Ulipristal Acetate for Use in Early Pregnancy Loss

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Missed Abortion, Anembryonic Pregnancy, Non-Viable Pregnancy

Intervention / Treatment
-----------------
* Drug: Ulipristal Acetate Tablets
* Drug: Misoprostol Pill


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UPA 90mg<br>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<br>* 90mg (three 30mg tablets) administered orally once<br>* Other names: Ella;Drug: Misoprostol Pill<br>* 800mcg (four 200mcg pills) administered vaginally once 6-18 hours following ulipristal acetate<br>* 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 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 | 
| 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 | 

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Medical management of miscarriage