Ignite Creation Date:
2024-05-05 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00129506
Status:
COMPLETED
Last Update Posted:
2018-06-11
First Post:
2005-08-09
Brief Title:
Comparing Methotrexate Followed by Misoprostol to Misoprostol Alone for Early Abortion
Sponsor:
Wiebe Ellen MD
Organization:
Wiebe Ellen MD
Study Overview
Official Title:
Comparing Methotrexate Followed by Misoprostol to Misoprostol Alone for Early Abortion
Status:
COMPLETED
Status Verified Date:
2018-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background In most countries in which abortion is legal medical abortions are induced with mifepristone and misoprostol Since mifepristone is expensive and unavailable in many countries it is important to find other regimens Methotrexate which is used with misoprostol in Canada is also difficult to obtain in many countries Misoprostol is inexpensive and available in almost all countries A report from Nigeria found that 98 of 100 women aborted within 24 hours of using misoprostol given both sublingually and vaginally
Method This will be a randomized controlled trial of the usual regimen used in Canada methotrexate 50 mgm2 intramuscularly IM followed three days later by 800 mcg vaginal misoprostol to the Nigerian regimen of 400 mcg sublingual misoprostol with 400 mcg vaginal misoprostol The main outcome measure will be a completed abortion within the first week with secondary outcome measures including total surgery rate time to abortion complications pain side effects and patient satisfaction
Rationale If the investigators can find an inexpensive easily available method of medical abortion it will save many lives in third world countries
Method This will be a randomized controlled trial of the usual regimen used in Canada methotrexate 50 mgm2 intramuscularly IM followed three days later by 800 mcg vaginal misoprostol to the Nigerian regimen of 400 mcg sublingual misoprostol with 400 mcg vaginal misoprostol The main outcome measure will be a completed abortion within the first week with secondary outcome measures including total surgery rate time to abortion complications pain side effects and patient satisfaction
Rationale If the investigators can find an inexpensive easily available method of medical abortion it will save many lives in third world countries
Detailed Description:
BackgroundRationale
Medical abortions induced with either mifepristone or methotrexate and then followed by misoprostol are becoming more common Although mifepristone is the preferred drug used to initiate the abortion in Europe parts of Asia and in the US it is not available in many parts of the world such as Canada South America and most of Africa While methotrexate is an acceptable and more widely available alternative concerns about the safety of administration have discouraged some providers from using it The cost of either mifepristone or methotrexate may also be barriers to widespread use Misoprostol is inexpensive and easily available and is used alone for abortion both by the women themselves and by medical providers Effective use of a single safe medication will reduce the number of medications women are exposed to
Reported effectiveness rates for misoprostol alone in terminating pregnancies less than 8 weeks range from 64 to 94 with varying doses and protocols Use of misoprostol in early pregnancy is associated with an increased risk of Mobius syndrome in infants For this reason it is important that the most effective regimen is used for abortion to prevent failures
A summary of the published protocols and results are as follows A rate of 913 was found using 800 mcg vaginally every 24 hours for three doses with higher effectiveness before 42 days gestation A dose of 400 mcg sublingual misoprostol repeated every 24 hours for three doses resulted in 86 success When mifepristone followed by 400 mcg misoprostol orally was compared to 800 mcg misoprostol vaginally the effectiveness rate of the misoprostol alone was 88 and there were more prostaglandin side effects compared to the combined drug regimen These side effects were reduced with prophylactic acetominophen and loperamide Another centre reported a 908 effectiveness rate with two doses of 800 mcg misoprostol vaginally One study assessed women after each dose of 800 mcg vaginal misoprostol and found that only 718 aborted after one dose and 921 aborted after multiple doses When 800 mcg vaginally was repeated every 48 hours for three doses an effectiveness rate of 936 was obtained The same rate was obtained using 1000 mcg When only 600 mcg vaginally was used the effectiveness rate was only 64 repeating the dose every 8 hours did not improve the effectiveness Similar rates were found for adolescents
One proposed hypothesis for the 64-94 range in effectiveness between these various protocols is that sublingual misoprostol has a higher peak serum concentration than oral or vaginal misoprostol In other words the mean time to peak concentration for sublingual misoprostol is similar to oral misoprostol at 26 minutes and the area under the MPA curve is similar to moistened vaginal misoprostol
The regimen planned for this study is a one-step procedure reported at the International Consortium for Medical Abortion meeting in Johannesburg October 2004 by Iheoni Obineche He reported a series of 80 cases in which 79 988 aborted within 12 hours of receiving 400 mcg vaginal misoprostol after a thorough vaginal cleanse plus 400 mcg sublingual misoprostol administered at the same time This will be compared to the standard protocol based on the National Abortion Federation and SOGC which is 50mgm2 of methotrexate injected intramuscularly followed by misoprostol 800mcg per vaginal 4-7 days later
