Trial Outcomes & Findings for Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location (NCT NCT02152696)

Last Updated: 2020-12-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

255 participants

Primary outcome timeframe

6 weeks from randomization

Results posted on

2020-12-08

Participant Flow

Participant milestones

Participant milestones
Measure	Expectant Management Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring	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.	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.
Overall Study STARTED	86	87	82
Overall Study COMPLETED	86	86	81
Overall Study NOT COMPLETED	0	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Expectant Management n=86 Participants Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring	Uterine Evacuation With MTX for Some n=87 Participants 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.	Empiric Treatment With MTX for All n=82 Participants 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 n=255 Participants Total of all reporting groups
Age, Continuous	32.1 years STANDARD_DEVIATION 5.6 • n=86 Participants	31.2 years STANDARD_DEVIATION 5.9 • n=87 Participants	31.5 years STANDARD_DEVIATION 5.7 • n=82 Participants	31.6 years STANDARD_DEVIATION 5.7 • n=255 Participants
Sex: Female, Male Female	86 Participants n=86 Participants	87 Participants n=87 Participants	82 Participants n=82 Participants	255 Participants n=255 Participants
Sex: Female, Male Male	0 Participants n=86 Participants	0 Participants n=87 Participants	0 Participants n=82 Participants	0 Participants n=255 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=86 Participants	8 Participants n=87 Participants	6 Participants n=82 Participants	17 Participants n=255 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	80 Participants n=86 Participants	75 Participants n=87 Participants	74 Participants n=82 Participants	229 Participants n=255 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=86 Participants	4 Participants n=87 Participants	2 Participants n=82 Participants	9 Participants n=255 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=86 Participants	0 Participants n=87 Participants	0 Participants n=82 Participants	0 Participants n=255 Participants
Race (NIH/OMB) Asian	3 Participants n=86 Participants	10 Participants n=87 Participants	4 Participants n=82 Participants	17 Participants n=255 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=86 Participants	0 Participants n=87 Participants	0 Participants n=82 Participants	0 Participants n=255 Participants
Race (NIH/OMB) Black or African American	37 Participants n=86 Participants	33 Participants n=87 Participants	32 Participants n=82 Participants	102 Participants n=255 Participants
Race (NIH/OMB) White	41 Participants n=86 Participants	40 Participants n=87 Participants	39 Participants n=82 Participants	120 Participants n=255 Participants
Race (NIH/OMB) More than one race	0 Participants n=86 Participants	0 Participants n=87 Participants	0 Participants n=82 Participants	0 Participants n=255 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=86 Participants	4 Participants n=87 Participants	7 Participants n=82 Participants	16 Participants n=255 Participants
Region of Enrollment United States	86 Participants n=86 Participants	87 Participants n=87 Participants	82 Participants n=82 Participants	255 Participants n=255 Participants
Estimated gestational age - week	6.4 weeks STANDARD_DEVIATION 1.8 • n=85 Participants • 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.	6.9 weeks STANDARD_DEVIATION 1.9 • n=83 Participants • 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.	6.7 weeks STANDARD_DEVIATION 2.0 • n=80 Participants • 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.	6.7 weeks STANDARD_DEVIATION 1.9 • n=248 Participants • 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)	661.2 mIU/ml STANDARD_DEVIATION 688.6 • n=86 Participants	561.9 mIU/ml STANDARD_DEVIATION 702.5 • n=87 Participants	633.3 mIU/ml STANDARD_DEVIATION 695.8 • n=82 Participants	618.3 mIU/ml STANDARD_DEVIATION 694.2 • n=255 Participants

PRIMARY outcome

Timeframe: 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 in treatment from the initial management strategy.

Outcome measures

Outcome measures
Measure	Expectant Management n=86 Participants Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring	Uterine Evacuation With MTX for Some n=87 Participants 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.	Empiric Treatment With MTX for All n=82 Participants 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.
Number of Participants With Uneventful Clinical Resolution of a Pregnancy of Unknown Location Without Change From the Initial Management Strategy	31 Participants	42 Participants	45 Participants

