RCT 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, and 3) Expectant management. Randomization will be 2:2:1 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. Secondary outcome measures: re-interventions, treatment complications, health-related quality of life, financial costs, future fertility, and patient's preferences.

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

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 women with a positive pregnancy test but no definitive signs of pregnancy in the uterus or adnexa on ultrasound imaging (Ultrasound must be performed within 7 days prior to randomization) Persistence of hCG is defined as 3 serial hCG values over 4-14 days or 2 serial hCG values over 7-14 days, showing less than 30% rise, or less than 30% fall between the first and last value. (This abnormal pattern of serial hCG confirms that the gestation is nonviable.) Patient is hemodynamically stable, hemoglobin greater than 10 mg/dL, Greater than or 18 years of age Exclusion Criteria: Hemodynamically unstable in need of acute treatment Most recent hCG greater than 5000 IU/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, Presence of clinical contraindications for treatment with methotrexate (ACOG guidelines, Appendix B), Prior medical or surgical management of this gestation.

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: Uterine evacuation, then 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>|
| 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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Clinical Resolution for the 3 Different Management Arms for a Persisting PUL. | Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome. | Outcome will be assessed within 6 weeks of randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Ruptured Ectopic Pregnancies in Each Group | Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome. | Outcome will be assess within 6 weeks of randomization | 
| Quantification of Re-interventions Needed to Manage a Woman With a PPUL | Outcomes include: number of interventions beyond that of intended initial strategy in each group additional number of MTX injections additional surgical procedures uterine evacuation (or dilation and curettage) laparoscopy laparotomy | 6 weeks | 
| Treatment Complications and Adverse Events | Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome. | 42 days after the last dose of study medication | 
| Number of Procedures (Lab Tests, Ultrasounds) | Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome. | 6 weeks | 
| Number of Visits | Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome. | 6 weeks | 
| Time to Resolution | Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome. | 6 weeks | 
| Patients' Preferences | Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome. | 6 weeks | 
| Acceptability | Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome. | 6 weeks | 
| Future Fertility | Data was not analyzed as the study was closed early. Data is not anticipated to be analyzed for this study. Patients were not followed for outcome. | 6 weeks |