Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location

NCT02152696 | Completed Phase 3 Results DMC

• 2 other identifiers: 20000235902U10HD055925-06
• Study Type: interventional
• Target: 255
• Locations: 1 country
• Sites: 17

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.

Conditions

Persistent Pregnancy of Unknown Location; Ectopic Pregnancy

Outcome Measures

Primary Outcomes (1)

• 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.

  6 weeks from randomization

Study Arms (3)

Expectant Management

ACTIVE COMPARATOR

Subjects will have their PPUL expectantly managed using serum hCG monitoring.

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.

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.

Drug: Methotrexate

Interventions

Methotrexate DRUG

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.

Empiric treatment with MTX for all; Uterine evacuation with MTX for some

Uterine Evacuation PROCEDURE

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.

Uterine evacuation with MTX for some

Expectant Management OTHER

Pregnancy will be expectantly managed using serum hcg monitoring

Expectant Management

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Augusta University: collaborator
• Penn State University: collaborator
• University of California, San Francisco: collaborator
• University of North Carolina: collaborator
• University of Oklahoma: collaborator
• University of Pennsylvania: collaborator

Study Sites (17)

University of California San Francisco

San Francisco, California, 94115, United States

Location

Denver Health

Denver, Colorado, 80204, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University Of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Wayne State University

Southfield, Michigan, 48034, United States

Location

Washington University

St Louis, Missouri, 63108, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Medical Center - Women's Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• 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.

  PMID: 34342619 DERIVED

MeSH Terms

Conditions

Pregnancy, Ectopic

Interventions

Methotrexate; Watchful Waiting

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Results Point of Contact

• Title: Heping Zhang, PhD
• Organization: Yale University

heping.zhang@yale.edu

203-785-5185

Study Officials

• Esther Eisenberg, MD MPH

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  STUDY DIRECTOR

• Nanette Santoro, MD

  University of Colorado, Denver

  STUDY CHAIR

• Kurt Barnhart, MD MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Michael Diamond, MD

  Augusta University

  STUDY DIRECTOR

• Richard Legro, MD

  Penn State University

  STUDY DIRECTOR

• Marcelle Cedars, MD

  University of California, San Francisco

  STUDY DIRECTOR

• Anne Steiner, MD MPH

  University of North Carolina

  STUDY DIRECTOR

• Karl Hansen, MD PhD

  University of Oklahoma

  STUDY DIRECTOR

• Christos Coutifaris, MD PhD

  University of Pennsylvania

  STUDY DIRECTOR

• Heping Zhang, PhD

  Yale University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: June 2, 2014
• Study Start: July 25, 2014
• Primary Completion: August 1, 2019
• Study Completion: August 19, 2019
• Last Updated: December 8, 2020
• Results First Posted: October 26, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share

Locations

US (17)