Rationale
In countries where abortion is illegal and common such as those in Africa and South America it is important to find a regimen using misoprostol alone which has a higher completion rate than those regimens usually used
Trial Objectives
The primary objective of this study is to determine if misoprostol alone using this regimen is as effective as the investigators current practice of methotrexate followed by misoprostol for early abortion The secondary objectives are to compare side effects and to assess acceptability
Study Design and Duration
This is a randomized controlled open-label trial Women requesting medical termination of pregnancy at 7 weeks gestation or less will be recruited
The study protocol risks benefits visit schedule and consent will be reviewed with each potential subject The informed consent will include the statement if the treatment does not work I have been advised to agree to a surgical abortion A haemoglobin and Rh factor will be obtained and reviewed A focussed history and physical examination will be performed Gestational dating will be done by endovaginal ultrasound using the following criteria gestational age days mean sac diameter mm 30 or embryonic pole mm 42 Mean sac diameter is used only if there is no embryonic pole This method has been described by Rossavik and Goldstein
Randomization will be performed by using a computer generated list of block random numbers and sealed numbered opaque envelopes will be prepared by a staff member not involved in the informationconsent process
In both groups women who are Rh negative will receive 120 g RhD immune globulin on Day 1 The methotrexatemisoprostol group will be given 50 mgm2 methotrexate and both written and oral instructions At least 72 hours after the methotrexate Day 4-7 they will be asked to moisten four 200 g tablets of misoprostol with a few drops of water each and insert them into the vagina On Day 1 the misoprostol-only group will receive 400 g misoprostol sublingually and the doctor will use a speculum and warm water to cleanse the vagina moisten 400 g misoprostol with warm water and place it in the vaginal fornices All women will also be given six tablets of acetaminophen with codeine two tablets of diphenhydramine and six tablets of 400 mg ibuprofen to use for side effects
All subjects will return to the office within 7 days of having the misoprostol and have another vaginal ultrasound If they have not aborted they will be offered three options waiting using additional doses of misoprostol or surgery If the abortion is failed as evidenced by embryonic cardiac activity on Day 15 these women will be scheduled for surgical aspiration At the first follow-up visit information will be obtained about completion of the abortion and then about the womans experience of bleeding pain and side effects Pain will be measured by an 11-point numeric pain scale using the question On a scale of 0 to 10 where 0 is no pain and 10 is pain as bad as it can be what was the worst pain like for you They will be asked If you were in the same situation would you choose a medical or surgical abortion If given the choice would you choose the same medications you received in this study These scales and questions have been reported in other studies
The main outcome measure is effectiveness after the first dose of misoprostol measured by the number of abortions completed at the first follow-up visit The investigators will also compare the rate of surgery the time taken to abort based on history side effects pain and satisfaction Previous studies have had about 86 of women prefer a medical abortion 392 had nausea 248 had vomiting 259 had fever 272 had headache 418 had chills and 398 had fatigue The investigators do not expect the side effects to be substantially different Previously the mean pain scores were 63 on an 11-point pain scale
Medical abortions induced with either mifepristone or methotrexate and then followed by misoprostol are becoming more common Although mifepristone is the preferred drug used to initiate the abortion in Europe parts of Asia and in the US it is not available in many parts of the world such as Canada South America and most of Africa While methotrexate is an acceptable and more widely available alternative concerns about the safety of administration have discouraged some providers from using it The cost of either mifepristone or methotrexate may also be barriers to widespread use Misoprostol is inexpensive and easily available and is used alone for abortion both by the women themselves and by medical providers Effective use of a single safe medication will reduce the number of medications women are exposed to
Reported effectiveness rates for misoprostol alone in terminating pregnancies less than 8 weeks range from 64 to 94 with varying doses and protocols Use of misoprostol in early pregnancy is associated with an increased risk of Mobius syndrome in infants For this reason it is important that the most effective regimen is used for abortion to prevent failures
