Persistent Pregnancy of Unknown LocationPhase 1/2PPULNCT01800162
RCT for Women With a Persisting Pregnancy of Unknown Location
A Phase 1/2 study testing Methotrexate, Uterine Evacuation and Expectant Management in people with Persistent Pregnancy of Unknown Location and Ectopic Pregnancy, run by University of Pennsylvania at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Persistent Pregnancy of Unknown Location, Ectopic Pregnancy
- What is being tested?
- Methotrexate, Uterine Evacuation and Expectant Management
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2013to Dec 2013
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female with a persisting pregnancy of unknown location:
- 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)
- 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.)
- Patient is hemodynamically stable, hemoglobin greater than 10 mg/dL,
- Greater than or 18 years of age
Who cannot join
- Hemodynamically unstable in need of acute treatment
- Most recent hCG greater than 5000 IU/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,
- Presence of clinical contraindications for treatment with methotrexate (ACOG guidelines, Appendix B),
- Prior medical or surgical management of this gestation.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Greenville Hospital System University Medical Center
Greenville, South Carolina, 29605
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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
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.
- Being tested
- Methotrexate, Uterine Evacuation, Expectant Management
- Medical subject headings
- Pregnancy, Ectopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
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 EvacuationProcedure or surgery
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.
Expectant ManagementOther
Pregnancy will be expectantly managed using serum hcg monitoring.
| Study group | Role | What they receive |
|---|---|---|
| Uterine evacuation, then MTX for some | Active comparator | 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. Receives: Drug: Methotrexate; Procedure: Uterine Evacuation |
| Empiric treatment with MTX for all | Active comparator | 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. Receives: Drug: Methotrexate |
| Expectant Management | Active comparator | Subjects will have their PPUL expectantly managed using serum hCG monitoring. Receives: Other: Expectant Management |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Outcome will be assessed within 6 weeks of randomization
Secondary outcomes (9)
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.
Measured: 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 group
- additional number of MTX injections
- additional surgical procedures
- uterine evacuation (or dilation and curettage)
- laparoscopy
- laparotomy
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionDec 2013
- Study completionDec 2013
Why it stopped: A new protocol was written to replace this protocol.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Persistent Pregnancy of Unknown LocationStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kurt T Barnhart, MD, MSCE, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01800162
- Sponsor's protocol ID
- 815013
- Acronym
- PPUL
- Status last verified
- Dec 2017
- First submitted
- 25 Feb 2013
- Last updated
- 29 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01800162
- Acronym / sponsor ID
- PPUL / 815013
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A new protocol was written to replace this protocol.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 27 Feb 2013 (estimated)
- Results
- Posted 15 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Uterine evacuation, then MTX for some | Active comparator | Drug: Methotrexate, Procedure: Uterine EvacuationSubjects 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. |
| Empiric treatment with MTX for all | Active comparator | Drug: MethotrexateSubjects 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. |
| Expectant Management | Active comparator | Other: Expectant ManagementSubjects will have their PPUL expectantly managed using serum hCG monitoring. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Female with a persisting pregnancy of unknown location:
- Patient is hemodynamically stable, hemoglobin greater than 10 mg/dL,
- Greater than or 18 years of age
Key exclusion criteria (7 listed)
- Hemodynamically unstable in need of acute treatment
- Most recent hCG greater than 5000 IU/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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateTwo 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. | Drug | Empiric treatment with MTX for all, Uterine evacuation, then MTX for some |
| Uterine EvacuationUterine 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. | Procedure or surgery | Uterine evacuation, then MTX for some |
| Expectant ManagementPregnancy will be expectantly managed using serum hcg monitoring. | Other | Expectant Management |
Primary outcome
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.
9 secondary outcomes
Number of Ruptured Ectopic Pregnancies in Each Group
Time frame: Outcome will be assess within 6 weeks of randomization
Quantification of Re-interventions Needed to Manage a Woman With a PPUL
Time frame: 6 weeks
Treatment Complications and Adverse Events
Time frame: 42 days after the last dose of study medication
Number of Procedures (Lab Tests, Ultrasounds)
Time frame: 6 weeks
Number of Visits
Time frame: 6 weeks
Time to Resolution
Time frame: 6 weeks
Patients' Preferences
Time frame: 6 weeks
Acceptability
Time frame: 6 weeks
Future Fertility
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kurt T Barnhart, MD, MSCE principal investigator
University of Pennsylvania
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Methotrexate, Uterine Evacuation and Expectant Management in people with Persistent Pregnancy of Unknown Location and Ectopic Pregnancy, run by University of Pennsylvania at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2017.