Mifepristone + Misoprostol for Second Trimester Miscarriage

(MIST Trial)

No longer recruiting at 1 trial location

Overseen By Katherine H Bligard, MD,MA

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Washington University School of Medicine

Disqualifiers: Contraindication to mifepristone, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 24-48 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining mifepristone (a medication used to induce labor) with misoprostol is more effective than using misoprostol alone for inducing labor in the second trimester when a pregnancy is not viable. The goal is to determine if this combination can reduce labor time, potentially lowering the risk of complications for the mother. It targets women who are between 14 and 28 weeks pregnant with a nonviable fetus and require labor induction. As a Phase 4 trial, this research aims to understand how the already FDA-approved treatment benefits more patients.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications.

What is the safety track record for mifepristone and misoprostol?

Research has shown that using mifepristone and misoprostol together is generally safe for early pregnancy loss. These medications have been effective for pregnancies up to 12 weeks. Studies indicate that misoprostol often induces labor in the second trimester without reports of serious infections. However, rare but serious complications can occur when using mifepristone and misoprostol in the second trimester.

The FDA closely monitors the safety of mifepristone. Some studies have highlighted potential significant risks, though these are uncommon. Prospective trial participants should understand the possible risks and benefits of these medications. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of mifepristone and misoprostol for managing second trimester miscarriage because it offers a potentially more effective approach than misoprostol alone, which is the current standard of care. Mifepristone works by preparing the uterus and enhancing the effectiveness of misoprostol, which induces labor. This combination could lead to faster and more complete miscarriage management, reducing the emotional and physical burden for patients. By improving the efficiency of the process, this treatment approach aims to offer a better overall experience for those undergoing this difficult medical event.

What evidence suggests that this trial's treatments could be effective for second trimester miscarriage?

This trial will compare two treatment approaches for inducing labor in the second trimester. One group of participants will receive misoprostol alone, while another group will receive a combination of mifepristone and misoprostol. Research has shown that using mifepristone with misoprostol effectively starts labor in the second trimester. This combination speeds up the process, which can be crucial in certain situations. Studies indicate that a 200 mg dose of mifepristone is as effective as higher doses when used with misoprostol. This combination is known for its effectiveness and ability to accelerate labor. Both medications are considered safe and effective when used together, especially when time is critical. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are between 14 and 28 weeks pregnant with a single nonviable fetus, meaning the fetus has passed away or cannot survive due to its gestational age/weight or a fatal condition.

Inclusion Criteria

I am between 14 and 28 weeks pregnant.

You are pregnant with only one baby.

The baby in your womb is no longer alive or has a condition that makes survival impossible.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either misoprostol alone or simultaneous mifepristone and misoprostol for induction of labor

24-48 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after induction of labor

During admission

What Are the Treatments Tested in This Trial?

Interventions

• Mifepristone
• Misoprostol

Trial Overview

The study is testing if taking Mifepristone and Misoprostol at the same time offers any benefits compared to just Misoprostol alone in inducing labor when dealing with a nonviable second trimester pregnancy.

How Is the Trial Designed?

Group I: Simulatenous mifepristone and misoprostol Experimental Treatment 2 Interventions

Participants will receive a dose of 200mg oral mifepristone at time of induction with misoprostol

Group II: Misoprostol alone Active Control 1 Intervention

Participants will have labor induced with misoprostol alone

Mifepristone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Mifeprex for:

• Abortion
• Cushing's Syndrome

Approved in European Union as Mifegyne for:

• Abortion
• Cushing's Syndrome

Approved in Canada as Mifeprex for:

• Abortion
• Cushing's Syndrome

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Mifepristone combined with misoprostol (MM) has a lower failure rate for second-trimester abortion (2.0% to 5.9%) compared to ethacridine lactate (EL) (7.4% to 20.7%), indicating higher efficacy for MM.

The MM method also results in shorter labor and hospitalization times, although it is associated with more gastrointestinal side effects, while EL is linked to a higher incidence of cervical injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Termination of second-trimester pregnancy by mifepristone combined with misoprostol versus intra-amniotic injection of ethacridine lactate (Rivanol®): a systematic review of Chinese trials. Hou, SP., Fang, AH., Chen, QF., et al.[2018]

In a study of 270 women, vaginal administration of misoprostol after mifepristone resulted in a higher success rate for abortion without surgical intervention (95% vs. 87% for oral administration), indicating greater efficacy of the vaginal route.