Adverse Events

Expectant Management

Serious events: 2 serious events

Other events: 44 other events

Deaths: 0 deaths

Uterine Evacuation With MTX for Some

Serious events: 2 serious events

Other events: 53 other events

Deaths: 0 deaths

Empiric Treatment With MTX for All

Serious events: 0 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Expectant Management n=86 participants at risk Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring	Uterine Evacuation With MTX for Some n=87 participants at risk 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.	Empiric Treatment With MTX for All n=82 participants at risk 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.
Pregnancy, puerperium and perinatal conditions Hospitalization	0.00% 0/86 • 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.	1.1% 1/87 • Number of events 1 • 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.	0.00% 0/82 • 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.
Pregnancy, puerperium and perinatal conditions Salpingectomy	2.3% 2/86 • 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.	0.00% 0/87 • 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.	0.00% 0/82 • 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.
Pregnancy, puerperium and perinatal conditions Right ruptured ectopic pregnancy	0.00% 0/86 • 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.	1.1% 1/87 • Number of events 1 • 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.	0.00% 0/82 • 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.

Other adverse events

Additional Information

Heping Zhang, PhD

Yale University

Phone: 203-785-5185

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Expectant Management n=86 participants at risk Subjects will have their PPUL expectantly managed using serum hCG monitoring. Expectant Management: Pregnancy will be expectantly managed using serum hcg monitoring	Uterine Evacuation With MTX for Some n=87 participants at risk 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.	Empiric Treatment With MTX for All n=82 participants at risk 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.
General disorders Persistent dry cough	3.5% 3/86 • Number of events 3 • 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.	5.7% 5/87 • Number of events 5 • 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.	6.1% 5/82 • Number of events 5 • 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.
General disorders Any Other Side Effects	7.0% 6/86 • Number of events 6 • 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.	4.6% 4/87 • Number of events 4 • 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.	3.7% 3/82 • Number of events 3 • 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.
General disorders One or more adverse event	51.2% 44/86 • Number of events 44 • 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.	60.9% 53/87 • Number of events 53 • 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.	56.1% 46/82 • Number of events 46 • 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.
Gastrointestinal disorders Nausea	25.6% 22/86 • Number of events 22 • 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.	36.8% 32/87 • Number of events 32 • 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.	37.8% 31/82 • Number of events 31 • 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.
Gastrointestinal disorders Vomiting	2.3% 2/86 • Number of events 2 • 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.	12.6% 11/87 • Number of events 11 • 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.	12.2% 10/82 • Number of events 10 • 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.
Reproductive system and breast disorders Pelvic Pain	43.0% 37/86 • Number of events 37 • 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.	48.3% 42/87 • Number of events 42 • 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.	46.3% 38/82 • Number of events 38 • 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.
Gastrointestinal disorders Loss of Appetite	29.1% 25/86 • Number of events 25 • 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.	32.2% 28/87 • Number of events 28 • 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.	28.0% 23/82 • Number of events 23 • 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.
Gastrointestinal disorders Mouth Sores	5.8% 5/86 • Number of events 5 • 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.	6.9% 6/87 • Number of events 6 • 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.	7.3% 6/82 • Number of events 6 • 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.
Gastrointestinal disorders Diarrhea	10.5% 9/86 • Number of events 9 • 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.	24.1% 21/87 • Number of events 21 • 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.	15.9% 13/82 • Number of events 13 • 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.
General disorders Heart Burn/Indigestion	8.1% 7/86 • Number of events 7 • 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.	13.8% 12/87 • Number of events 12 • 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.	6.1% 5/82 • Number of events 5 • 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.
General disorders Hair Loss	4.7% 4/86 • Number of events 4 • 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.	10.3% 9/87 • Number of events 9 • 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.	7.3% 6/82 • Number of events 6 • 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.
Nervous system disorders Headaches	36.0% 31/86 • Number of events 31 • 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.	28.7% 25/87 • Number of events 25 • 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.	32.9% 27/82 • Number of events 27 • 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.
General disorders Fatigue	44.2% 38/86 • Number of events 38 • 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.	43.7% 38/87 • Number of events 38 • 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.	43.9% 36/82 • Number of events 36 • 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.
Surgical and medical procedures Vaginal bleeding	44.2% 38/86 • Number of events 38 • 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.	52.9% 46/87 • Number of events 46 • 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.	47.6% 39/82 • Number of events 39 • 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.
General disorders Dizziness or weakness	20.9% 18/86 • Number of events 18 • 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.	31.0% 27/87 • Number of events 27 • 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.	20.7% 17/82 • Number of events 17 • 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.
General disorders Shoulder or back pain	16.3% 14/86 • Number of events 14 • 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.	20.7% 18/87 • Number of events 18 • 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.	14.6% 12/82 • Number of events 12 • 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.