PPUL: RCT for Women With a Persisting Pregnancy of Unknown Location

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01800162
• Collaborator: (none)
• Enrollment: 2
• Locations: 2
• Arms: 3
• Duration (Months): 10
• Patient Per Site: 1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

• Study Type: Interventional
• 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: Feb 1, 2013
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

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

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Female with a persisting pregnancy of unknown location:

2. 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)

3. 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.)

4. Patient is hemodynamically stable, hemoglobin greater than 10 mg/dL,

5. 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

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01800162
• Other Study ID Numbers: 815013
• First Posted: Feb 27, 2013
• Last Update Posted: Dec 29, 2017
• Last Verified: Dec 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Pregnancy, Ectopic; Cardiac Complexes, Premature; Methotrexate

Study Results

Participant Flow

Recruitment Details	Recruitment for the study has closed at both study sites, The University of Pennsylvania and Greenville.
Pre-assignment Detail	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.

Arm/Group Title	Uterine Evacuation, Then MTX for Some	Empiric Treatment With MTX for All	Expectant Management
Arm/Group Description	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.	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.	Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring.
Period Title: Overall Study
STARTED	1	0	1
COMPLETED	1	0	1
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Uterine Evacuation, Then MTX for Some	Empiric Treatment With MTX for All	Expectant Management	Total
Arm/Group Description	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.	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.	Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring.	Total of all reporting groups
Overall Participants	1	0	1	2
Age (Count of Participants)
<=18 years	0 0%	0 NaN	0 0%	0 0%
Between 18 and 65 years	1 100%	0 NaN	1 100%	2 100%
>=65 years	0 0%	0 NaN	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%	0 NaN	1 100%	2 100%
Male	0 0%	0 NaN	0 0%	0 0%
Region of Enrollment (participants) [Number]
Netherlands	0 0%	1 Infinity	1 100%
United States	1 100%	0 NaN	1 100%
Gestational Age (weeks) [Number]
Number [weeks]	14	7	21

Outcome Measures

1. Primary Outcome

Title	Frequency of Clinical Resolution for the 3 Different Management Arms for a Persisting PUL.
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Uterine Evacuation	Expectant Management
Arm/Group Description	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.	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.
Measure Participants	0	0

2. Secondary Outcome

Title	Number of Ruptured Ectopic Pregnancies in Each Group
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uterine Evacuation	Expectant Management
Arm/Group Description	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.	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.
Measure Participants	0	0

3. Secondary Outcome

Title	Quantification of Re-interventions Needed to Manage a Woman With a PPUL
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uterine Evacuation	Expectant Management
Arm/Group Description	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.	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.
Measure Participants	0	0

4. Secondary Outcome

Title	Treatment Complications and Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uterine Evacuation	Expectant Management
Arm/Group Description	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.	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.
Measure Participants	0	0

5. Secondary Outcome

Title	Number of Procedures (Lab Tests, Ultrasounds)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uterine Evacuation	Expectant Management
Arm/Group Description	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.	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.
Measure Participants	0	0

6. Secondary Outcome

Title	Number of Visits
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uterine Evacuation	Expectant Management
Arm/Group Description	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.	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.
Measure Participants	0	0

7. Secondary Outcome

Title	Time to Resolution
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uterine Evacuation	Expectant Management
Arm/Group Description	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.	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.
Measure Participants	0	0

8. Secondary Outcome

Title	Patients' Preferences
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uterine Evacuation	Expectant Management
Arm/Group Description	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.	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.
Measure Participants	0	0

9. Secondary Outcome

Title	Acceptability
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uterine Evacuation	Expectant Management
Arm/Group Description	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.	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.
Measure Participants	0	0

10. Secondary Outcome

Title	Future Fertility
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Uterine Evacuation, Then MTX for Some	Expectant Management
Arm/Group Description	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.	Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Uterine Evacuation		Expectant Management
Arm/Group Description	No AE to Report		No AE to Report
All Cause Mortality
	Uterine Evacuation		Expectant Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Serious Adverse Events
	Uterine Evacuation		Expectant Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Uterine Evacuation		Expectant Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.