Vaginal misoprostol also led to faster abortions, with 93% of women aborting within four hours compared to 78% with the oral route, and it had fewer side effects like vomiting and diarrhea, making it a better-tolerated option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. el-Refaey, H., Rajasekar, D., Abdalla, M., et al.[2013]

In a study of 99 patients, the method of using mifepristone and misoprostol for pregnancy termination or intrauterine fetal death resulted in a high delivery rate within 24 hours (96% for fetal death and 92% for termination).

The median duration of treatment was longer for intrauterine fetal death (10 hours) compared to pregnancy termination (8 hours), but overall complication rates and side effects were consistent with previous studies, indicating the method's safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of pregnancy termination for foetal congenital or chromosomal disorders or intrauterine foetal death by oral mifepristone and/or intravaginal misoprostol; results of a retrospective study]. Verhulsdonk, MT., Papatsonis, DN., Heydanus, R.[2013]

RU486 (mifepristone) combined with a prostaglandin analogue has a high efficacy rate of 95.3% for early pregnancy termination, with a slight increase to 96.9% when followed by misoprostol, indicating it is a reliable medical alternative to surgical procedures.

While the treatment is generally safe, there are potential side effects and serious adverse events, including a fatality, which necessitate careful medical monitoring for several hours after administration of the prostaglandin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RU486: the French experience. Ulmann, A., Silvestre, L.[2019]

In a study of 70 women, the combination of mifepristone and misoprostol achieved a 97% success rate for inducing second trimester abortion, demonstrating high efficacy without the need for additional prostaglandin agents.

The average time from induction to abortion was 6.4 hours, and no significant differences were found between vaginal and combined vaginal/oral administration routes, suggesting flexibility in how misoprostol can be administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of abortion in the second trimester by a combination of misoprostol and mifepristone: a randomized comparison between two misoprostol regimens. el-Refaey, H., Templeton, A.[2019]

In a study of 133 samples of early abortions induced by mifepristone (RU486) and misoprostol (Miso), no significant differences were found in outcomes or pathological changes between different dosages of the drugs.

The villi from the RU486-Miso group exhibited more severe degeneration compared to control samples from vacuum aspiration, suggesting a potential impact of RU486 on trophoblasts, although the exact mechanism remains unclear and requires further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The pathological investigations on termination of early pregnancy with mifepristone]. Liu, B., Sun, J., Tao, W.[2013]

Combining mifepristone with misoprostol significantly shortens the induction-abortion interval in second-trimester abortions, as shown in a study of 60 patients, which helps reduce side effects and hospital stay duration.

The study supports the safety and efficacy of this combination treatment, making it a reliable and cost-effective option for elective abortions between 13 and 20 weeks of gestation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-induction with Mifepristone for Second Trimester Termination of Pregnancy. Kulkarni, KK.[2021]

In a study of 62 patients undergoing medical termination of early pregnancy with mifepristone (RU 486) and a prostaglandin analogue, the method achieved a high success rate of 97%.

The procedure had rare side effects, although about half of the patients required strong analgesics, indicating that while effective, pain management is an important consideration during the process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Reintroduction of medical abortion in Denmark]. Olsen, CD., Wittendorff, HE., Jørgensen, JJ.[2014]

A case study of a 30-year-old woman who had a second-trimester abortion after a previous cesarean delivery revealed a rare but serious complication: vesicouterine rupture, where the fetus escaped into the bladder.

The case emphasizes the need for close monitoring of patients with prior cesarean sections during medical abortions, as early detection of complications can lead to successful conservative surgical management and preservation of fertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined vesicouterine rupture during second-trimester medical abortion for fetal abnormality after prior cesarean delivery: A case report. Caruso, G., Paladini, V., D'ambrosio, V., et al.[2022]

In a study of 50 women undergoing second trimester pregnancy termination, misoprostol was found to be as effective as gemeprost when used with mifepristone, with no significant difference in the time it took for the abortion to occur (8.7 hours for misoprostol vs. 10.8 hours for gemeprost).

