Clinical trial NCT02152696: Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Persistent Pregnancy of Unknown Location
Ectopic Pregnancy
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Augusta University
name: Penn State University
name: University of California, San Francisco
name: University of North Carolina
name: University of Oklahoma
name: University of Pennsylvania
First posted: 2014-06-02
Enrollment: 255
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy
timeFrame: 6 weeks from randomization
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: Denver Health
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University Of Illinois at Chicago
state: Illinois
city: Southfield
country: United States
facility: Wayne State University
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center - Women's Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Esther Eisenberg, MD MPH
role: STUDY_DIRECTOR
affiliation: University of Colorado, Denver
name: Nanette Santoro, MD
role: STUDY_CHAIR
affiliation: University of Pennsylvania
name: Kurt Barnhart, MD MSCE
role: PRINCIPAL_INVESTIGATOR
affiliation: Augusta University
name: Michael Diamond, MD
role: STUDY_DIRECTOR
affiliation: Penn State University
name: Richard Legro, MD
role: STUDY_DIRECTOR
affiliation: University of California, San Francisco
name: Marcelle Cedars, MD
role: STUDY_DIRECTOR
affiliation: University of North Carolina
name: Anne Steiner, MD MPH
role: STUDY_DIRECTOR
affiliation: University of Oklahoma
name: Karl Hansen, MD PhD
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Christos Coutifaris, MD PhD
role: STUDY_DIRECTOR
affiliation: Yale University
name: Heping Zhang, PhD
role: STUDY_DIRECTOR
References:
citation: 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.