Ulipristal Acetate for Use in Early Pregnancy Loss

Ulipristal Acetate for Use in Early Pregnancy Loss: A Phase 2 Pilot Feasibility Study

The investigators will study the feasibility of using 90mg ulipristal acetate, a selective progesterone receptor agonist, as an adjunct to 800mcg vaginal misoprostol for the medical management of early pregnancy loss. Patients will be followed to assess effective treatment of early pregnancy loss, additional interventions needed, side effects, adverse events and patient acceptability.

Study Overview

• Status: Completed
• Conditions: Non-Viable Pregnancy; Missed Abortion; Anembryonic Pregnancy
• Intervention / Treatment: Drug: Ulipristal Acetate Tablets; Drug: Misoprostol Pill

Detailed Description

Study Background: Early pregnancy loss affects approximately 10% of women throughout their reproductive lives and many women desire medical management of early pregnancy loss. Data from two large randomized controlled trials suggests that pretreatment with mifepristone 200mg, a selective progesterone receptor modulator, prior to administration of misoprostol 800mcg increases effectiveness of medical management of early pregnancy loss and decreases the need for subsequent surgical management. Ulipristal acetate (UPA) is another selective progesterone receptor modulator that may allow for similar priming of the cervix and sensitization of the myometrium to the prostaglandins to improve effectiveness of misoprostol in medical management of early pregnancy loss. Ulipristal acetate is available as a prescription medication through commercial pharmacies. Thus, utilizing UPA plus misoprostol for early pregnancy loss may improve access to patients.

Study Objectives:

Primary Objective:

- To assess if 90mg ulipristal acetate as an adjunct to 800mcg vaginal misoprostol is a feasible method for medical management of early pregnancy loss.

Secondary Objectives:

• To evaluate if participants taking ulipristal acetate plus misoprostol achieve complete resolution of early pregnancy loss.
• To investigate if patients using ulipristal acetate plus misoprostol have side effects or adverse events when used for early pregnancy loss.
• To identify if patients find ulipristal acetate and misoprostol an acceptable treatment for early pregnancy loss.

Study Population: Participants eligible for the study include women over age 18 presenting with a non-viable pregnancy between 5- and 12-weeks gestation or an anembryonic gestation and desiring medical management.

Study Location: All study activities will take place at University of North Carolina-Chapel Hill (UNC). Participants will be recruited from OBGYN clinics following diagnosis of early pregnancy loss on viability scan. All follow up study activities will take place at UNC Chapel Hill Family Planning Clinic.

Study Intervention: Ulipristal acetate is a selective progesterone receptor modulator that is currently FDA approved for the use of emergency contraception. Three 30mg tablets will be administered orally for a total dose of 90mg. Participants will be instructed to self-administer 800mcg of misoprostol 6 to 18 hours after receiving ulipristal acetate as per the standard of care for early pregnancy loss management. Participants will be followed for resolution of their early pregnancy loss.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina, Chapel Hill - Same Day OBGYN Clinic
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina, Chapel Hill - Vilcom Center
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina, Chapel Hill - Weaver Crossing
    • Hillsborough, North Carolina, United States, 27278
      • University of North Carolina, Chapel Hill - Hillsborough Medical Office Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female, age 18 years or older
• English- or Spanish-speaking
• Ultrasound examination showing a non-viable intrauterine pregnancy between 5- and 12-weeks' gestation or anembryonic gestation
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Provision of signed and dated informed consent form

Exclusion Criteria:

