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| ID | Type | Description | Link |
|---|---|---|---|
| 2U10HD055925-06 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| Augusta University | OTHER |
| Penn State University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Expectant Management | Active Comparator | Subjects will have their PPUL expectantly managed using serum hCG monitoring. |
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| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco | San Francisco | California | 94115 | United States | ||
| Denver Health |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34342619 | Derived | 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. |
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IPD will be shared with other researchers through the NICHD DASH system. It will be available 6 months after publication of the primary results.
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| ID | Title | Description |
|---|---|---|
| FG000 | Expectant Management | Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring |
| FG001 | Uterine Evacuation With MTX for Some |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 9, 2019 |
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| University of California, San Francisco |
| OTHER |
| University of North Carolina | OTHER |
| University of Oklahoma | OTHER |
| University of Pennsylvania | OTHER |
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| 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. |
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| Expectant Management | Other | Pregnancy will be expectantly managed using serum hcg monitoring |
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| Yale University |
| Study Director |
| Denver |
| Colorado |
| 80204 |
| United States |
| Yale University | New Haven | Connecticut | 06520 | United States |
| University of South Florida | Tampa | Florida | 33606 | United States |
| Augusta University | Augusta | Georgia | 30912 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| University Of Illinois at Chicago | Chicago | Illinois | 60612 | United States |
| Wayne State University | Southfield | Michigan | 48034 | United States |
| Washington University | St Louis | Missouri | 63108 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| University of North Carolina | Chapel Hill | North Carolina | 27599 | United States |
| Carolinas Medical Center - Women's Institute | Charlotte | North Carolina | 28204 | United States |
| Duke University | Durham | North Carolina | 27708 | United States |
| University of Oklahoma | Oklahoma City | Oklahoma | 73104 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Greenville Health System | Greenville | South Carolina | 29605 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
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.
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.
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.
| FG002 | 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. 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Expectant Management | Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring |
| BG001 | 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. 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. 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. |
| BG002 | 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. 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Estimated gestational age - week | Data were missing for 1 patient in the Expectant management group, 4 in the Uterine evacuation with MTX for some group and 2 in the Empiric treatment with MTX for all. | Mean | Standard Deviation | weeks |
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| First hCG value at screening (mIU/ml) | Mean | Standard Deviation | mIU/ml |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 6 weeks from randomization |
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The period of time over which the adverse events were collected is: from the initiation of the study procedures to the end of the study treatment follow-up, which is about an average of 42 days following the last administration of study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Expectant Management | Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring | 0 | 86 | 2 | 86 | 44 | 86 |
| EG001 | 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. 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. 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. | 0 | 87 | 2 | 87 | 53 | 87 |
| EG002 | 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. 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. | 0 | 82 | 0 | 82 | 46 | 82 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization | Pregnancy, puerperium and perinatal conditions | MedDra | Systematic Assessment | Hospitalization.ED visit pelvic ultrasound revealed right adnexal mass concerning for tubal pregnancy. |
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| Salpingectomy | Pregnancy, puerperium and perinatal conditions | MedDra | Systematic Assessment |
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| Right ruptured ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDra | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| One or more adverse event | General disorders | MedDra | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDra | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDra | Systematic Assessment |
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| Pelvic Pain | Reproductive system and breast disorders | MedDra | Systematic Assessment |
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| Loss of Appetite | Gastrointestinal disorders | MedDra | Systematic Assessment |
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| Mouth Sores | Gastrointestinal disorders | MedDra | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDra | Systematic Assessment |
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| Heart Burn/Indigestion | General disorders | MedDra | Systematic Assessment |
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| Hair Loss | General disorders | MedDra | Systematic Assessment |
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| Headaches | Nervous system disorders | MedDra | Systematic Assessment |
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| Fatigue | General disorders | MedDra | Systematic Assessment |
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| Vaginal bleeding | Surgical and medical procedures | MedDra | Systematic Assessment |
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| Dizziness or weakness | General disorders | MedDra | Systematic Assessment |
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| Shoulder or back pain | General disorders | MedDra | Systematic Assessment |
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| Persistent dry cough | General disorders | MedDra | Systematic Assessment |
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| Any Other Side Effects | General disorders | MedDra | Systematic Assessment | Including sore throats, cough, constipation, depression, lower back pain, pain in breasts/shoulder, and other unspecified events. These events were recorded in free text, not separated. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Heping Zhang, PhD | Yale University | 203-785-5185 | heping.zhang@yale.edu |
| Sep 17, 2020 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D011271 | Pregnancy, Ectopic |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D008727 | Methotrexate |
| D057832 | Watchful Waiting |
| ID | Term |
|---|---|
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D017063 | Outcome Assessment, Health Care |
| D010043 | Outcome and Process Assessment, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
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