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Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location (ACTorNOT)

Primary Purpose

Persistent Pregnancy of Unknown Location, Ectopic Pregnancy

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Methotrexate
Uterine Evacuation
Expectant Management
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Persistent Pregnancy of Unknown Location

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of California San Francisco
  • Denver Health
  • Yale University
  • University of South Florida
  • Augusta University
  • Northwestern University
  • University Of Illinois at Chicago
  • Wayne State University
  • Washington University
  • University of Rochester
  • University of North Carolina
  • Carolinas Medical Center - Women's Institute
  • Duke University
  • University of Oklahoma
  • University of Pennsylvania
  • Greenville Health System
  • University of Utah

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Expectant Management

Uterine evacuation with MTX for some

Empiric treatment with MTX for all

Arm Description

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

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
May 28, 2014
Last Updated
November 18, 2020
Sponsor
Yale University
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
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1. Study Identification

Unique Protocol Identification Number
NCT02152696
Brief Title
Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location
Acronym
ACTorNOT
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

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
July 25, 2014 (Actual)
Primary Completion Date
August 2019 (Actual)
Study Completion Date
August 19, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
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

4. Oversight

Data Monitoring Committee
Yes

5. 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Persistent Pregnancy of Unknown Location, Ectopic Pregnancy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
255 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Expectant Management
Arm Type
Active Comparator
Arm Description
Subjects will have their PPUL expectantly managed using serum hCG monitoring.
Arm Title
Uterine evacuation with MTX for some
Arm Type
Active Comparator
Arm 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.
Arm Title
Empiric treatment with MTX for all
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Uterine Evacuation
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Expectant Management
Intervention Description
Pregnancy will be expectantly managed using serum hcg monitoring
Primary Outcome Measure Information:
Title
Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy
Description
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.
Time Frame
6 weeks from randomization

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Esther Eisenberg, MD MPH
Organizational Affiliation
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Nanette Santoro, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Kurt Barnhart, MD MSCE
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Diamond, MD
Organizational Affiliation
Augusta University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Richard Legro, MD
Organizational Affiliation
Penn State University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Marcelle Cedars, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Anne Steiner, MD MPH
Organizational Affiliation
University of North Carolina
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Karl Hansen, MD PhD
Organizational Affiliation
University of Oklahoma
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Christos Coutifaris, MD PhD
Organizational Affiliation
University of Pennsylvania
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Heping Zhang, PhD
Organizational Affiliation
Yale University
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Denver Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University Of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Wayne State University
City
Southfield
State/Province
Michigan
ZIP/Postal Code
48034
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Carolinas Medical Center - Women's Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27708
Country
United States
Facility Name
University of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Greenville Health System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD will be shared with other researchers through the NICHD DASH system. It will be available 6 months after publication of the primary results.
Citations:
PubMed Identifier
34342619
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.
Results Reference
derived

Learn more about this trial

Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location

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