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

• ClinicalTrials.gov Identifier: NCT02152696
• Recruitment Status: Active, not recruiting
• First Posted: June 2, 2014
• Last Update Posted: June 18, 2019
• 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
• Information provided by (Responsible Party): Yale University

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.

Condition or disease	Intervention/treatment	Phase
Persistent Pregnancy of Unknown Location; Ectopic Pregnancy	Drug: Methotrexate; Procedure: Uterine Evacuation; Other: Expectant Management	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 255 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 2014
• Estimated Primary Completion Date: August 2019
• Estimated Study Completion Date: September 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Expectant Management; Subjects will have their PPUL expectantly managed using serum hCG monitoring.	Other: Expectant Management; Pregnancy will be expectantly managed using serum hcg monitoring
Active Comparator: Uterine evacuation with MTX for some; 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; 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.; Procedure: Uterine Evacuation; 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.
Active Comparator: Empiric treatment with MTX for all; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. 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 from the initial management strategy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

University of California San Francisco

San Francisco, California, United States, 94115

United States, Colorado

Denver Health

Denver, Colorado, United States, 80204

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06520

United States, Florida

University of South Florida

Tampa, Florida, United States, 33606

United States, Georgia

Augusta University

Augusta, Georgia, United States, 30912

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

University Of Illinois at Chicago

Chicago, Illinois, United States, 60612

United States, Michigan

Wayne State University

Southfield, Michigan, United States, 48034

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63108

United States, New York

University of Rochester

Rochester, New York, United States, 14642

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Carolinas Medical Center - Women's Institute

Charlotte, North Carolina, United States, 28204

Duke University

Durham, North Carolina, United States, 27708

United States, Oklahoma

University of Oklahoma

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Greenville Health System

Greenville, South Carolina, United States, 29605

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

Yale University

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

Investigators

• Study Director: Esther Eisenberg, MD MPH; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Study Chair: Nanette Santoro, MD; University of Colorado, Denver
• Principal Investigator: Kurt Barnhart, MD MSCE; University of Pennsylvania
• Study Director: 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

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02152696 History of Changes
• Other Study ID Numbers: ACTorNOT
• First Posted: June 2, 2014
• Last Update Posted: June 18, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

Additional relevant MeSH terms:

Pregnancy, Ectopic; Cardiac Complexes, Premature; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pregnancy Complications; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors