Persistent Pregnancy of Unknown Location, Ectopic Pregnancy
Conditions
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.
Interventions
DRUGMethotrexate
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.
PROCEDUREUterine 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.
OTHERExpectant Management
Pregnancy will be expectantly managed using serum hcg monitoring.
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Clinical Resolution for the 3 Different Management Arms for a Persisting PUL. | 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
| Measure | Time frame | Description |
|---|---|---|
| Quantification of Re-interventions Needed to Manage a Woman With a PPUL | 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 |
| Treatment Complications and Adverse Events | 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. |
| Number of Procedures (Lab Tests, Ultrasounds) | 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. |
| Number of Visits | 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. |
| Number of Ruptured Ectopic Pregnancies in Each Group | 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. |
| Patients' Preferences | 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. |
| Acceptability | 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. |
| Future Fertility | 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. |
| Time to Resolution | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment for the study has closed at both study sites, The University of Pennsylvania and Greenville.
Pre-assignment details
Subjects must be 18 years or older. Subject must have a positive pregnancy test but no signs of pregnancy visualized in the uterus or adnexa on ultrasound? Subject must have at least three serial hCG values over the past 4-14 days or two serial hCG values over the past 7-14 days. Subject must be hemodynamically stable with a hemoglobin \>10mg/dL.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
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. | 1 |
| 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.
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. | 0 |
| Expectant Management Subjects will have their PPUL expectantly managed using serum hCG monitoring.
Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Uterine Evacuation, Then MTX for Some | Empiric Treatment With MTX for All | Expectant Management | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Gestational Age | 14 weeks | — | 7 weeks | 21 weeks |
| Region of Enrollment Netherlands | 0 participants | — | 1 participants | 1 participants |
| Region of Enrollment United States | 1 participants | — | 0 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
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.
Time frame: Outcome will be assessed within 6 weeks of randomization
Population: 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
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.
Time frame: 6 weeks
Secondary
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.
Time frame: 6 weeks
Secondary
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.
Time frame: 6 weeks
Secondary
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.
Time frame: Outcome will be assess within 6 weeks of randomization
Secondary
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.
Time frame: 6 weeks
Secondary
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.
Time frame: 6 weeks
Secondary
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
Time frame: 6 weeks
Secondary
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.
Time frame: 6 weeks
Secondary
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.
Time frame: 42 days after the last dose of study medication