Both medications resulted in similar side effects, indicating that misoprostol is a safe alternative to gemeprost for this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone: a randomised comparative trial. Ho, PC., Chan, YF., Lau, W.[2014]

A combined regimen of mifepristone and misoprostol is significantly more effective than misoprostol alone for inducing complete expulsion in first trimester abortions, with a risk ratio of 1.19 based on a meta-analysis of 9 studies involving 2,052 participants.

This combined treatment not only reduces the likelihood of incomplete abortions and ongoing pregnancies but also shows a lower incidence of fever, although it may lead to increased subjective bleeding experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of mifepristone plus misoprostol with misoprostol alone for first trimester medical abortion: A systematic review and meta-analysis. Shimels, T., Getnet, M., Shafie, M., et al.[2023]

Pretreatment with mifepristone significantly increases the likelihood of complete uterine evacuation within 15 hours compared to misoprostol alone, with a relative risk of 2.16 (79.8% vs. 36.9%).

The time from induction to abortion is shorter for women who received mifepristone (8.1 hours) compared to those who only received misoprostol (10.6 hours), while both treatments have similar side-effect profiles and high acceptability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mifepristone and misoprostol compared with misoprostol alone for second-trimester abortion: a randomized controlled trial. Ngoc, NTN., Shochet, T., Raghavan, S., et al.[2021]

In a study involving 35 patients, mifepristone (RU486) was safely administered for therapeutic interruption of pregnancy, with no recorded toxicity or maternal morbidity.

Mifepristone effectively modified cervical consistency, improving cervical calibration regardless of the dose used (150 mg or 450 mg), which may facilitate the labor process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mifepristone (RU486) and therapeutic late pregnancy termination: a double-blind study of two different doses. Frydman, R., Fernandez, H., Pons, JC., et al.[2019]

Citations

1.

aafp.org

aafp.org/pubs/afp/issues/2021/0415/p473.html

Mifepristone and Misoprostol for Early Pregnancy Loss ...

Medication regimens using mifepristone and misoprostol are safe and effective for outpatient treatment of early pregnancy loss for up to 84 days' gestation.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7484538/

Medical regimens for abortion at 12 weeks and above

One trial with 70 subjects compared 200 mg vs. 600 mg of mifepristone before misoprostol (Supplements 6C and 7C) [35]. We found no differences in any outcomes.

3.

societyfp.org

societyfp.org/wp-content/uploads/2023/11/SFP_Clinical-Recommendation_Medication-abortion-between-14-0.7-and-27-6.7-weeks-of-gestation_2023_Final.pdf

SFP_Clinical-Recommendation_Medication-abortion- ...

Mifepristone dose. Mifepristone 200 mg is as effective as 600 mg when used in a combination with misoprostol [14]. In a randomized controlled trial (RCT) of ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S1028455911001240

The use of misoprostol in termination of second-trimester ...

For termination of second-trimester pregnancy, using the combination of mifepristone and misoprostol seems to have the highest efficacy and shortest abortion ...

5.

acog.org

acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/10/medication-abortion-up-to-70-days-of-gestation

Medication Abortion Up to 70 Days of Gestation

Adverse effects commonly associated with misoprostol use include nausea (43–66%), vomiting (23–40%), diarrhea (23–35%), headache (13–40%), dizziness (28–39%), ...

6.

fda.gov

fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questions-and-answers-mifepristone-medical-termination-pregnancy-through-ten-weeks-gestation

Questions and Answers on Mifepristone for Medical ...

As with all drugs, the FDA continues to closely monitor the postmarketing safety data on mifepristone for the medical termination of pregnancy.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC1785176/

Mifepristone-Misoprostol Medical Abortion Mortality - PMC

Moreover, vaginal misoprostol is used routinely for labor induction and second-trimester labor-induction abortion without any reports of serious infection with ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0010782423001609

Maternal complications associated with second trimester ...

Second trimester medical abortion with mifepristone and misoprostol is generally safe, however, on occasions serious complications may occur.

9.

amnionpregnancycenter.com

amnionpregnancycenter.com/new-study-on-the-abortion-pill-reveals-significant-risks-to-women/

NEW Study on The Abortion Pill Reveals Significant Risks ...

A new study based on actual medical insurance claims has uncovered crucial data about the risks women have experienced after taking these pills.