• Desire for non-medical management of early pregnancy loss (either expectant management or surgical management)
• Hemodynamically unstable
• Evidence of incomplete or inevitable abortion (due to high efficacy of misoprostol alone)
• Contraindication or allergy to ulipristal acetate or misoprostol (glaucoma, mitral stenosis, sickle cell anemia, chronic glucocorticoid use)
• Evidence of a viable intrauterine pregnancy, ectopic pregnancy, or pregnancy with intrauterine device in place
• Evidence of pelvic infection
• Hemoglobin <9.5g/dL
• Known cardiovascular disease (arrhythmia, cardiac failure, valvular disease, angina)
• Known clotting or bleeding disorder, or on anticoagulation therapy
• Use of the following medications that may influence metabolization of the study medications: barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's Wort, topiramate
• Use of CYP3A4 inhibitors within five elimination half-lives of ulipristal acetate or other strong CYP3A4 inhibitors
• Chronic adrenal failure (risk of acute renal insufficiency)
• Concurrent long-term corticosteroid therapy (risk of acute renal insufficiency)
• Any history of underlying liver disorder, including hepatitis
• Elevation of any or all liver enzymes (alanine aminotransferase, aspartate aminotransferase, total bilirubin) above the upper limit of normal (ULN) at baseline testing prior to enrollment
• A family history of hepatitis or currently living with a person who has been given a diagnosis of hepatitis
• A history of or currently working as a sex worker
• A history of or currently using intravenous (IV) drugs
• A self-reported history of alcohol dependency or abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UPA 90mg; Participants receive ulipristal acetate 90mg PO followed by self-administration of misoprostol 800mcg vaginally 6 to 18 hours following ulipristal acetate administration.	Drug: Ulipristal Acetate Tablets; 90mg (three 30mg tablets) administered orally once; Other Names: Ella; Drug: Misoprostol Pill; 800mcg (four 200mcg pills) administered vaginally once 6-18 hours following ulipristal acetate; Other Names: Cytotec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Recruited to Study Protocol	Measured as number of participants enrolled in study divided by number of patients screened for participation in study	Baseline
Percentage of Participants Retained in Study Protocol	Measured as number of participants attending all required study visits (day 0, day 3, day 8, and day 30) divided by number of participants enrolled in study	From admission until day 30 follow up, +/- 7 days
Percentage of Participants Adherent to Study Protocol	Measured as number of participants self reporting adherence to study intervention of ulipristal acetate followed by misoprostol taken 6-18 hours later divided by number of participants enrolled in study.	From admission until day 3 follow up, +/- 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Resolution of Early Pregnancy Loss Following Study Intervention	Absence of gestational sac on transvaginal ultrasound examination on day 3 follow up	From admission until day 3 follow up, +/- 1 day
Number of Participants With Treatment-Related Side Effects	Participant reported side effects based on pre-specified list of common side effects (fatigue, headache, dizziness, chills, nausea, diarrhea, vomiting, severe cramping, and fever) that may occur with medication management of early pregnancy loss.	From admission until day 30 follow up, +/- 7 days
Number of Participants With Treatment-Related Adverse Events	Participant reported adverse events based on pre-specified list (bleeding requiring hospitalization and/or blood transfusion, pelvic infection requiring hospitalization and/or antibiotics) that may occur with medication management of early pregnancy loss.	From admission until day 30 follow up, +/- 7 days
Median Acceptability of Study Intervention	Participant reported ordinal data based on 4 Likert scale questions about acceptability of study intervention with scores ranging from 1-5 (1=Very Unlikely, 2=More Unlikely, 3=Neutral, 4=More Likely, 5=Very Likely). Higher scores indicated more acceptable treatment.	From admission until day 30 follow up, +/- 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Needing Additional Medication for Resolution of Early Pregnancy Loss	Participant reported need for additional dose of misoprostol for resolution of early pregnancy loss.	From admission until day 30 follow up, +/- 7 days
Number of Participants Needing Surgical Management for Resolution of Early Pregnancy Loss	Participant reported need for vacuum aspiration for resolution of early pregnancy loss.	From admission until day 30 follow up, +/- 7 days

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: North Carolina Translational and Clinical Sciences Institute
• Investigators: Principal Investigator: Jill M Hagey, MD, MPH, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2022
• Primary Completion (Actual): January 3, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Medical management of miscarriage
• Additional Relevant MeSH Terms: Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Abortion, Spontaneous; Abortion, Missed; Physiological Effects of Drugs; Gastrointestinal Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol; Ulipristal acetate
• Other Study ID Numbers: 21-2315; C21-1493 (Other Identifier: UNC Chapel Hill Clinical Research Management)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: Study protocol, statistical analysis plan and informed consent form will be shared beginning 9 to 36 months following publication of results.
• IPD Sharing Access Criteria: Following approval from an appropriate review board as described above and execution of a data use/sharing agreement with UNC-Chapel Hill.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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