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Methotrexate Treatment for Ectopic Pregnancy

Primary Purpose

Ectopic Pregnancy

Status
Completed
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Single-dose Methotrexate
Two-dose methotrexate protocol
Sponsored by
CHA University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ectopic Pregnancy

Eligibility Criteria

19 Years - 55 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • tubal pregnancy
  • tubal pregnancy except interstitial pregnancy
  • a pretreatment β-hCG level <15000 mIU/mL
  • a gestational sac with a largest diameter <4 cm
  • hemodynamically stable status
  • agreement to methotrexate treatment and follow up

Exclusion Criteria:

  • heterotrophic pregnancy
  • a presence of embryonic cardiac motion
  • clinically or sonographically suspected tubal rupture
  • laboratory tests showing possible deleterious effects of methotrexate treatment on organ functions

Sites / Locations

  • CHA Gangnam Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Single-dose methotrexate protocol

Two-dose methotrexate protocol

Arm Description

Participants in the "single-dose protocol" group received intramuscular methotrexate at single dose of 50 mg/m2 on day 0 (the initial day of treatment). The β-hCG levels were then measured on day 4 and 7. If there was at least 15% β-hCG drop between day 4 and 7, the treatment was deemed successful and the participants were then followed with weekly β-hCG measurements until the results was negative. If a 15% drop on day 4 and 7 did not occur, a second dose was administrated on day 7 and β-hCG levels were then measured on day 11 and 14. Participants were referred for surgical treatment if β-hCG levels fell <15% between day 11 and 14.

Participants in the "two-dose protocol" group received intramuscular methotrexate twice at dose of 50 mg/m2 on day 0 and 4. A third dose of methotrexate was given on day 7 if β-hCG levels did not fall 15% between day 4 and 7 after two-dosing. A fourth dose was administered on day 11 if β-hCG levels fell <15% between day 7 and 11. Then, a final β-hCG level was checked on day 14. If a 15% drop was not seen, the medical treatment was deemed refractory and the patients were referred for surgical treatment.

Outcomes

Primary Outcome Measures

treatment success
Participants in both groups were considered a treatment success if β-hCG levels resolved to <5 mIU/mL without surgical intervention. The cases of participants who underwent surgical intervention were considered to have had treatment failure.

Secondary Outcome Measures

Full Information

First Posted
May 10, 2013
Last Updated
January 21, 2016
Sponsor
CHA University
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1. Study Identification

