Comparative Effectiveness of Pregnancy Failure Management Regimens (PreFaiR)

• ClinicalTrials.gov Identifier: NCT02012491
• Recruitment Status: Completed
• First Posted: December 16, 2013
• Results First Posted: December 21, 2018
• Last Update Posted: July 18, 2019
• Sponsor: University of Pennsylvania
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): University of Pennsylvania

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Spontaneous Abortion
• Interventions: Drug: Misoprostol; Drug: Mifepristone
• Enrollment: 300

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).
Pre-assignment Details

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
Reason Not Completed
Lost to Follow-up	1	0
Protocol Violation	0	1
Withdrawal by Subject	1	0

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 Number of Baseline Participants		151	149	300
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Mean (Full Range); Unit of measure: Years
Participant's age	Number Analyzed	151 participants	149 participants	300 participants
		30.2; (18 to 46)	30.7; (18 to 46)	30.4; (18 to 46)
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	151 participants	149 participants	300 participants
	Female	151 100.0%	149 100.0%	300 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Description: Only females where included in this study.
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	151 participants	149 participants	300 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	11 7.3%	9 6.0%	20 6.7%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	67 44.4%	65 43.6%	132 44.0%
	White	52 34.4%	57 38.3%	109 36.3%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	21 13.9%	18 12.1%	39 13.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	151 participants	149 participants	300 participants
		151	149	300
Diagnosis; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	151 participants	149 participants	300 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.
Description	[Not Specified]
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
Overall Number of Participants Analyzed	149	148
Measure Type: Count of Participants; Unit of Measure: Participants
	100 67.1%	124 83.8%

2. Primary Outcome

Title	Gestational Sac Expulsion by the Second Follow-up Visit at Day 8
Description	[Not Specified]
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
Overall Number of Participants Analyzed	149	148
Measure Type: Count of Participants; Unit of Measure: Participants
	111 74.5%	132 89.2%

3. Primary Outcome

Title	Gestational Sac Expulsion by the 30-day Telephone Call
Description	[Not Specified]
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
Overall Number of Participants Analyzed	149	148
Measure Type: Count of Participants; Unit of Measure: Participants
	113 75.8%	135 91.2%

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
Overall Number of Participants Analyzed	149	148
Measure Type: Count of Participants; Unit of Measure: Participants
	35 23.5%	13 8.8%

5. Secondary Outcome

Title	Frequency of Serious Adverse Events Between Study Arms.
Description	[Not Specified]
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
Overall Number of Participants Analyzed	151	149
Measure Type: Count of Participants; Unit of Measure: Participants
	3 2.0%	5 3.4%

6. Secondary Outcome

Title	Adverse Event Reported by Participants
Description	[Not Specified]
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
Overall Number of Participants Analyzed	151	149
Mean (Full Range); Unit of Measure: adverse events
	5.6; (0 to 843)	6.1; (0 to 904)

Adverse Events

Time Frame	Adverse events were collected over a 30 day time frame
Adverse Event Reporting 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
All-Cause Mortality
	Misoprostol		Misoprostol Plus Mifepristone
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/151 (0.00%)		0/149 (0.00%)
Serious Adverse Events
	Misoprostol		Misoprostol Plus Mifepristone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/151 (1.99%)		5/149 (3.36%)
Blood and lymphatic system disorders
Bleeding resulting in blood transfusion †	1/151 (0.66%)	1	3/149 (2.01%)	3
Reproductive system and breast disorders
Pelvic Infection †	2/151 (1.32%)	2	2/149 (1.34%)	2
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Misoprostol		Misoprostol Plus Mifepristone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/151 (76.16%)		118/149 (79.19%)
General disorders
Fatigue †	115/151 (76.16%)		118/149 (79.19%)
† Indicates events were collected by systematic assessment

Limitations and 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.

Results Point of Contact

• Name/Title: Dr. Courtney Schreiber
• Organization: University of Pennsylvania
• Phone: 215-615-5234
• EMail: Courtney.Schreiber@uphs.upenn.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Roe AH, McAllister A, Flynn AN, Martin B, Jiang E, Koelper N, Schreiber CA. The effect of mifepristone pretreatment on bleeding and pain during medical management of early pregnancy loss. Contraception. 2021 Oct;104(4):432-436. doi: 10.1016/j.contraception.2021.04.023. Epub 2021 Apr 28.

Shorter JM, Koelper N, Sonalkar S, Oquendo MA, Sammel MD, Schreiber CA. Racial Disparities in Mental Health Outcomes Among Women With Early Pregnancy Loss. Obstet Gynecol. 2021 Jan 1;137(1):156-163. doi: 10.1097/AOG.0000000000004212.

Sonalkar S, Koelper N, Creinin MD, Atrio JM, Sammel MD, McAllister A, Schreiber CA. Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial. Am J Obstet Gynecol. 2020 Oct;223(4):551.e1-551.e7. doi: 10.1016/j.ajog.2020.04.006. Epub 2020 Apr 17.

Nagendra D, Koelper N, Loza-Avalos SE, Sonalkar S, Chen M, Atrio J, Schreiber CA, Harvie HS. Cost-effectiveness of Mifepristone Pretreatment for the Medical Management of Nonviable Early Pregnancy: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2020 Mar 2;3(3):e201594. doi: 10.1001/jamanetworkopen.2020.1594.

Clement EG, Horvath S, McAllister A, Koelper NC, Sammel MD, Schreiber CA. The Language of First-Trimester Nonviable Pregnancy: Patient-Reported Preferences and Clarity. Obstet Gynecol. 2019 Jan;133(1):149-154. doi: 10.1097/AOG.0000000000002997.

Schreiber CA, Creinin MD, Atrio J, Sonalkar S, Ratcliffe SJ, Barnhart KT. Mifepristone Pretreatment for the Medical Management of Early Pregnancy Loss. N Engl J Med. 2018 Jun 7;378(23):2161-2170. doi: 10.1056/NEJMoa1715726.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02012491
• Other Study ID Numbers: 818434; 1R01HD071920-01A1 ( U.S. NIH Grant/Contract )
• First Submitted: December 10, 2013
• First Posted: December 16, 2013
• Results First Submitted: August 28, 2018
• Results First Posted: December 21, 2018
• Last Update Posted: July 18, 2019