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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02152696
Recruitment Status : Completed
First Posted : June 2, 2014
Results First Posted : October 26, 2020
Last Update Posted : December 8, 2020
Sponsor:
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 Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Persistent Pregnancy of Unknown Location
Ectopic Pregnancy
Interventions Drug: Methotrexate
Procedure: Uterine Evacuation
Other: Expectant Management
Enrollment 255
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Expectant Management Uterine Evacuation With MTX for Some Empiric Treatment With MTX for All
Hide Arm/Group Description

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

Expectant Management: Pregnancy will be 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.

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.

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.

Period Title: Overall Study
Started 86 87 82
Completed 86 86 81
Not Completed 0 1 1
Arm/Group Title Expectant Management Uterine Evacuation With MTX for Some Empiric Treatment With MTX for All Total
Hide Arm/Group Description

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

Expectant Management: Pregnancy will be 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.

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 86 87 82 255
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 86 participants 87 participants 82 participants 255 participants
32.1  (5.6) 31.2  (5.9) 31.5  (5.7) 31.6  (5.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants 87 participants 82 participants 255 participants
Female
86
 100.0%
87
 100.0%
82
 100.0%
255
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants 87 participants 82 participants 255 participants
Hispanic or Latino
3
   3.5%
8
   9.2%
6
   7.3%
17
   6.7%
Not Hispanic or Latino
80
  93.0%
75
  86.2%
74
  90.2%
229
  89.8%
Unknown or Not Reported
3
   3.5%
4
   4.6%
2
   2.4%
9
   3.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 86 participants 87 participants 82 participants 255 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   3.5%
10
  11.5%
4
   4.9%
17
   6.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
37
  43.0%
33
  37.9%
32
  39.0%
102
  40.0%
White
41
  47.7%
40
  46.0%
39
  47.6%
120
  47.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
5
   5.8%
4
   4.6%
7
   8.5%
16
   6.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 86 participants 87 participants 82 participants 255 participants
86
 100.0%
87
 100.0%
82
 100.0%
255
 100.0%
Estimated gestational age - week   [1] 
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 85 participants 83 participants 80 participants 248 participants
6.4  (1.8) 6.9  (1.9) 6.7  (2.0) 6.7  (1.9)
[1]
Measure Analysis Population Description: 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.
First hCG value at screening (mIU/ml)  
Mean (Standard Deviation)
Unit of measure:  mIU/ml
Number Analyzed 86 participants 87 participants 82 participants 255 participants
661.2  (688.6) 561.9  (702.5) 633.3  (695.8) 618.3  (694.2)
1.Primary Outcome
Title Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Expectant Management Uterine Evacuation With MTX for Some Empiric Treatment With MTX for All
Hide Arm/Group Description:

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

Expectant Management: Pregnancy will be 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.

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.

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.

Overall Number of Participants Analyzed 86 87 82
Measure Type: Count of Participants
Unit of Measure: Participants
31
  36.0%
42
  48.3%
45
  54.9%
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Expectant Management Uterine Evacuation With MTX for Some Empiric Treatment With MTX for All
Hide Arm/Group Description

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

Expectant Management: Pregnancy will be 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.

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.

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.

All-Cause Mortality
Expectant Management Uterine Evacuation With MTX for Some Empiric Treatment With MTX for All
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/86 (0.00%)      0/87 (0.00%)      0/82 (0.00%)    
Hide Serious Adverse Events
Expectant Management Uterine Evacuation With MTX for Some Empiric Treatment With MTX for All
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/86 (2.33%)      2/87 (2.30%)      0/82 (0.00%)    
Pregnancy, puerperium and perinatal conditions       
Hospitalization  1 [1]  0/86 (0.00%)  0 1/87 (1.15%)  1 0/82 (0.00%)  0
Salpingectomy  1  2/86 (2.33%)  0/87 (0.00%)  0 0/82 (0.00%)  0
Right ruptured ectopic pregnancy  1  0/86 (0.00%)  0 1/87 (1.15%)  1 0/82 (0.00%)  0
1
Term from vocabulary, MedDra
Indicates events were collected by systematic assessment
[1]
Hospitalization.ED visit pelvic ultrasound revealed right adnexal mass concerning for tubal pregnancy.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Expectant Management Uterine Evacuation With MTX for Some Empiric Treatment With MTX for All
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/86 (51.16%)      53/87 (60.92%)      46/82 (56.10%)    
Gastrointestinal disorders       
Nausea  1  22/86 (25.58%)  22 32/87 (36.78%)  32 31/82 (37.80%)  31
Vomiting  1  2/86 (2.33%)  2 11/87 (12.64%)  11 10/82 (12.20%)  10
Loss of Appetite  1  25/86 (29.07%)  25 28/87 (32.18%)  28 23/82 (28.05%)  23
Mouth Sores  1  5/86 (5.81%)  5 6/87 (6.90%)  6 6/82 (7.32%)  6
Diarrhea  1  9/86 (10.47%)  9 21/87 (24.14%)  21 13/82 (15.85%)  13
General disorders       
One or more adverse event  1  44/86 (51.16%)  44 53/87 (60.92%)  53 46/82 (56.10%)  46
Heart Burn/Indigestion  1  7/86 (8.14%)  7 12/87 (13.79%)  12 5/82 (6.10%)  5
Hair Loss  1  4/86 (4.65%)  4 9/87 (10.34%)  9 6/82 (7.32%)  6
Fatigue  1  38/86 (44.19%)  38 38/87 (43.68%)  38 36/82 (43.90%)  36
Dizziness or weakness  1  18/86 (20.93%)  18 27/87 (31.03%)  27 17/82 (20.73%)  17
Shoulder or back pain  1  14/86 (16.28%)  14 18/87 (20.69%)  18 12/82 (14.63%)  12
Persistent dry cough  1  3/86 (3.49%)  3 5/87 (5.75%)  5 5/82 (6.10%)  5
Any Other Side Effects  1 [1]  6/86 (6.98%)  6 4/87 (4.60%)  4 3/82 (3.66%)  3
Nervous system disorders       
Headaches  1  31/86 (36.05%)  31 25/87 (28.74%)  25 27/82 (32.93%)  27
Reproductive system and breast disorders       
Pelvic Pain  1  37/86 (43.02%)  37 42/87 (48.28%)  42 38/82 (46.34%)  38
Surgical and medical procedures       
Vaginal bleeding  1  38/86 (44.19%)  38 46/87 (52.87%)  46 39/82 (47.56%)  39
1
Term from vocabulary, MedDra
Indicates events were collected by systematic assessment
[1]
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Heping Zhang, PhD
Organization: Yale University
Phone: 203-785-5185
EMail: heping.zhang@yale.edu
Layout table for additonal information
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02152696    
Other Study ID Numbers: 2000023590
2U10HD055925-06 ( U.S. NIH Grant/Contract )
First Submitted: May 28, 2014
First Posted: June 2, 2014
Results First Submitted: August 17, 2020
Results First Posted: October 26, 2020
Last Update Posted: December 8, 2020