Unique Protocol Identification Number
NCT01855568
Brief Title
Methotrexate Treatment for Ectopic Pregnancy
Official Title
Comparison of Two-dose and Single-dose Methotrexate Protocol for Ectopic Pregnancy: a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
CHA University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Ectopic pregnancy is an important cause of maternal morbidity and occasionally mortality. Deaths associated with ectopic pregnancy have declined, though approximately 75% of deaths in the first trimester and 9-13% of all pregnancy-related deaths are associated ectopic pregnancy. The main stays of management for ectopic pregnancy were surgery and medical treatment. Medical management with systemic methotrexate administration avoids the inherent morbidity of anesthesia and surgery is cost-effective, and also offers success rates comparable to surgical management, with no loss in future potential fertility. However, although medical management using methotrexate is used commonly, there is no solid consensus regarding dose protocol. Currently, there are three methotrexate protocols for the treatment of an ectopic pregnancy, "multi-dose", "single-dose", or "two-dose". Among them, the multi-dose protocol includes the administration of 4 methotrexate doses alternating with leucovorin (rescue regimen). As a result of the multiple dosing of methotrexate, side effects are more common. In contrast, the advantages of the single-dose protocol include elimination of a rescue regimen, lower incidence of adverse effects, and better compliance. However, the single-dose protocol was found to be associated with a considerably lower success rate as compared with the multi-dose protocol (88% versus 93%) in a recent meta-analysis. The two-dose protocol, which it balances efficacy and safety/convenience, was described as a cross between the multi-dose and single-dose protocols. However, there were a few studies comparing between single-dose and two-dose protocol. The purpose of this prospective randomized trial was to compared the success rates of single-dose and two-dose methotrexate protocol for the treatment of tubal ectopic pregnancy.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Single-dose methotrexate protocol
Arm Type
Experimental
Arm Description
Participants in the "single-dose protocol" group received intramuscular methotrexate at single dose of 50 mg/m2 on day 0 (the initial day of treatment). The β-hCG levels were then measured on day 4 and 7. If there was at least 15% β-hCG drop between day 4 and 7, the treatment was deemed successful and the participants were then followed with weekly β-hCG measurements until the results was negative. If a 15% drop on day 4 and 7 did not occur, a second dose was administrated on day 7 and β-hCG levels were then measured on day 11 and 14. Participants were referred for surgical treatment if β-hCG levels fell <15% between day 11 and 14.
Arm Title
Two-dose methotrexate protocol
Arm Type
Experimental
Arm Description
Participants in the "two-dose protocol" group received intramuscular methotrexate twice at dose of 50 mg/m2 on day 0 and 4. A third dose of methotrexate was given on day 7 if β-hCG levels did not fall 15% between day 4 and 7 after two-dosing. A fourth dose was administered on day 11 if β-hCG levels fell <15% between day 7 and 11. Then, a final β-hCG level was checked on day 14. If a 15% drop was not seen, the medical treatment was deemed refractory and the patients were referred for surgical treatment.
Intervention Type
Procedure
Intervention Name(s)
Single-dose Methotrexate
Intervention Description
Participants in the "single-dose protocol" group received intramuscular methotrexate at single dose of 50 mg/m2 on day 0 (the initial day of treatment). The β-hCG levels were then measured on day 4 and 7. If there was at least 15% β-hCG drop between day 4 and 7, the treatment was deemed successful and the participants were then followed with weekly β-hCG measurements until the results was negative. If a 15% drop on day 4 and 7 did not occur, a second dose was administrated on day 7 and β-hCG levels were then measured on day 11 and 14. Participants were referred for surgical treatment if β-hCG levels fell <15% between day 11 and 14.
Intervention Type
Procedure
Intervention Name(s)
Two-dose methotrexate protocol
Intervention Description
Participants in the "two-dose protocol" group received intramuscular methotrexate twice at dose of 50 mg/m2 on day 0 and 4. A third dose of methotrexate was given on day 7 if β-hCG levels did not fall 15% between day 4 and 7 after two-dosing. A fourth dose was administered on day 11 if β-hCG levels fell <15% between day 7 and 11. Then, a final β-hCG level was checked on day 14. If a 15% drop was not seen, the medical treatment was deemed refractory and the patients were referred for surgical treatment.
Primary Outcome Measure Information:
Title
treatment success
Description
Participants in both groups were considered a treatment success if β-hCG levels resolved to <5 mIU/mL without surgical intervention. The cases of participants who underwent surgical intervention were considered to have had treatment failure.
Time Frame
Up to 8 weeks (normal recovery time after treatment)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: tubal pregnancy tubal pregnancy except interstitial pregnancy a pretreatment β-hCG level <15000 mIU/mL a gestational sac with a largest diameter <4 cm hemodynamically stable status agreement to methotrexate treatment and follow up Exclusion Criteria: heterotrophic pregnancy a presence of embryonic cardiac motion clinically or sonographically suspected tubal rupture laboratory tests showing possible deleterious effects of methotrexate treatment on organ functions
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Taejong Song, M.D.
Organizational Affiliation
CHA Gangnam Medical Center, Seoul, Republic of Korea
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHA Gangnam Medical Center
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
26701971
Citation
Song T, Kim MK, Kim ML, Jung YW, Yun BS, Seong SJ. Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: a randomized controlled trial. Hum Reprod. 2016 Feb;31(2):332-8. doi: 10.1093/humrep/dev312. Epub 2015 Dec 23.
Results Reference
derived

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Methotrexate Treatment for Ectopic Pregnancy

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