Blocking Mifepristone Action With Progesterone

Study Overview
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Brief Summary
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Double-blind randomized trial to evaluate the potential impact of progesterone treatment on early pregnancies exposed to mifepristone.

Detailed Description
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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.

Official Title
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A Randomized Trial of Mifepristone Antagonization With High-Dose Progesterone to Prevent Medical Abortion

Conditions
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Pregnancy, Unwanted

Intervention / Treatment
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* Drug: Mifepristone 200 MG
* Drug: micronized Progesterone
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant females 18 years and older at enrollment. Seeking surgical abortion at 44-63 days' gestation on Study day 1. Have received counseling and signed informed consent per UCD standard procedures for surgical abortion. Presence of embryonic gestational cardiac activity on transvaginal ultrasonography. English-speaking Willing to sign informed consent and follow study protocol. Willing to experience potential expulsion of the pregnancy with mifepristone treatment. Exclusion Criteria: Medical contraindications to medical abortion. Poorly controlled hypertension (systolic BP >160 or diastolic BP >95) Significant anemia - known recent hemoglobin <9.5 gm/dL Clinically significant cardiovascular disease (angina, valvular disease, arrhythmia, or congestive heart failure) Breastfeeding Coagulopathy or therapeutic coagulation Ultrasound evidence of molar or ectopic pregnancy Chronic systemic corticosteroid use Adrenal disease Sickle cell anemia with frequent/recent crises Glaucoma IUD in place during conception, even if removed. Peanut allergy. Known intolerance of mifepristone or progesterone. Any other condition, that in the opinion of the clinician, would contraindicate mifepristone, progesterone or medical abortion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double blind, placebo controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Progesterone<br>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. | Drug: Mifepristone 200 MG<br>* All subjects receive mifepristone tablet on treatment day 1.<br>* Other names: Mifeprex;Drug: micronized Progesterone<br>* Subjects randomized to progesterone receive treatment starting day 2.<br>* Other names: Prometrium;|
| Placebo Comparator: Placebo oral capsule<br>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. | Drug: Mifepristone 200 MG<br>* All subjects receive mifepristone tablet on treatment day 1.<br>* Other names: Mifeprex;Drug: Placebo oral capsule<br>* Subjects randomized to placebo receive treatment starting day 2.<br>* Other names: Placebo (for micronized progesterone);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuing Pregnancy Based on Ultrasound Examination | Pregnancy still in uterus with normal growth and gestational cardiac activity present based on ultrasound examination | at 14-16 days after mifepristone administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expulsion During Follow-up Evaluation | Pregnancy expulsion following mifepristone treatment | up to 16 days after mifepristone administration | 
| Number of Participants With Adverse Events During Follow-up Evaluation | Side effects from progesterone/placebo treatment and ability to continued treatment as prescribed | up to 16 days after mifepristone administration | 
| Medical Safety During Treatment and Follow-up | Adverse events related to morbidity, e.g. hemorrhage, emergency department visits, emergent dilation and curettage procedures | up to 16 days after mifepristone administration | 
| Number of Participants With Change in Serum Progesterone and hCG During Follow-up | Change in serum progesterone and hCG during follow-up evaluation | up to 16 days after mifepristone administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mifepristone, progesterone, abortion