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 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.
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
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Augusta University
Penn State University
University of California, San Francisco
University of North Carolina
University of Oklahoma
University of Pennsylvania
Yale University
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy | 6 weeks from randomization | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Expectant Management Subjects will have their PPUL expectantly managed using serum hCG monitoring.
Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring | 86 |
| Uterine Evacuation With 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. | 87 |
| 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. | 82 |
| Total | 255 |
Baseline characteristics
| Characteristic | Total | Expectant Management | Uterine Evacuation With MTX for Some | Empiric Treatment With MTX for All |
|---|---|---|---|---|
| Age, Continuous | 31.6 years STANDARD_DEVIATION 5.7 | 32.1 years STANDARD_DEVIATION 5.6 | 31.2 years STANDARD_DEVIATION 5.9 | 31.5 years STANDARD_DEVIATION 5.7 |
| Estimated gestational age - week | 6.7 weeks STANDARD_DEVIATION 1.9 | 6.4 weeks STANDARD_DEVIATION 1.8 | 6.9 weeks STANDARD_DEVIATION 1.9 | 6.7 weeks STANDARD_DEVIATION 2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 3 Participants | 8 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 229 Participants | 80 Participants | 75 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 3 Participants | 4 Participants | 2 Participants |
| First hCG value at screening (mIU/ml) | 618.3 mIU/ml STANDARD_DEVIATION 694.2 | 661.2 mIU/ml STANDARD_DEVIATION 688.6 | 561.9 mIU/ml STANDARD_DEVIATION 702.5 | 633.3 mIU/ml STANDARD_DEVIATION 695.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 3 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 102 Participants | 37 Participants | 33 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 5 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) White | 120 Participants | 41 Participants | 40 Participants | 39 Participants |
| Region of Enrollment United States | 255 Participants | 86 Participants | 87 Participants | 82 Participants |
| Sex: Female, Male Female | 255 Participants | 86 Participants | 87 Participants | 82 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 | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 86 | 0 / 87 | 0 / 82 |
| other Total, other adverse events | 44 / 86 | 53 / 87 | 46 / 82 |
| serious Total, serious adverse events | 2 / 86 | 2 / 87 | 0 / 82 |
Outcome results
Primary
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.
Time frame: 6 weeks from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Expectant Management | Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy | 31 Participants |
| Uterine Evacuation With MTX for Some | Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy | 42 Participants |
| Empiric Treatment With MTX for All | Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy | 45 Participants |