how many doses of methotrexate for ectopic pregnancy?

Methotrexate Treatment for Ectopic Pregnancy
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ClinicalTrials.gov Identifier: NCT01855568
Recruitment Status : Completed
First Posted : May 16, 2013
Last Update Posted : January 22, 2016
Sponsor:
CHA University
Information provided by (Responsible Party):
Taejong Song, CHA University

Study Details
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Study Description
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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.

Condition or disease Intervention/treatment Phase
Ectopic Pregnancy Procedure: Single-dose Methotrexate Procedure: Two-dose methotrexate protocol Phase 3

Study Design
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Study Type : Interventional (Clinical Trial)
Actual Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of Two-dose and Single-dose Methotrexate Protocol for Ectopic Pregnancy: a Randomized Controlled Trial
Study Start Date : May 2013
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ectopic Pregnancy Pregnancy
Drug Information available for: Methotrexate
Genetic and Rare Diseases Information Center resources: Ectopic Pregnancy
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Single-dose methotrexate protocol
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.
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 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.

Experimental: 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 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.
Procedure: 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 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.



Outcome Measures
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Primary Outcome Measures :

treatment success [ Time Frame: Up to 8 weeks (normal recovery time after treatment) ]
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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study: 19 Years to 55 Years (Adult)
Sexes Eligible for Study: Female
Accepts Healthy Volunteers: No
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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01855568

Locations
Korea, Republic of
CHA Gangnam Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
CHA University
Investigators
Principal Investigator: Taejong Song, M.D. CHA Gangnam Medical Center, Seoul, Republic of Korea
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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.

Responsible Party: Taejong Song, Professor, CHA University
ClinicalTrials.gov Identifier: NCT01855568 History of Changes
Other Study ID Numbers: KNC13-006
First Posted: May 16, 2013 Key Record Dates
Last Update Posted: January 22, 2016
Last Verified: January 2016
Additional relevant MeSH terms:
Pregnancy, Ectopic
Cardiac Complexes, Premature
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Pathologic Processes
Pregnancy Complications
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors


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