Blocking Mifepristone Action With Progesterone

• ClinicalTrials.gov Identifier: NCT03774745
• Recruitment Status: Terminated
• First Posted: December 13, 2018
• Last Update Posted: August 27, 2019
• Sponsor: University of California, Davis
• Collaborator: Society of Family Planning
• Information provided by (Responsible Party): University of California, Davis

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pregnancy, Unwanted	Drug: Mifepristone 200 MG; Drug: micronized Progesterone; Drug: Placebo oral capsule	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double blind, placebo controlled trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: placebo pills in opaque bottle
• Primary Purpose: Treatment
• Official Title: A Randomized Trial of Mifepristone Antagonization With High-Dose Progesterone to Prevent Medical Abortion
• Actual Study Start Date: February 11, 2019
• Actual Primary Completion Date: July 29, 2019
• Actual Study Completion Date: August 15, 2019

Arms and Interventions

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 Name: Mifeprex; Drug: micronized Progesterone; Subjects randomized to progesterone receive treatment starting day 2.; Other Name: 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 Name: Mifeprex; Drug: Placebo oral capsule; Subjects randomized to placebo receive treatment starting day 2.; Other Name: Placebo (for micronized progesterone)

Outcome Measures

Primary Outcome Measures :

1. Continuing pregnancy based on ultrasound examination [ Time Frame: at 14-16 days after mifepristone administration ]
   Pregnancy still in uterus with normal growth and gestational cardiac activity present based on ultrasound examination

Secondary Outcome Measures :

1. Expulsion during follow-up evaluation [ Time Frame: up to 16 days after mifepristone administration ]
   Pregnancy expulsion following mifepristone treatment
2. Adverse events during follow-up evaluation [ Time Frame: up to 16 days after mifepristone administration ]
   Side effects from progesterone/placebo treatment and ability to continued treatment as prescribed
3. Medical safety during treatment and follow-up [ Time Frame: up to 16 days after mifepristone administration ]
   Adverse events related to morbidity, e.g. hemorrhage, emergency department visits, emergent dilation and curettage procedures
4. Change in serum progesterone and hCG during follow-up evaluation [ Time Frame: up to 16 days after mifepristone administration ]
   Change in serum progesterone and hCG during follow-up evaluation
5. Pathology evaluation (exploratory) [ Time Frame: up to 16 days after mifepristone administration ]
   Pathologic changes in products of conception and differences between progesterone and placebo arms in a subset of women who have an aspiration procedure during or at the end of treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Biologic females who are pregnant
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, California

Planned Parenthood Mar Monte

Sacramento, California, United States, 95816

University of California, Davis

Sacramento, California, United States, 95817

Family Planning Associates

Sacramento, California, United States, 95825

Sponsors and Collaborators

University of California, Davis

Society of Family Planning

Investigators

• Principal Investigator: Mitchell D Creinin, MD; University of California, Davis

More Information

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT03774745 History of Changes
• Other Study ID Numbers: 1353650
• First Posted: December 13, 2018
• Last Update Posted: August 27, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Sharing de-identified data will be considered upon individual request

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of California, Davis:

mifepristone; progesterone; abortion

Additional relevant MeSH terms:

Mifepristone; Progesterone; Progestins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Abortifacient Agents, Steroidal; Abortifacient Agents; Reproductive Control Agents; Contraceptives, Oral, Synthetic; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Hormone Antagonists; Luteolytic Agents; Menstruation-Inducing Agents