Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location

Phase 3

Completed

Interventions: Other: Expectant Management
Drug: Methotrexate
Procedure: Uterine Evacuation

Brief Summary: This is a randomized controlled trial to compare three currently available management strategies for women with a persisting pregnancy of unknown location (PPUL), which makes them at-risk for ectopic pregnancy. We will recruit hemodynamically stable women with a confirmed PPUL to be randomized to one of three strategies: 1) Uterine evacuation followed by methotrexate (MTX) for some (those that have evidence of a non visualized ectopic pregnancy) 2) Empiric treatment with MTX for all 3) Expectant management. Randomization will be 1:1:1 into these three arms. After randomization, they will be followed and treated clinically as is indicated by the progression of their condition. Primary outcome measures: uneventful decline of hCG to 5 IU/mL.

Recruitment & Eligibility

Inclusion Criteria

Female with a persisting pregnancy of unknown location:
A pregnancy of unknown location is defined as a pregnancy in a woman with a positive pregnancy test but no definitive signs of pregnancy in the uterus or adnexa on ultrasound imaging. A definitive sign of gestation includes ultrasound visualization of a gestational sac with a yolk sac (with or without an embryo) in the uterus or in the adnexa. Ultrasound must be performed within 7 days prior to randomization.
Persistence of hCG is defined as at least 2 serial hCG values (over 2-14 days), showing < 15% rise per day, or < 50% fall between the first and last value.
Patient is hemodynamically stable, hemoglobin >10 mg/dL
Greater than or 18 years of age

Exclusion Criteria

Hemodynamically unstable in need of acute treatment
Most recent hCG > 5000 mIU/mL
Patient obtaining care in relation to a recently completed pregnancy (delivery, spontaneous or elective abortion)
Diagnosis of gestational trophoblastic disease
Subject unwilling or unable to comply with study procedures
Known hypersensitivity to MTX
Presence of clinical contraindications for treatment with MTX
Prior medical or surgical management of this gestation
Subject unwilling to accept a blood transfusion

Arm && Interventions

Group	Intervention	Description
Expectant Management	Expectant Management	Subjects will have their PPUL expectantly managed using serum hCG monitoring.
Uterine evacuation with MTX for some	Uterine Evacuation	Subjects will undergo a uterine evacuation. If hCG levels do not sufficiently decrease after the uterine evacuation, the subject will be treated with methotrexate. If hCG levels do sufficiently decrease after the uterine evacuation, no further treatment is required.
Uterine evacuation with MTX for some	Methotrexate	Subjects will undergo a uterine evacuation. If hCG levels do not sufficiently decrease after the uterine evacuation, the subject will be treated with methotrexate. If hCG levels do sufficiently decrease after the uterine evacuation, no further treatment is required.
Empiric treatment with MTX for all	Methotrexate	Subjects will be treated with methotrexate, receiving one dose on day 0 and a subsequent dose on day 4. Additional doses will be administered as needed based on hCG levels.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy	6 weeks from randomization	The primary outcome measure in each of each 3 treatment arm is the uneventful clinical resolution of a PPUL without change in treatment from the initial management strategy.

Secondary Outcome Measures

Name	Time	Method

Locations (17): Wayne State University
🇺🇸
Southfield, Michigan, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
University of South Florida
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Tampa, Florida, United States
Duke University
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Durham, North Carolina, United States
Augusta University
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Augusta, Georgia, United States
University of Rochester
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Rochester, New York, United States
Carolinas Medical Center - Women's Institute
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Charlotte, North Carolina, United States
University of Pennsylvania
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Philadelphia, Pennsylvania, United States
Denver Health
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Denver, Colorado, United States
University of California San Francisco
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San Francisco, California, United States
Northwestern University
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Chicago, Illinois, United States
University Of Illinois at Chicago
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Chicago, Illinois, United States
Washington University
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Saint Louis, Missouri, United States
University of North Carolina
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Chapel Hill, North Carolina, United States
Greenville Health System
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Greenville, South Carolina, United States
University of Utah
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Salt Lake City, Utah, United States
University of Oklahoma
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Oklahoma City, Oklahoma, United States