Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location

Study Overview
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Brief Summary
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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.

Official Title
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Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location - a Randomized Clinical Trial of Women at Risk for an Ectopic Pregnancy: Active Treatment Versus No Treatment

Conditions
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Persistent Pregnancy of Unknown Location, Ectopic Pregnancy

Intervention / Treatment
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* Drug: Methotrexate
* Procedure: Uterine Evacuation
* Other: Expectant Management


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Expectant Management<br>Subjects will have their PPUL expectantly managed using serum hCG monitoring. | Other: Expectant Management<br>* Pregnancy will be expectantly managed using serum hcg monitoring<br>|
| Active Comparator: Uterine evacuation with MTX for some<br>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. | Drug: Methotrexate<br>* Two Dose Protocol: The patient will receive the first dose of MTX 50mg/m2 on treatment day 0. She will receive a second dose of MTX 50mg/m2 on treatment day 4 and a serum hCG level will be drawn. Subsequent doses of MTX will be administered based on hCG levels.<br>Procedure: Uterine Evacuation<br>* Uterine evacuation or dilation and curettage. At the clinician's discretion, this can be performed using local anesthesia, sedation or general anesthesia and can use a manual or electrical evacuation.<br>|
| Active Comparator: Empiric treatment with MTX for all<br>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. | Drug: Methotrexate<br>* Two Dose Protocol: The patient will receive the first dose of MTX 50mg/m2 on treatment day 0. She will receive a second dose of MTX 50mg/m2 on treatment day 4 and a serum hCG level will be drawn. Subsequent doses of MTX will be administered based on hCG levels.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy | 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. | 6 weeks from randomization |