Methotrexate Treatment for Ectopic Pregnancy

Ectopic Pregnancy Clinical Trial

Official title:

Comparison of Two-dose and Single-dose Methotrexate Protocol for Ectopic Pregnancy: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01855568
• Other study ID #: KNC13-006
• Status: Completed
• Phase: Phase 3
• First received: May 10, 2013
• Last updated: January 21, 2016
• Start date: May 2013
• Est. completion date: April 2015

Study information

• Verified date: January 2016
• Source: CHA University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years to 55 Years

Eligibility

Inclusion Criteria:

• tubal pregnancy

• tubal pregnancy except interstitial pregnancy

• a pretreatment ß-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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ectopic Pregnancy
• Pregnancy, Ectopic

Intervention

Procedure:
• Single-dose Methotrexate
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 ß-hCG levels were then measured on day 4 and 7. If there was at least 15% ß-hCG drop between day 4 and 7, the treatment was deemed successful and the participants were then followed with weekly ß-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 ß-hCG levels were then measured on day 11 and 14. Participants were referred for surgical treatment if ß-hCG levels fell <15% between day 11 and 14.
• Two-dose methotrexate protocol
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 ß-hCG levels did not fall 15% between day 4 and 7 after two-dosing. A fourth dose was administered on day 11 if ß-hCG levels fell <15% between day 7 and 11. Then, a final ß-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.

Locations

Country	Name	City	State
Korea, Republic of	CHA Gangnam Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
CHA University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	treatment success	Participants in both groups were considered a treatment success if ß-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.	Up to 8 weeks (normal recovery time after treatment)	No