Persistent Pregnancy of Unknown LocationPhase 3ACTorNOTNCT02152696
Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location
A Phase 3 study testing Methotrexate, Uterine Evacuation and Expectant Management in people with Persistent Pregnancy of Unknown Location and Ectopic Pregnancy, run by Yale University at 17 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
- 255 participants
- Where
- 17 sitesUnited States
- Study dates
- 25 Jul 2014to 19 Aug 2019
- Phase
- Phase 3
- 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 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
Who cannot join
- 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
Show all 9Show fewer
- Presence of clinical contraindications for treatment with MTX
- Prior medical or surgical management of this gestation
- Subject unwilling to accept a blood transfusion
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Augusta University
Augusta, Georgia, 30912
University of North Carolina
Chapel Hill, North Carolina, 27599
Carolinas Medical Center - Women's Institute
Charlotte, North Carolina, 28204
Northwestern University
Chicago, Illinois, 60611
University Of Illinois at Chicago
Chicago, Illinois, 60612
Denver Health
Denver, Colorado, 80204
Duke University
Durham, North Carolina, 27708
Greenville Health System
Greenville, South Carolina, 29605
Yale University
New Haven, Connecticut, 06520
University of Oklahoma
Oklahoma City, Oklahoma, 73104
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Rochester
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84132
University of California San Francisco
San Francisco, California, 94115
Wayne State University
Southfield, Michigan, 48034
Washington University
St Louis, Missouri, 63108
University of South Florida
Tampa, Florida, 33606
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: Active Treatment Versus No Treatment
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.
- 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 |
|---|---|---|
| Expectant Management | Active comparator | Subjects will have their PPUL expectantly managed using serum hCG monitoring. Receives: Other: Expectant Management |
| Uterine evacuation with 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2014 (estimated)
- Study start25 Jul 2014
- Primary completionAug 2019
- Study completion19 Aug 2019
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Persistent Pregnancy of Unknown LocationStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 255 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Sponsor
- Investigators
- Esther Eisenberg, MD MPH, Study director, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Nanette Santoro, MD, Study chair, University of Colorado, DenverKurt Barnhart, MD MSCE, Principal investigator, University of PennsylvaniaMichael Diamond, MD, Study director, Augusta UniversityRichard Legro, MD, Study director, Penn State UniversityMarcelle Cedars, MD, Study director, University of California, San FranciscoAnne Steiner, MD MPH, Study director, University of North CarolinaKarl Hansen, MD PhD, Study director, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02152696
- Sponsor's protocol ID
- 2000023590
- Other IDs
- 2U10HD055925-06
- Acronym
- ACTorNOT
- Status last verified
- Nov 2020
- First submitted
- 28 May 2014
- Last updated
- 8 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: IPD will be shared with other researchers through the NICHD DASH system. It will be available 6 months after publication of the primary results.
Publications
Barnhart KT, Hansen KR, Stephenson MD, Usadi R, Steiner AZ, Cedars MI, Jungheim ES, Hoeger KM, Krawetz SA, Mills B, Alston M, Coutifaris C, Senapati S, Sonalkar S, Diamond MP, Wild RA, Rosen M, Sammel MD, Santoro N, Eisenberg E, Huang H, Zhang H; Reproductive Medicine Network. Effect of an Active vs Expectant Management Strategy on Successful Resolution of Pregnancy Among Patients With a Persisting Pregnancy of Unknown Location: The ACT or NOT Randomized Clinical Trial. JAMA. 2021 Aug 3;326(5):390-400. doi: 10.1001/jama.2021.10767.
PubMed 34342619
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. 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: Active Treatment Versus No Treatment
- ClinicalTrials.gov ID
- NCT02152696
- Acronym / sponsor ID
- ACTorNOT / 2000023590
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 255 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- 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
- Study start
- 25 Jul 2014 (actual)
- Primary completion
- Aug 2019 (actual)
- Study completion
- 19 Aug 2019 (actual)
- First posted
- 2 Jun 2014 (estimated)
- Results
- Posted 26 Oct 2020
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Expectant Management | Active comparator | Other: Expectant ManagementSubjects will have their PPUL expectantly managed using serum hCG monitoring. |
| Uterine evacuation with 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. |
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:
- 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
Key exclusion criteria (9 listed)
- 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
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 with 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 with MTX for some |
| Expectant ManagementPregnancy will be expectantly managed using serum hcg monitoring | Other | Expectant Management |
Primary outcome
Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34342619Barnhart KT, Hansen KR, Stephenson MD, Usadi R, Steiner AZ, Cedars MI, Jungheim ES, Hoeger KM, Krawetz SA, Mills B, Alston M, Coutifaris C, Senapati S, Sonalkar S, Diamond MP, Wild RA, Rosen M, Sammel MD, Santoro N, Eisenberg E, Huang H, Zhang H; Reproductive Medicine Network. Effect of an Active vs Expectant Management Strategy on Successful Resolution of Pregnancy Among Patients With a Persisting Pregnancy of Unknown Location: The ACT or NOT Randomized Clinical Trial. JAMA. 2021 Aug 3;326(5):390-400. doi: 10.1001/jama.2021.10767.
- Individual participant dataSharing planned: Yes. IPD will be shared with other researchers through the NICHD DASH system. It will be available 6 months after publication of the primary results.
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.
Esther Eisenberg, MD MPH study director
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Nanette Santoro, MD study chair
University of Colorado, Denver
Kurt Barnhart, MD MSCE principal investigator
University of Pennsylvania
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methotrexate, Uterine Evacuation and Expectant Management in people with Persistent Pregnancy of Unknown Location and Ectopic Pregnancy, run by Yale University at 17 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 9 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: finished, as of the sponsor's last update on 8 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 26 Oct 2020). 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?
Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy (time frame: 6 weeks from randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02152696, which also lists 1 linked publication.
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 8 Dec 2020.