Anembryonic Pregnancy, Missed Abortion, Non-Viable Pregnancy
Conditions
Keywords
Medical management of miscarriage
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.
Interventions
DRUGUlipristal Acetate Tablets
90mg (three 30mg tablets) administered orally once
DRUGMisoprostol Pill
800mcg (four 200mcg pills) administered vaginally once 6-18 hours following ulipristal acetate
Sponsors
North Carolina Translational and Clinical Sciences Institute
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Adherent to Study Protocol | From admission until day 3 follow up, +/- 1 day | 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. |
| Percentage of Participants Retained in Study Protocol | From admission until day 30 follow up, +/- 7 days | 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 |
| Percentage of Participants Recruited to Study Protocol | Baseline | Measured as number of participants enrolled in study divided by number of patients screened for participation in study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Acceptability of Study Intervention | From admission until day 30 follow up, +/- 7 days | 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. |
| Number of Participants With Treatment-Related Adverse Events | From admission until day 30 follow up, +/- 7 days | 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. |
| Number of Participants With Resolution of Early Pregnancy Loss Following Study Intervention | From admission until day 3 follow up, +/- 1 day | Absence of gestational sac on transvaginal ultrasound examination on day 3 follow up |
| Number of Participants With Treatment-Related Side Effects | From admission until day 30 follow up, +/- 7 days | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Needing Additional Medication for Resolution of Early Pregnancy Loss | From admission until day 30 follow up, +/- 7 days | Participant reported need for additional dose of misoprostol for resolution of early pregnancy loss. |
| Number of Participants Needing Surgical Management for Resolution of Early Pregnancy Loss | From admission until day 30 follow up, +/- 7 days | Participant reported need for vacuum aspiration for resolution of early pregnancy loss. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ulipristal Acetate (UPA) 90 mg Participants receive ulipristal acetate 90 mg PO followed by self-administration of misoprostol 800 mcg vaginally 6 to 18 hours following ulipristal acetate administration.
Ulipristal Acetate Tablets: 90 mg (three 30 mg tablets) administered orally once
Misoprostol Pill: 800 mcg (four 200 mcg pills) administered vaginally once 6-18 hours following ulipristal acetate | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Ulipristal Acetate (UPA) 90 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 34 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 |
Outcome results
Primary
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.
Time frame: From admission until day 3 follow up, +/- 1 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ulipristal Acetate (UPA) 90 mg | Percentage of Participants Adherent to Study Protocol | 100 percentage of participants |
Primary
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
Time frame: Baseline
Population: The number of potential participants screened for study eligibility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ulipristal Acetate (UPA) 90 mg | Percentage of Participants Recruited to Study Protocol | 37.5 percentage of participants |
Primary
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
Time frame: From admission until day 30 follow up, +/- 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ulipristal Acetate (UPA) 90 mg | Percentage of Participants Retained in Study Protocol | 100 percentage of participants |
Secondary
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.
Time frame: From admission until day 30 follow up, +/- 7 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ulipristal Acetate (UPA) 90 mg | Median Acceptability of Study Intervention | Would you use these medications again if you had another miscarriage? | 3 score on a scale |
| Ulipristal Acetate (UPA) 90 mg | Median Acceptability of Study Intervention | Would you recommend these medications to a friend with a miscarriage? | 4 score on a scale |
| Ulipristal Acetate (UPA) 90 mg | Median Acceptability of Study Intervention | If possible to take Ulipristal Acetate (UPA) at home, would you be more or less likely to use again? | 4 score on a scale |
| Ulipristal Acetate (UPA) 90 mg | Median Acceptability of Study Intervention | If possible to take UPA at a different time, would you be more or less likely to use again? | 3 score on a scale |
Secondary
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
Time frame: From admission until day 3 follow up, +/- 1 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Resolution of Early Pregnancy Loss Following Study Intervention | 3 Participants |
Secondary
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.
Time frame: From admission until day 30 follow up, +/- 7 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Adverse Events | Bleeding requiring hospitalization and/or blood transfusion | 1 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Adverse Events | Pelvic infection requiring hospitalization and/or antibiotics | 0 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Adverse Events | Other | 0 Participants |
Secondary
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.
Time frame: From admission until day 30 follow up, +/- 7 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Side Effects | Severe cramping | 1 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Side Effects | Fatigue | 2 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Side Effects | Headache | 0 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Side Effects | Dizziness | 2 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Side Effects | Chills | 1 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Side Effects | Nausea | 1 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Side Effects | Diarrhea | 0 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Side Effects | Vomiting | 0 Participants |
| Ulipristal Acetate (UPA) 90 mg | Number of Participants With Treatment-Related Side Effects | Fever | 0 Participants |
Other Pre-specified
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.
Time frame: From admission until day 30 follow up, +/- 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ulipristal Acetate (UPA) 90 mg | Number of Participants Needing Additional Medication for Resolution of Early Pregnancy Loss | 0 Participants |
Other Pre-specified
Number of Participants Needing Surgical Management for Resolution of Early Pregnancy Loss
Participant reported need for vacuum aspiration for resolution of early pregnancy loss.
Time frame: From admission until day 30 follow up, +/- 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ulipristal Acetate (UPA) 90 mg | Number of Participants Needing Surgical Management for Resolution of Early Pregnancy Loss | 0 Participants |