The Misoprostol-Only Regimen Evidence Study

This is a randomized controlled trial comparing misoprostol-only (3-4 doses x 800μg misoprostol sublingually every 3 hours) (Arm 2) to the combined regimen (<64 days: mifepristone (200mg orally) followed 24-48 hours later by misoprostol (800μg b/v) with a second dose of misoprostol (800μg b/v) taken 3 hours later only for those 64-77 days) (Arm 1). The combined regimen is the standard of care for medication abortion in the United States, and both regimens are widely used across the globe for termination of pregnancy. Participants will be randomized to each group in a 1:1 ratio based on duration of pregnancy at enrollment. The primary outcome is the proportion who have a complete abortion (no ongoing pregnancy) without procedural intervention or additional doses of medication as determined by negative HSPT between 28-42 days, ultrasound, or declining serum beta hCG by clinic protocols. Side effects, additional interventions, adverse events, acceptability, and quality of care will be assessed with daily surveys for the first 3 days, and thereafter weekly at 7, 14, 21, 28, and 35 days.

The primary outcome for this study is complete abortion, defined as successful expulsion of the intrauterine pregnancy without need for procedural intervention or additional doses of medication during the follow-up period as determined by negative HSPT between 28-42 days, ultrasound, or declining serum beta hCG by clinic protocols. The investigators will report abortion completion overall by study arm. Additionally, the investigators will evaluate and report on the non-inferiority of abortion completion following use of the misoprostol-only regimen as compared to the combined mifepristone and misoprostol regimen.

Participants will be determined to have had a complete abortion without need for procedural intervention or additional doses of medication, and the investigators will also report the number and proportion of complete abortions as defined more broadly by the MARE guidelines as successful expulsion of the intrauterine pregnancy without need for procedural intervention.

Secondary study endpoints include:

• change in serum beta hCG 7-14 days following use of the misoprostol-only regimen and in the mifepristone-misoprostol regimen

In more detail, secondary outcomes to be measured include declines in serum beta hCG between baseline and 7-14 days among a subset of participants to characterize patterns following use of the misoprostol-only regimen and the combined mifepristone-misoprostol regimen.

Inclusion criteria

• Pregnancy of < or = 77 days duration based on LMP or ultrasound
• Positive pregnancy test (self-report or in-clinic)
• Age: States without parental involvement laws : in-person patients ages 14 years and older; States with parental involvement or notification laws: 18 years or older
• Willing and able to give informed consent
• Willing to comply with study protocol
• Willing to record requested information in the study surveys
• English or Spanish speaking
• Has a text message, email, or phone call capable device for survey completion
• Understands and signs an Institutional Review Board (IRB) approved informed consent form prior to undergoing any study procedures or randomization

Exclusion criteria

• concurrent participation in any other interventional trial
• unwilling to comply with the study protocol and survey/visit schedule
• 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)
• diagnosis of porphyria
• known bleeding disorder or receiving anticoagulants
• pregnancy with an IUD in place
• diagnosis of pregnancy of unknown location (PUL), early pregnancy failure, incomplete or inevitable abortion (absent gestational sac and/or open cervical os)
• possibility of ectopic pregnancy
• known or suspected pelvic infection
• Have issues or concerns (in the judgement of the investigator) that may compromise the safety of the subject or confound the reliability of compliance and information acquired in this study.
• Have previously participated in the study
• Be a site staff member with delegated study responsibilities or a family member of, or have a close relationship with, a site staff member with delegated study responsibilities.