Pregnancy, Unwanted
Conditions
Keywords
mifepristone, progesterone, abortion
Brief summary
Double-blind randomized trial to evaluate the potential impact of progesterone treatment on early pregnancies exposed to mifepristone.
Detailed description
Medical abortion commonly refers to early pregnancy termination (usually before 10 weeks' gestation) performed without primary surgical intervention and resulting from the use of abortion-inducing medications. The use of medications to cause abortion has been around for almost 70 years but the modern era of medical abortion treatment evolved with the development of mifepristone, a progesterone-receptor blocker with an affinity for the receptor greater than progesterone itself. Medical abortion with mifepristone and misoprostol is highly effective; however, the risk of continuing pregnancy is still present, especially as gestation advances. While most women opt for further treatment in these scenarios, such as surgical aspiration, there are some who decide to continue the pregnancy. Thus, even following treatment, some women do change their mind. No well-done study has evaluated whether such treatment works. Poorly controlled case series are not evidence and systematic reviews of continuing pregnancy rates after mifepristone/prostaglandin analogue treatment failure do not reflect real life outcomes. This study is also a first step to understanding if large studies evaluating mifepristone antagonization with high-dose progesterone are indicated and if placebo-controlled randomized trials can be successfully completed when evaluating this question.
Interventions
All subjects receive mifepristone tablet on treatment day 1.
DRUGmicronized Progesterone
Subjects randomized to progesterone receive treatment starting day 2.
DRUGPlacebo oral capsule
Subjects randomized to placebo receive treatment starting day 2.
Sponsors
Society of Family Planning
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
placebo pills in opaque bottle
Intervention model description
Randomized, double blind, placebo controlled trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Pregnant females 18 years and older at enrollment. 2. Seeking surgical abortion at 44-63 days' gestation on Study day 1. 3. Have received counseling and signed informed consent per UCD standard procedures for surgical abortion. 4. Presence of embryonic gestational cardiac activity on transvaginal ultrasonography. 5. English-speaking 6. Willing to sign informed consent and follow study protocol. 7. Willing to experience potential expulsion of the pregnancy with mifepristone treatment.
Exclusion criteria
1. Medical contraindications to medical abortion. 1. Poorly controlled hypertension (systolic BP \>160 or diastolic BP \>95) 2. Significant anemia - known recent hemoglobin \<9.5 gm/dL 3. Clinically significant cardiovascular disease (angina, valvular disease, arrhythmia, or congestive heart failure) 4. Breastfeeding 5. Coagulopathy or therapeutic coagulation 6. Ultrasound evidence of molar or ectopic pregnancy 7. Chronic systemic corticosteroid use 8. Adrenal disease 9. Sickle cell anemia with frequent/recent crises 10. Glaucoma 2. IUD in place during conception, even if removed. 3. Peanut allergy. 4. Known intolerance of mifepristone or progesterone. 5. Any other condition, that in the opinion of the clinician, would contraindicate mifepristone, progesterone or medical abortion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Continuing Pregnancy Based on Ultrasound Examination | at 14-16 days after mifepristone administration | Pregnancy still in uterus with normal growth and gestational cardiac activity present based on ultrasound examination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expulsion During Follow-up Evaluation | up to 16 days after mifepristone administration | Pregnancy expulsion following mifepristone treatment |
| Number of Participants With Adverse Events During Follow-up Evaluation | up to 16 days after mifepristone administration | Side effects from progesterone/placebo treatment and ability to continued treatment as prescribed |
| Medical Safety During Treatment and Follow-up | up to 16 days after mifepristone administration | Adverse events related to morbidity, e.g. hemorrhage, emergency department visits, emergent dilation and curettage procedures |
| Number of Participants With Change in Serum Progesterone and hCG During Follow-up | up to 16 days after mifepristone administration | Change in serum progesterone and hCG during follow-up evaluation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Progesterone Micronized progesterone 200mg oral capsules starting 24 hours after mifepristone 200mg ingestion (day 1).
Progesterone treatment days 2-4: two capsules twice daily orally. Progesterone treatment days 5-15, 16 or 17: two capsules once daily orally.
Mifepristone 200 MG: All subjects receive mifepristone tablet on treatment day 1.
micronized Progesterone: Subjects randomized to progesterone receive treatment starting day 2. | 6 |
| Placebo Oral Capsule Placebo capsules starting 24 hours after mifepristone 200mg ingestion (day 1). Placebo treatment days 2-4: two capsules twice daily orally. Placebo treatment days 5-15, 16 or 17: two capsules once daily orally.
Mifepristone 200 MG: All subjects receive mifepristone tablet on treatment day 1.
