Ectopic PregnancyPhase 3NCT01855568
Methotrexate Treatment for Ectopic Pregnancy
A Phase 3 study testing Single-dose Methotrexate and Two-dose methotrexate protocol in people with Ectopic Pregnancy, run by CHA University at 1 site in South Korea.
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. Read more about this study
- Who is it for?
- Ages 19 to 55 years, women only
- Conditions the study is for
- Ectopic Pregnancy
- What is being tested?
- Single-dose Methotrexate and Two-dose methotrexate protocol
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2013to Apr 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Two-dose and Single-dose Methotrexate Protocol for Ectopic Pregnancy: a Randomized Controlled Trial
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.
- Conditions
- Ectopic Pregnancy
- Being tested
- Single-dose Methotrexate, Two-dose methotrexate protocol
- Medical subject headings
- Pregnancy, Ectopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single-dose MethotrexateProcedure or surgery
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.
Two-dose methotrexate protocolProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Single-dose methotrexate protocol | Experimental | 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. Receives: Procedure: Single-dose Methotrexate |
| Two-dose methotrexate protocol | Experimental | 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. Receives: Procedure: Two-dose methotrexate protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 8 weeks (normal recovery time after treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2013 (estimated)
- Study startMay 2013
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ectopic PregnancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- CHA University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Taejong Song, CHA University
- Investigators
- Taejong Song, M.D., Principal investigator, CHA Gangnam Medical Center, Seoul, Republic of Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01855568
- Sponsor's protocol ID
- KNC13-006
- Status last verified
- Jan 2016
- First submitted
- 10 May 2013
- Last updated
- 22 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26701971
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Two-dose and Single-dose Methotrexate Protocol for Ectopic Pregnancy: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01855568
- Acronym / sponsor ID
- KNC13-006
- Conditions
- Ectopic Pregnancy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- CHA UniversityUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 16 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single-dose methotrexate protocol | Experimental | Procedure: Single-dose MethotrexateParticipants 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. |
| Two-dose methotrexate protocol | Experimental | Procedure: Two-dose methotrexate protocolParticipants 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. |
Who may qualify
- Ages
- 19 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single-dose MethotrexateParticipants 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 or surgery | Single-dose methotrexate protocol |
| Two-dose methotrexate protocolParticipants 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 or surgery | Two-dose methotrexate protocol |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2016.
- Derived from this study: PubMed 26701971Song 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Taejong Song, M.D. principal investigator
CHA Gangnam Medical Center, Seoul, Republic of Korea
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Single-dose Methotrexate and Two-dose methotrexate protocol in people with Ectopic Pregnancy, run by CHA University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
treatment success (time frame: Up to 8 weeks (normal recovery time after treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01855568, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2016.