A summary of the published protocols and results are as follows A rate of 913 was found using 800 mcg vaginally every 24 hours for three doses with higher effectiveness before 42 days gestation A dose of 400 mcg sublingual misoprostol repeated every 24 hours for three doses resulted in 86 success When mifepristone followed by 400 mcg misoprostol orally was compared to 800 mcg misoprostol vaginally the effectiveness rate of the misoprostol alone was 88 and there were more prostaglandin side effects compared to the combined drug regimen These side effects were reduced with prophylactic acetominophen and loperamide Another centre reported a 908 effectiveness rate with two doses of 800 mcg misoprostol vaginally One study assessed women after each dose of 800 mcg vaginal misoprostol and found that only 718 aborted after one dose and 921 aborted after multiple doses When 800 mcg vaginally was repeated every 48 hours for three doses an effectiveness rate of 936 was obtained The same rate was obtained using 1000 mcg When only 600 mcg vaginally was used the effectiveness rate was only 64 repeating the dose every 8 hours did not improve the effectiveness Similar rates were found for adolescents
One proposed hypothesis for the 64-94 range in effectiveness between these various protocols is that sublingual misoprostol has a higher peak serum concentration than oral or vaginal misoprostol In other words the mean time to peak concentration for sublingual misoprostol is similar to oral misoprostol at 26 minutes and the area under the MPA curve is similar to moistened vaginal misoprostol
The regimen planned for this study is a one-step procedure reported at the International Consortium for Medical Abortion meeting in Johannesburg October 2004 by Iheoni Obineche He reported a series of 80 cases in which 79 988 aborted within 12 hours of receiving 400 mcg vaginal misoprostol after a thorough vaginal cleanse plus 400 mcg sublingual misoprostol administered at the same time This will be compared to the standard protocol based on the National Abortion Federation and SOGC which is 50mgm2 of methotrexate injected intramuscularly followed by misoprostol 800mcg per vaginal 4-7 days later
Rationale
In countries where abortion is illegal and common such as those in Africa and South America it is important to find a regimen using misoprostol alone which has a higher completion rate than those regimens usually used
Trial Objectives
The primary objective of this study is to determine if misoprostol alone using this regimen is as effective as the investigators current practice of methotrexate followed by misoprostol for early abortion The secondary objectives are to compare side effects and to assess acceptability
Study Design and Duration
This is a randomized controlled open-label trial Women requesting medical termination of pregnancy at 7 weeks gestation or less will be recruited
The study protocol risks benefits visit schedule and consent will be reviewed with each potential subject The informed consent will include the statement if the treatment does not work I have been advised to agree to a surgical abortion A haemoglobin and Rh factor will be obtained and reviewed A focussed history and physical examination will be performed Gestational dating will be done by endovaginal ultrasound using the following criteria gestational age days mean sac diameter mm 30 or embryonic pole mm 42 Mean sac diameter is used only if there is no embryonic pole This method has been described by Rossavik and Goldstein
Randomization will be performed by using a computer generated list of block random numbers and sealed numbered opaque envelopes will be prepared by a staff member not involved in the informationconsent process
In both groups women who are Rh negative will receive 120 g RhD immune globulin on Day 1 The methotrexatemisoprostol group will be given 50 mgm2 methotrexate and both written and oral instructions At least 72 hours after the methotrexate Day 4-7 they will be asked to moisten four 200 g tablets of misoprostol with a few drops of water each and insert them into the vagina On Day 1 the misoprostol-only group will receive 400 g misoprostol sublingually and the doctor will use a speculum and warm water to cleanse the vagina moisten 400 g misoprostol with warm water and place it in the vaginal fornices All women will also be given six tablets of acetaminophen with codeine two tablets of diphenhydramine and six tablets of 400 mg ibuprofen to use for side effects
All subjects will return to the office within 7 days of having the misoprostol and have another vaginal ultrasound If they have not aborted they will be offered three options waiting using additional doses of misoprostol or surgery If the abortion is failed as evidenced by embryonic cardiac activity on Day 15 these women will be scheduled for surgical aspiration At the first follow-up visit information will be obtained about completion of the abortion and then about the womans experience of bleeding pain and side effects Pain will be measured by an 11-point numeric pain scale using the question On a scale of 0 to 10 where 0 is no pain and 10 is pain as bad as it can be what was the worst pain like for you They will be asked If you were in the same situation would you choose a medical or surgical abortion If given the choice would you choose the same medications you received in this study These scales and questions have been reported in other studies
The main outcome measure is effectiveness after the first dose of misoprostol measured by the number of abortions completed at the first follow-up visit The investigators will also compare the rate of surgery the time taken to abort based on history side effects pain and satisfaction Previous studies have had about 86 of women prefer a medical abortion 392 had nausea 248 had vomiting 259 had fever 272 had headache 418 had chills and 398 had fatigue The investigators do not expect the side effects to be substantially different Previously the mean pain scores were 63 on an 11-point pain scale
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None