Blocking Mifepristone Action With Progesterone

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

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

Study Overview

• Status: Terminated
• Conditions: Pregnancy, Unwanted
• Intervention / Treatment: Drug: Mifepristone 200 MG; Drug: micronized Progesterone; Drug: Placebo oral capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • Sacramento, California, United States, 95816
      • Planned Parenthood Mar Monte
    • Sacramento, California, United States, 95825
      • Family Planning Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Mifepristone 200 MG; All subjects receive mifepristone tablet on treatment day 1.; Other Names: Mifeprex; Drug: micronized Progesterone; Subjects randomized to progesterone receive treatment starting day 2.; Other Names: Prometrium
PLACEBO_COMPARATOR: 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.	Drug: Mifepristone 200 MG; All subjects receive mifepristone tablet on treatment day 1.; Other Names: Mifeprex; Drug: Placebo oral capsule; Subjects randomized to placebo receive treatment starting day 2.; Other Names: Placebo (for micronized progesterone)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: Society of Family Planning
• Investigators: Principal Investigator: Mitchell D Creinin, MD, University of California, Davis

Publications and helpful links

General Publications

• Creinin MD, Hou MY, Dalton L, Steward R, Chen MJ. Mifepristone Antagonization With Progesterone to Prevent Medical Abortion: A Randomized Controlled Trial. Obstet Gynecol. 2020 Jan;135(1):158-165. doi: 10.1097/AOG.0000000000003620.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 11, 2019
• Primary Completion (ACTUAL): July 29, 2019
• Study Completion (ACTUAL): August 15, 2019

Study Registration Dates

• First Submitted: December 11, 2018
• First Submitted That Met QC Criteria: December 11, 2018
• First Posted (ACTUAL): December 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: progesterone; mifepristone; abortion
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Abortifacient Agents; Luteolytic Agents; Abortifacient Agents, Steroidal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Menstruation-Inducing Agents; Progestins; Mifepristone; Progesterone
• Other Study ID Numbers: 1353650

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Sharing de-identified data will be considered upon individual request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No