Placebo oral capsule: Subjects randomized to placebo receive treatment starting day 2. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Total | Placebo Oral Capsule | Progesterone |
|---|---|---|---|
| Age, Continuous | 27.3 years | 24.1 years | 29.8 years |
| BMI | 24.6 kg/m^2 | 24.6 kg/m^2 | 24.8 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gestational Age | 52.5 days | 55 days | 49.5 days |
| Gravidity | 4 number of pregnancies | 3.5 number of pregnancies | 4.5 number of pregnancies |
| Obesity | 4 Participants | 2 Participants | 2 Participants |
| Parity | 1 number of deliveries | 0.5 number of deliveries | 1.5 number of deliveries |
| Past mifepristone use | 4 Participants | 3 Participants | 1 Participants |
| Prior progesterone use (n, %) | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 4 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 0 Participants |
| Region of Enrollment United States | 12 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 12 Participants | 6 Participants | 6 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 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 1 / 6 |
| serious Total, serious adverse events | 1 / 6 | 2 / 6 |
Outcome results
Primary
Continuing Pregnancy Based on Ultrasound Examination
Pregnancy still in uterus with normal growth and gestational cardiac activity present based on ultrasound examination
Time frame: at 14-16 days after mifepristone administration
Population: Intention to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Progesterone | Continuing Pregnancy Based on Ultrasound Examination | 4 Participants |
| Placebo Oral Capsule | Continuing Pregnancy Based on Ultrasound Examination | 2 Participants |
Secondary
Expulsion During Follow-up Evaluation
Pregnancy expulsion following mifepristone treatment
Time frame: up to 16 days after mifepristone administration
Population: intention to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Progesterone | Expulsion During Follow-up Evaluation | 1 Participants |
| Placebo Oral Capsule | Expulsion During Follow-up Evaluation | 2 Participants |
Secondary
Medical Safety During Treatment and Follow-up
Adverse events related to morbidity, e.g. hemorrhage, emergency department visits, emergent dilation and curettage procedures
Time frame: up to 16 days after mifepristone administration
Population: intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone | Medical Safety During Treatment and Follow-up | Emergency Room Visit | 1 participants |
| Progesterone | Medical Safety During Treatment and Follow-up | Emergent D&C | 0 participants |
| Progesterone | Medical Safety During Treatment and Follow-up | Hemorrhage | 1 participants |
| Progesterone | Medical Safety During Treatment and Follow-up | Side effects - request D&C | 1 participants |
| Progesterone | Medical Safety During Treatment and Follow-up | Transfusion | 0 participants |
| Placebo Oral Capsule | Medical Safety During Treatment and Follow-up | Side effects - request D&C | 1 participants |
| Placebo Oral Capsule | Medical Safety During Treatment and Follow-up | Hemorrhage | 2 participants |
| Placebo Oral Capsule | Medical Safety During Treatment and Follow-up | Emergency Room Visit | 2 participants |
| Placebo Oral Capsule | Medical Safety During Treatment and Follow-up | Transfusion | 1 participants |
| Placebo Oral Capsule | Medical Safety During Treatment and Follow-up | Emergent D&C | 2 participants |
Secondary
Number of Participants With Adverse Events During Follow-up Evaluation
Side effects from progesterone/placebo treatment and ability to continued treatment as prescribed
Time frame: up to 16 days after mifepristone administration
Population: increased to severe at any time during follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Nausea | 2 participants |
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Vomiting | 2 participants |
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Mastalgia | 0 participants |
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Tiredness | 0 participants |
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Mood changes | 1 participants |
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Reflux | 0 participants |
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Dizziness | 0 participants |
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Bleeding | 1 participants |
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Spotting | 0 participants |
| Progesterone | Number of Participants With Adverse Events During Follow-up Evaluation | Cramping | 0 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Bleeding | 3 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Nausea | 1 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Reflux | 0 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Vomiting | 0 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Cramping | 0 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Mastalgia | 0 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Dizziness | 0 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Tiredness | 1 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Spotting | 0 participants |
| Placebo Oral Capsule | Number of Participants With Adverse Events During Follow-up Evaluation | Mood changes | 0 participants |
Secondary
Number of Participants With Change in Serum Progesterone and hCG During Follow-up
Change in serum progesterone and hCG during follow-up evaluation
Time frame: up to 16 days after mifepristone administration
Population: intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone | Number of Participants With Change in Serum Progesterone and hCG During Follow-up | Progesterone increase from baseline at FU 1 | 5 participants |
| Progesterone | Number of Participants With Change in Serum Progesterone and hCG During Follow-up | Progesterone decrease from baseline at FU 1 | 0 participants |
| Progesterone | Number of Participants With Change in Serum Progesterone and hCG During Follow-up | hCG increase from baseline at FU 1 | 4 participants |
| Progesterone | Number of Participants With Change in Serum Progesterone and hCG During Follow-up | hCG decrease from baseline at FU 1 | 1 participants |
| Placebo Oral Capsule | Number of Participants With Change in Serum Progesterone and hCG During Follow-up | hCG decrease from baseline at FU 1 | 3 participants |
| Placebo Oral Capsule | Number of Participants With Change in Serum Progesterone and hCG During Follow-up | Progesterone increase from baseline at FU 1 | 2 participants |
| Placebo Oral Capsule | Number of Participants With Change in Serum Progesterone and hCG During Follow-up | hCG increase from baseline at FU 1 | 3 participants |
| Placebo Oral Capsule | Number of Participants With Change in Serum Progesterone and hCG During Follow-up | Progesterone decrease from baseline at FU 1 | 2 participants |