue	115/151 (76.2%)		118/149 (79.2%)

Limitations/Caveats

[Not Specified]

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.