RCT for Women With a Persisting Pregnancy of Unknown Location (PPUL)

Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location -- a Randomized Clinical Trial of Women at Risk for an Ectopic Pregnancy

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.

Study Overview

• Status: Terminated
• Conditions: Ectopic Pregnancy; Persistent Pregnancy of Unknown Location
• Intervention / Treatment: Drug: Methotrexate; Procedure: Uterine Evacuation; Other: Expectant Management

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female with a persisting pregnancy of unknown location:

   1. 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)
   2. 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.)
2. Patient is hemodynamically stable, hemoglobin greater than 10 mg/dL,
3. Greater than or 18 years of age

Exclusion Criteria:

1. Hemodynamically unstable in need of acute treatment
2. Most recent hCG greater than 5000 IU/mL
3. Patient obtaining care in relation to a recently completed pregnancy (delivery, spontaneous or elective abortion),
4. Diagnosis of gestational trophoblastic disease,
5. Subject unwilling or unable to comply with study procedures,
6. Presence of clinical contraindications for treatment with methotrexate (ACOG guidelines, Appendix B),
7. Prior medical or surgical management of this gestation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Expectant Management; Subjects will have their PPUL expectantly managed using serum hCG monitoring.	Other: Expectant Management; Pregnancy will be expectantly managed using serum hcg monitoring.
Active Comparator: Empiric treatment with MTX for all; 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; 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.
Active Comparator: Uterine evacuation, then MTX for some; 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; 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.; Procedure: Uterine Evacuation; 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.

What is the study measuring?

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 groupadditional number of MTX injectionsadditional 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

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: February 25, 2013
• First Submitted That Met QC Criteria: February 25, 2013
• First Posted (Estimate): February 27, 2013

Study Record Updates

• Last Update Posted (Actual): December 29, 2017
• Last Update Submitted That Met QC Criteria: December 5, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pregnancy Complications; Pregnancy, Ectopic; Cardiac Complexes, Premature; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: 815013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No