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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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, 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.

Condition or disease	Intervention/treatment	Phase
Persistent Pregnancy of Unknown Location; Ectopic Pregnancy	Drug: Methotrexate; Procedure: Uterine Evacuation; Other: Expectant Management	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	2 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location -- a Randomized Clinical Trial of Women at Risk for an Ectopic Pregnancy
Study Start Date :	February 2013
Actual Primary Completion Date :	December 2013
Actual Study Completion Date :	December 2013

Arms and Interventions

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Arm	Intervention/treatment
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.
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: 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.

Outcome Measures

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Primary Outcome Measures :

1. Frequency of Clinical Resolution for the 3 Different Management Arms for a Persisting PUL. [ Time Frame: Outcome will be assessed within 6 weeks of randomization ]
   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.

Secondary Outcome Measures :

1. Number of Ruptured Ectopic Pregnancies in Each Group [ Time Frame: Outcome will be assess within 6 weeks of randomization ]
   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.
2. Quantification of Re-interventions Needed to Manage a Woman With a PPUL [ Time Frame: 6 weeks ]

   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
3. Treatment Complications and Adverse Events [ Time Frame: 42 days after the last dose of study medication ]
   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.
4. Number of Procedures (Lab Tests, Ultrasounds) [ Time Frame: 6 weeks ]
   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.
5. Number of Visits [ Time Frame: 6 weeks ]
   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. Time to Resolution [ Time Frame: 6 weeks ]
   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.
7. Patients' Preferences [ Time Frame: 6 weeks ]
   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.
8. Acceptability [ Time Frame: 6 weeks ]
   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.
9. Future Fertility [ Time Frame: 6 weeks ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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

Sponsors and Collaborators

University of Pennsylvania

Investigators

Principal Investigator:	Kurt T Barnhart, MD, MSCE	University of Pennsylvania

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT01800162 History of Changes
Other Study ID Numbers:	815013
First Posted:	February 27, 2013
Results First Posted:	May 15, 2017
Last Update Posted:	December 29, 2017
Last Verified:	December 2017

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Cardiac Complexes, Premature; Pregnancy, Ectopic; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pregnancy Complications; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs	Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors