Spontaneous Abortion
Conditions
Keywords
Spontaneous abortion, Early Pregnancy Failure, Mifepristone, Misoprostol
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.
Interventions
DRUGMisoprostol
DRUGMifepristone
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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) | — |
| Gestational Sac Expulsion by the 30-day Telephone Call | 30 Days | — |
| Uterine Asperation | 30 Days | Surgical removal of the miscarriage. |
Secondary
| Measure | Time frame |
|---|---|
| Frequency of Serious Adverse Events Between Study Arms. | 30 days |
| Adverse Event Reported by Participants | 30 Days |
Countries
United States
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).
Participants by arm
| Arm | Count |
|---|---|
| Misoprostol 800 micrograms of vaginal misoprostol alone
Misoprostol | 151 |
| Misoprostol Plus Mifepristone 800 micrograms vaginal misoprostol, preceded by 200 milligrams oral mifepristone 24 hours prior
Misoprostol
Mifepristone | 149 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Misoprostol Plus Mifepristone | Total | Misoprostol |
|---|---|---|---|
| Age, Customized Participant's age | 30.7 years | 30.4 years | 30.2 years |
| Diagnosis Anembryonic gestation | 40 Participants | 77 Participants | 37 Participants |
| Diagnosis Embryonic of fetal death | 109 Participants | 223 Participants | 114 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 20 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 65 Participants | 132 Participants | 67 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants | 39 Participants | 21 Participants |
| Race (NIH/OMB) White | 57 Participants | 109 Participants | 52 Participants |
| Region of Enrollment United States | 149 participants | 300 participants | 151 participants |
| Sex: Female, Male Female | 149 Participants | 300 Participants | 151 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 151 | 0 / 149 |
| other Total, other adverse events | 115 / 151 | 118 / 149 |
| serious Total, serious adverse events | 3 / 151 | 5 / 149 |
Outcome results
Primary
Gestational Sac Expulsion by the 30-day Telephone Call
Time frame: 30 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Misoprostol | Gestational Sac Expulsion by the 30-day Telephone Call | 113 Participants |
| Misoprostol Plus Mifepristone | Gestational Sac Expulsion by the 30-day Telephone Call | 135 Participants |
Primary
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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Misoprostol | Gestational Sac Expulsion by the Second Follow-up Visit at Day 8 | 111 Participants |
| Misoprostol Plus Mifepristone | Gestational Sac Expulsion by the Second Follow-up Visit at Day 8 | 132 Participants |
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Misoprostol | 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. | 100 Participants |
| Misoprostol Plus Mifepristone | 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. | 124 Participants |
Primary
Uterine Asperation
Surgical removal of the miscarriage.
Time frame: 30 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Misoprostol | Uterine Asperation | 35 Participants |
| Misoprostol Plus Mifepristone | Uterine Asperation | 13 Participants |
Secondary
Adverse Event Reported by Participants
Time frame: 30 Days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Misoprostol | Adverse Event Reported by Participants | 5.6 adverse events |
| Misoprostol Plus Mifepristone | Adverse Event Reported by Participants | 6.1 adverse events |
Secondary
Frequency of Serious Adverse Events Between Study Arms.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Misoprostol | Frequency of Serious Adverse Events Between Study Arms. | 3 Participants |
| Misoprostol Plus Mifepristone | Frequency of Serious Adverse Events Between Study Arms. | 5 Participants |